| 1. |
- Bondesson, Susanne, et al.
(författare)
-
Comparison of patients undergoing enhanced external counterpulsation and spinal cord stimulation for refractory angina pectoris.
- 2008
-
Ingår i: Coronary Artery Disease. - 0954-6928. ; 19:8, s. 627-634
-
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.
|
|
| 2. |
- Bondesson, Susanne, et al.
(författare)
-
Effects on blood pressure in patients with refractory angina pectoris after enhanced external counterpulsation
- 2010
-
Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 19:5, s. 287-294
-
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.
|
|
| 3. |
- Edvinsson, Lars, et al.
(författare)
-
Triptan-induced contractile (5-HT1B receptor) responses in human cerebral and coronary arteries: relationship to clinical effect
- 2005
-
Ingår i: Clinical Science. - 1470-8736. ; 109:3, s. 335-342
-
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.
|
|
| 4. |
- Johnsson, Evelina, et al.
(författare)
-
Enhanced expression of contractile endothelin ET(B) receptors in rat coronary artery after organ culture.
- 2008
-
Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 582:1-3, s. 94-101
-
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.
|
|
| 5. |
- Nilsson, David, et al.
(författare)
-
Endothelin receptor-mediated vasodilatation: Effects of organ culture.
- 2008
-
Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 579:1-3, s. 233-240
-
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.
|
|
| 6. |
- Nilsson, David, et al.
(författare)
-
Increased ET(A) and ET(B) receptor contraction in the left internal mammary artery from patients with hypertension.
- 2008
-
Ingår i: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 1476-5527 .- 0950-9240. ; 22:3, s. 226-229
-
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.
|
|
| 7. |
- Nilsson, David, et al.
(författare)
-
PKC and MAPK signalling pathways regulate vascular endothelin receptor expression
- 2008
-
Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 580:1-2, s. 190-200
-
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.
|
|
| 8. |
- Nilsson, David, et al.
(författare)
-
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
-
Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 8
-
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.
|
|
| 9. |
|
|
| 10. |
- Wackenfors, Angelica, et al.
(författare)
-
Angiotensin II-induced vasodilatation in cerebral arteries is mediated by endothelium-derived hyperpolarising factor.
- 2006
-
Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 531:1-3, s. 259-263
-
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.
|
|
