| 1. |
- Bondesson, Susanne, et al.
(författare)
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Comparison of patients undergoing enhanced external counterpulsation and spinal cord stimulation for refractory angina pectoris.
- 2008
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Ingår i: Coronary Artery Disease. - 0954-6928. ; 19:8, s. 627-634
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: As more patients survive coronary events, the prevalence of patients with refractory angina pectoris is increasing. The aim was to evaluate the effects of enhanced external counterpulsation (EECP) and spinal cord stimulation (SCS) and compare with optimal medically treated patients with refractory angina. METHODS: 153 patients with refractory angina were treated with either EECP, SCS, or were retained on their pharmacological treatment (control). Glyceryl trinitrate usage and Canadian Cardiovascular Society classification were registered at baseline, 6 and 12 months after therapy. RESULTS: Both EECP and SCS reduced the angina as compared with controls (P<0.001). Patients treated with EECP showed a more effective reduction as compared with SCS patients (P<0.05). Both treatments resulted in significantly decreased glyceryl trinitrate usage at 6 and 12 months follow-up (P<0.001). The nitrate consumed was unaltered in the controls. DISCUSSION: The results from this study show that both EECP and SCS therapy reduce angina in patients with refractory angina pectoris; the response to EECP was slightly more effective than that to SCS. Thus, EECP can be used as an alternative treatment for patients not responding to electrical stimulation. The beneficial effects in the treated groups were maintained during the 12 months follow-up period.
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| 2. |
- Bondesson, Susanne, et al.
(författare)
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Effects on blood pressure in patients with refractory angina pectoris after enhanced external counterpulsation
- 2010
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 19:5, s. 287-294
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Enhanced external counterpulsation (EECP) is a non-invasive technique that has been shown to reduce the frequency and severity of angina pectoris. Little is known how EECP affects the blood pressure. Methods. 153 patients with refractory angina were treated with either EECP or retained on their pharmacological treatment (reference group). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP) and heart rate were measured pre- and post-treatment and at 12 months follow-up. Results. EECP treatment altered the blood pressure in patients with refractory angina pectoris. A decrease in the blood pressure was more common in the EECP group compared with the reference group. In the reference group, an increase in the blood pressure was more common. A correlation between a decrease in blood pressure after EECP treatment and a higher baseline MAP, SBP and DBP was seen. No such correlation was seen in the reference group. The blood pressure response did not persist at 12 months follow-up. Conclusion. EECP treatment affects the blood pressure in patients with refractory angina pectoris. The decreased blood pressure may be a result of an improved exercise capacity, an improved endothelial function and vasoreactivity in general.
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| 3. |
- Edvinsson, Lars, et al.
(författare)
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Triptan-induced contractile (5-HT1B receptor) responses in human cerebral and coronary arteries: relationship to clinical effect
- 2005
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Ingår i: Clinical Science. - 1470-8736. ; 109:3, s. 335-342
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Tidskriftsartikel (refereegranskat)abstract
- Triptans are agonists at 5-HT1B and 5-HT1D (where 5-HT is 5-hydroxytryptamine; serotonin) receptors and cause vasoconstriction of isolated blood vessels. The aim of the present study was to determine vasoconstrictor potency (EC50) of triptans in human coronary and cerebral arteries and to examine whether there was any relationship with the maximal plasma concentrations (Cmax; nM) of the drugs achieved following oral administration of clinically relevant doses to man using values reported in the literature. We also examined the expression of 5-HT1B receptors in atherosclerotic and normal coronary arteries. The vasocontractile responses to sumatriptan, rizatriptan or eletriptan were characterized by in vitro pharmacology. The ratio of Cmax/EC50 was calculated. 5-HT1B and 5-HT1D receptors were visualized by immunohistochemical techniques in coronary arteries. Sumatriptan, rizatriptan and eletriptan were powerful vasoconstrictors in cerebral artery. The rank order of agonist potency was eletriptan = rizatriptan = sumatriptan. In the coronary artery, the triptans were weaker vasoconstrictors. The rank order of potency was similar. In cerebral artery the ratio of Cmax/EC50 was not significantly different from unity, indicating a relationship between these two parameters. In general for the coronary artery, the ratios were significantly less than unity, indicating no direct relationship. Immunohistochemistry showed expression of 5-HT1B receptors in the medial layer, but did not reveal any obvious difference in 5-HT1B receptor expression between normal and atherosclerotic coronary arteries. The results support the notion that triptans are selective vasoconstrictors of cerebral arteries over coronary arteries and that there is a relationship between vasoconstrictor potency in cerebral arteries and clinically relevant plasma levels.
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| 4. |
- Gesslein, Bodil, et al.
(författare)
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Protein kinase C in porcine retinal arteries and neuroretina following retinal ischemia-reperfusion.
- 2009
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Ingår i: Molecular Vision. - 1090-0535. ; 15:Apr 13, s. 737-746
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Identification of the intracellular signal-transduction pathways activated in retinal ischemia may be important in revealing novel pharmacological targets. To date, most studies have focused on identifying neuroprotective agents. The retinal blood vessels are key organs in circulatory failure, and this study was therefore designed to examine the retinal vasculature separately from the neuroretina. METHODS: Retinal ischemia was induced by elevating the intraocular pressure in porcine eyes, followed by 5, 12, or 20 h of reperfusion. Protein kinase C (PKC)alpha, PKCbeta1, and PKCbeta2 mRNA levels, and protein expression were determined using real-time PCR, western blot, and immunofluorescence staining techniques. RESULTS: The retinal arteries could easily be dissected free and studied separately from the neuroretina in this porcine model. The PKCalpha, PKCbeta1, and PKCbeta2 mRNA levels tended to be lower in ischemia-reperfused than in sham-operated eyes in both the retinal arteries and the neuroretina. This was most prominent after 5 h, and less pronounced after 12 h and 20 h of reperfusion. Likewise, the protein levels of PKCalpha, PKCbeta1, and PKCbeta2 were slightly lower following ischemia-reperfusion when compared to sham-operated eyes. PKCalpha, PKCbeta1, and PKCbeta2 immunostaining were observed in bipolar cells of the neuroretina and in endothelial cells, and to a low extent in the smooth muscle layer, of the retinal arteries. CONCLUSIONS: Retinal ischemia followed by reperfusion results in lower levels of PKC in both the neuroretina and retinal arteries. New targets for pharmacological treatment may be found by studying the retinal vasculature so as to identify the intracellular signal-transduction pathways involved in the development of injury following retinal circulatory failure.
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| 5. |
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| 6. |
- Johnsson, Evelina, et al.
(författare)
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Enhanced expression of contractile endothelin ET(B) receptors in rat coronary artery after organ culture.
- 2008
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 582:1-3, s. 94-101
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Tidskriftsartikel (refereegranskat)abstract
- Endothelin-1 is a potent vasoconstrictor mediating its effects via two receptor subtypes, the endothelin type A (ET(A)) preferentially situated on smooth muscle cells, mediating vasoconstriction and endothelin type B (ET(B)) mainly located on endothelial cells, mediating vasodilatation. In cardiovascular disease and in organ culture in vitro, endothelin ET(B) receptors are up-regulated on smooth muscle cells. The objectives of the present study were to characterise the endothelin receptor-induced vasoconstriction and quantify the endothelin receptor mRNA levels and immunoreactivity in fresh and cultured rat coronary arteries. We demonstrate that endothelin-1 induces strong and equal concentration-dependent contractions in fresh and cultured segments from the left anterior descending coronary artery. Sarafotoxin 6c, an endothelin ET(B) receptor agonist, had negligible effect in fresh arteries but produced significant vasoconstriction after organ culture. The endothelin ET(B) receptor mRNA level and the receptor protein immunoreactivity were increased, whereas the level of endothelin ET(A) receptor mRNA was down-regulated but not its receptor protein immunoreactivity after organ culture. Pharmacological inhibition of endothelium-derived dilatory mediators did not influence endothelin ET(A) or ET(B) receptor-mediated vasoconstriction in fresh segments. In cultured arteries, inhibition of endothelial vasodilators potentiated the effect of sarafotoxin 6c. In conclusion, endothelin ET(B) receptor stimulation in cultured coronary arteries elicits vasoconstriction. This is likely not related to endothelial dysfunction with putative loss of its vasodilator components, but rather explained by the up-regulation of contractile endothelin ET(B) receptors on smooth muscle cells.
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| 7. |
- Nilsson, David, et al.
(författare)
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Endothelin receptor-mediated vasodilatation: Effects of organ culture.
- 2008
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 579:1-3, s. 233-240
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Tidskriftsartikel (refereegranskat)abstract
- Culture of intact arteries is a frequently employed experimental model for investigating the mechanisms governing the regulation of vascular endothelin receptors. Endothelin type A (ETA) and type B (ETB) receptors on vascular smooth muscle cells are up-regulated in organ culture and the enhanced vasoconstriction mimics the changes that occur in cardiovascular disease. The effect of organ culture on endothelial dilatory endothelin ETB receptors is not known. We hypothesize that organ culture decreases the endothelin receptor-mediated dilatation and that this is one possible mechanism by which the effects of the endothelin in blood vessels are altered during culture. Porcine coronary arteries were studied before and after 24 h of culture, using in vitro pharmacology and immunofluorescence. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ETA and ETB receptor effects, and the antagonists, Nω-nitro-l-arginine (l-NOARG) for nitric oxide (NO), indomethacin for prostaglandins and charybdotoxin in combination with apamin for endothelium-derived hyperpolarizing factor (EDHF), were used to study the endothelium-derived dilatory mediators. Organ culture induced up-regulation of the sarafotoxin 6c (ETB receptor agonist) and endothelin-1 (ETA receptor agonist) elicited vasoconstriction. The sarafotoxin 6c contraction was stronger after endothelium denudation, suggesting endothelium-dependent dilatation. The endothelin-1 contraction was not affected by endothelium denudation. The increase in sarafotoxin 6c contraction after removal of the endothelium was more pronounced before than after organ culture, suggesting down-regulated endothelial endothelin ETB receptors. Also, the immunofluorescence staining intensities for endothelial endothelin ETB receptors were higher before than after organ culture. Pre-incubation with inhibitors for dilatory mediators suggested that both NO and EDHF play a vasodilatory role, while prostaglandins are not involved. In conclusion, endothelial endothelin ETB receptors induce NO and EDHF mediated vasodilatation in porcine coronary arteries. In organ culture, endothelial endothelin ETB receptors are down-regulated, mimicking the changes that occur in cardiovascular disease. Down-regulation of endothelial endothelin ETB receptors may in part explain the increased endothelin ETB receptor-mediated vasoconstriction frequently studied in organ culture.
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| 8. |
- Nilsson, David, et al.
(författare)
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Increased ET(A) and ET(B) receptor contraction in the left internal mammary artery from patients with hypertension.
- 2008
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Ingår i: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 1476-5527 .- 0950-9240. ; 22:3, s. 226-229
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Tidskriftsartikel (refereegranskat)abstract
- Patients with hypertension have an increased activity in the endothelin system and an increased vascular tone, which predisposes them to target organ damage. In the present study, in vitro pharmacology, real-time PCR and immunofluorescence techniques were used to show enhanced endothelin type A (ETA) and type B (ETB) receptor contraction and expression in the left internal mammary artery from patients with hypertension as compared to normotensive patients. These receptors may be important in the pathophysiology of hypertension.
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| 9. |
- Nilsson, David, et al.
(författare)
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PKC and MAPK signalling pathways regulate vascular endothelin receptor expression
- 2008
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 580:1-2, s. 190-200
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Tidskriftsartikel (refereegranskat)abstract
- Up-regulation of vascular endothelin type A (ET(A)) and type B (ET(B)) receptors are implicated in the pathogenesis of cardiovascular disease. Culture of arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for in detail delineation of the regulation of endothelin receptors. We hypothesize that protein kinase C (PKC) and mitogen-activated kinases (MAPK) are involved in the regulation of endothelin receptors. Porcine coronary arteries were studied before and after 24 h of culture, using in vitro pharmacology, real-time PCR and immunofluorescence techniques. Sarafotoxin 6c and endothelin ET-1 were used to examine the endothelin ET(A) and ET(B) receptor effects. The involvement of PKC and MAPK in the receptor regulation was examined by culture in the presence of antagonists. Organ culture resulted in increased sarafotoxin 6c and endothelin-1 contractions, endothelin ET(A) and ET(B) receptor immunofluorescence staining intensities and endothelin ET(B), but not ET(A), receptor mRNA levels. The general PKC inhibitors, bisindolylmaleimide I (10 muM) or Ro-32-0432 (10 muM), inhibited these effects. Also, the increase in sarafotoxin 6c contraction, endothelin ET(B) receptor and mRNA levels and endothelin ET(A) and ET(B) immunofluorescence staining intensities were inhibited by MAPK inhibitors for extracellular signal related kinases 1 and 2 (ERK1/2), PD98059 (10 muM), C-jun terminal kinase (JNK), SP600125 (10 muM), but not by p38 MAPK, SB203580 (10 muM). In conclusion, PKC and MAPK seem to be involved in the regulation of endothelin receptor expression in porcine coronary arteries. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin receptor changes in cardiovascular disease.
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| 10. |
- Nilsson, David, et al.
(författare)
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Up-regulation of endothelin type B receptors in the human internal mammary artery in culture is dependent on protein kinase C and mitogen-activated kinase signaling pathways.
- 2008
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Up-regulation of vascular endothelin type B (ETB) receptors is implicated in the pathogenesis of cardiovascular disease. Culture of intact arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for, ex vivo, in detail delineation of the regulation of endothelin receptors. We hypothesize that mitogen-activated kinases (MAPK) and protein kinase C (PKC) are involved in the regulation of endothelin ETB receptors in human internal mammary arteries. METHODS: Human internal mammary arteries were obtained during coronary artery bypass graft surgery and were studied before and after 24 hours of organ culture, using in vitro pharmacology, real time PCR and Western blot techniques. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ETA and ETB receptor effects, respectively. The involvement of PKC and MAPK in the endothelin receptor regulation was examined by culture in the presence of antagonists. RESULTS: The endohtelin-1-induced contraction (after endothelin ETB receptor desensitization) and the endothelin ETA receptor mRNA expression levels were not altered by culture. The sarafotoxin 6c contraction, endothelin ETB receptor protein and mRNA expression levels were increased after organ culture. This increase was antagonized by; (1) PKC inhibitors (10 microM bisindolylmaleimide I and 10 microM Ro-32-0432), and (2) inhibitors of the p38, extracellular signal related kinases 1 and 2 (ERK1/2) and C-jun terminal kinase (JNK) MAPK pathways (10 microM SB203580, 10 microM PD98059 and 10 microM SP600125, respectively). CONCLUSION: In conclusion, PKC and MAPK seem to be involved in the up-regulation of endothelin ETB receptor expression in human internal mammary arteries. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin ETB receptor changes in cardiovascular disease.
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| 11. |
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| 12. |
- Samuelsson, Anders, 1960-, et al.
(författare)
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Serotonin kinetics in patients with burn injuries : A comparison between the local and systemic responses measured by microdialysis-A pilot study
- 2008
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Ingår i: Burns. - : Elsevier BV. - 0305-4179 .- 1879-1409. ; 34:5, s. 617-622
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate serotonin (5HT) locally in burned and uninjured skin (intracutaneous) by microdialysis, and simultaneously record urinary and blood values in the same subjects. For comparison, serotonin values were also measured in skin of healthy controls. Design and setting: An experimental study in burned patients with of more than 25% TBSA (total burn surface area) % in an 8-bed tertiary burns unit, serving about 3.5 million persons. Patients and methods: Six subjects with a median TBSA% of 59% (range 33.5-90), and five healthy controls were examined by intracutaneous microdialysis of the skin. Results: 5HT was increased in burned patients, compared with controls. This increase was tenfold in skin and was noted both in uninjured and burned skin. The highest values were recorded on day 1 (median 16.1 nmol in uninjured and 9.5 nmol in burned skin) and day 2 (15.6 nmol in uninjured and 13.4 nmol in burned skin). A rapid reduction was noted on day 3 (4.9 nmol in uninjured and 3.8 nmol in burned skin). The corresponding value for control subjects was 1.3 nmol. The 5HT in blood was twice normal on day 2, and gradually reduced on days 3 and 4 (3189, 3035 and 2573 nmol, respectively). Urinary 5HT concentrations were increased only on day 2 at 1755 nmol and thereafter returned to the normal range on days 3 and 4 (1248 and 1344 nmol, respectively). Conclusions: We showed that microdialysis may be used in the critical care of burns, and local skin serotonin concentrations examined continuously for several days. The findings of significantly raised tissue serotonin concentrations, compared to that in blood and urine, suggests that serotonin may be important in local vascular control and formation of oedema. © 2007 Elsevier Ltd and ISBI.
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| 13. |
- Sjögren, Johan, et al.
(författare)
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Effects of vacuum-assisted closure on central hemodynamics in a sternotomy wound model
- 2004
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Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293. ; 3:4, s. 666-671
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Tidskriftsartikel (refereegranskat)abstract
- Several authors have reported promising results with vacuum-assisted closure therapy in poststernotomy mediastinitis. The aim of this study was to investigate the hemodynamic outcome following the application of six negative pressures on an open sternotomy wound. Six 70-kg pigs underwent median sternotomy followed by vacuum-assisted closure therapy. Six negative pressures (-50, -75, -100, -125, -150, and -175mmHg) were applied to each pig for 30min each while hemodynamic parameters were measured. An increase in cardiac output was observed at -75mmHg when compared to the other five pressures: -50mmHg (P<0.05; CI 0.12-1.13l/min), -100mmHg (P<0.001; CI 0.34-1.32l/min), -125mmHg (P<0.001; CI 0.51-1.52l/min), -150mmHg (P<0.001; CI 0.50-1.47l/min), and -175mmHg (P<0.05; CI 0.13-1.17l/min). A decrease in systemic vascular resistance was observed at -75mmHg when compared to -125mmHg (P<0.01; CI 108-552dyn.s/cm(5)) and -150mmHg (P<0.01; CI 90-543dyn.s/cm(5)), but not compared to the other pressures. No change (P=ns) was observed in heart frequency, mean arterial pressure or central venous pressure. Our data demonstrates that vacuum-assisted closure therapy of -50 to -175mmHg does not impair the central hemodynamics in a porcine sternotomy model.
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| 14. |
- Torbrand, Christian, et al.
(författare)
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Sympathetic and sensory nerve activation during negative pressure therapy of sternotomy wounds.
- 2008
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Ingår i: Interactive cardiovascular and thoracic surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293. ; 7:6, s. 1067-70
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Tidskriftsartikel (refereegranskat)abstract
- Negative pressure wound therapy (NPWT) has been adopted as the first-line treatment for poststernotomy mediastinitis as a result of the excellent clinical outcome. The knowledge concerning the effects of NPWT on the cardiovascular system and homeostasis is still limited. The aim of the present study was to investigate whether the plasma levels of neurohormones change during NPWT. Six pigs underwent median sternotomy followed by NPWT at -125 mmHg. The plasma levels of noradrenaline, adrenaline, neuropeptide Y, substance P, vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP) were determined before (0 min) and 5, 20, 60 and 180 min after the application of NPWT. The results show a transient increase in the plasma levels of noradrenaline and adrenaline when NPWT was applied. The plasma level of the adrenergic co-transmitter neuropeptide Y was higher in NPWT--than in sham-treated pigs, after 180 min of negative pressure. After 180 min of NPWT there was an increase in the plasma levels of the sensory nerve transmitter substance P, while no such effect was observed for CGRP or VIP. In conclusion, the results suggest sympathetic nerve activation during NPWT. This may be the result of an increase in workload on the heart during the initial phase of NPWT.
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| 15. |
- Wackenfors, Angelica, et al.
(författare)
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Angiotensin II-induced vasodilatation in cerebral arteries is mediated by endothelium-derived hyperpolarising factor.
- 2006
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 531:1-3, s. 259-263
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Tidskriftsartikel (refereegranskat)abstract
- The angiotensin II-induced vasodilatation was evaluated in rat middle cerebral artery, especially regarding endothelium-derived hyperpolarising factor (EDHF), by use of a pressurised arteriograph. The angiotensin II dilatation was partly antagonised by inhibitors of nitric oxide synthase and cyclo-oxygenase. The remaining dilatation was inhibited by the potassium channel blockers, charybdotoxin and apamin, providing direct evidence that angiotensin II induces EDHF-mediated dilatation in cerebral arteries. The angiotensin II dilatation was blocked by the angiotensin AT(1) and AT(2) receptor blockers candesartan and PD 123319. Both angiotensin AT(1) and AT(2) receptors were detected on the endothelium by imnitmohistochemistry. (c) 2005 Elsevier B.V. All rights reserved.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Wackenfors, Angelica
(författare)
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Endothelin and angiotensin II receptors in human coronary arteries and bypass grafts - Alterations in cardiovascular disease
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Angiotensin II (Ang II) and endothelin-1 (ET-1) induce strong vasoconstriction via activation of receptors on vascular smooth muscle cells. In this thesis, the contractile Ang II and endothelin receptors were examined in endothelium-denuded human coronary arteries and in bypass grafts (the left internal mammary artery and the saphenous vein), with focus on receptor alterations in cardiovascular disease. The endothelium was removed and the vasomotor responses were characterized by in vitro pharmacology and the receptor mRNA expression levels were quantified by real-time polymerase chain reaction. Vasoconstriction was mediated by endothelin type A (ETA) receptors in coronary arteries, while both ETA and endothelin type B (ETB) receptors were involved in the bypass grafts. The ETB receptor-mediated contraction and mRNA levels were higher in the saphenous vein than in the mammary artery. This may explain the higher frequency of vasospasm that is seen in the vessel wall of the saphenous vein at the time of surgery and restenosis due to “venous graft disease”. The ETA and ETB receptor mRNA levels were up-regulated in coronary arteries from patients with ischemic heart disease. Increased endothelin receptor activity may contribute to the smooth muscle cell proliferation, vasoconstriction and the decreased blood perfusion that is noted in atherosclerotic disease. The Ang II-induced vasoconstriction of endothelium-denuded human coronary arteries is caused by activation of angiotensin type 1 (AT1) and, to a lesser extent, angiotensin type 2 (AT2) receptors. AT1 receptor mRNA levels were decreased both in arteries from patients with ischemic heart disease and patients with heart failure due to other causes. In patients with heart failure, both the Ang II-induced contraction and the AT1 receptor mRNA levels diminished with increasing age, which may be due to a longer exposure to heart failure in older patients. Culture of human coronary arteries induced similar Ang II and endothelin receptor changes as in ischemic heart disease and heart failure. The Ang II induced contraction and the AT1 and AT2 receptor mRNA levels were decreased, while the ETB receptor mediated contraction and mRNA levels were increased. Organ culture may therefore provide an experimental method in which the development of Ang II and endothelin receptor changes on smooth muscle cells can be studied in detail to further delineate the mechanisms involved in receptor regulation during ischemic heart disease and heart failure.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Wallentén, Karin, et al.
(författare)
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Retinal function and PKC alpha expression after focal laser photocoagulation.
- 2007
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Ingår i: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 1435-702X .- 0721-832X. ; 245:12, s. 1815-1824
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To examine the effects of focal laser photocoagulation on general and local retinal function and to relate electrophysiological findings with changes in protein kinase C (PKC) alpha expression. METHODS: Twelve rabbits were treated with 70 spots of laser photocoagulation in the central cone-rich retina. The operated eyes were investigated with electroretinography (full-field ERG and multifocal electroretinography, mfERG) preoperatively and at 1, 3, and 5 weeks after surgery. The expression of PKC alpha was examined at all three time points using immunohistochemistry, and PKC alpha mRNA levels were quantified using real-time polymerase chain reaction (PCR). Immunohistochemistry for glial fibrillary acidic protein (GFAP) and hematoxylin and eosin staining was employed to monitor the extent and dynamics of the morphological response. RESULTS: The full-field ERG revealed a significant increase in b-wave amplitudes derived from the isolated rod response (blue light) at all three time points after surgery (p < 0.05). Supernormal b-wave amplitudes were also found for the combined rod-cone response at 3 weeks (white light), and for the isolated cone response (light-adapted 30-Hz flicker) at 5 weeks after treatment. In the mfERG, amplitudes derived from the central retina did not change postoperatively, while the implicit time was significantly increased at all time points. Immunohistochemistry for PKC alpha revealed a reduced expression of the enzyme in rod bipolar cells 1 and 3 weeks after laser treatment compared with untreated controls. Five weeks postoperatively, no PKC alpha labeling in rod bipolar cells was found in any part of the retina. Real-time PCR 1 and 3 weeks after treatment displayed a decreased level of PKC alpha mRNA compared to the controls. Immunolabeled tissue sections from laser-treated eyes displayed GFAP expression in Muller cells in the treated as well as untreated retina 1 week postoperatively. At 3 and 5 weeks, GFAP labeling was less pronounced and was concentrated around the laser-treated spots. CONCLUSIONS: Focal laser treatment in the rabbit eye induces local and wide-spread alterations in both rod- and cone-mediated retinal function in the form of supernormal b-wave amplitudes in the full-field ERG and increased latency in the mfERG. The electrophysiological abnormalities are accompanied by a progressive down-regulation of the PKC alpha isoenzyme in rod bipolar cells, reaching far beyond the treated area. PKC alpha is down-regulated directly by impaired protein synthesis, and also possibly indirectly by protein consumption related to GFAP up-regulation. The results indicate that focal laser photocoagulation interferes with PKC-alpha-mediated inhibitory regulation of inner retinal signal transmission.
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