| 21. |
- Edvinsson, MarieLouise, et al.
(författare)
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Brain natriuretic peptide is a potent vasodilator in aged human microcirculation and shows a blunted response in heart failure patients.
- 2014
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Ingår i: Journal of geriatric cardiology : JGC. - 1671-5411. ; 11:1, s. 50-56
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Tidskriftsartikel (refereegranskat)abstract
- Brain natriuretic peptide (BNP) is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects (CHF). BNP has natriuretic effects and is a potent vasodilator. It is suggested that BNP could be a therapeutic alternative in CHF. However, we postulated that the high levels of circulating BNP in CHF may downregulate the response of microvascular natriuretic receptors. This was tested by comparing 15 CHF patients (BNP > 3000 ng/L) with 10 matched, healthy controls.
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| 22. |
- Edvinsson, MarieLouise, et al.
(författare)
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Cigarette smoking leads to reduced relaxant responses of the cutaneous microcirculation.
- 2008
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Ingår i: Vascular Health and Risk Management. - 1178-2048. ; 4:3, s. 699-704
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Smoking is a major risk factor for cardiovascular disease. The present study was undertaken to examine if cigarette smoking translates into reduced relaxant responses of the peripheral microcirculation. METHODS: The cutaneous forearm blood flow was measured by laser Doppler flowmetry. The vasodilator response to the iontophorectic administration of acetylcholine (ACh), acting via an endothelial mechanism, and sodium nitroprusside (SNP), and acting via a smooth muscle mechanism were studied. The study population consisted of 17 nonsmokers and 17 current smokers (mean age 64+/-2 years, 13 females and 4 males) in each matched group. RESULTS: There was no difference between the groups in baseline characteristics or in basal flow. Smokers showed however significantly reduced responses to both ACh (mean +/- SEM, from 973+/-137% in nonsmokers to 651+/-114% in smokers, p<0.05) and SNP (from 575+/-111% in nonsmokers to 355+/-83% in smokers, p<0.05). The response to the local heating (44 degrees C) was reduced in smokers (from 1188+/-215% in nonsmokers to 714+/-107% in smokers, p<0.01). In addition, there was no difference between men and women within the groups. CONCLUSIONS: The data show that cigarette smoking results in reduced peripheral microvascular responses to both endothelial and smooth muscle cell stimulation in healthy subjects, suggesting a generalized microvascular vasomotor function.
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| 23. |
- Edvinsson, Marie-Louise, et al.
(författare)
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Characterization of Relaxant Responses to Natriuretic Peptides in the Human Microcirculation In Vitro and In Vivo
- 2016
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Ingår i: Microcirculation. - : Wiley. - 1073-9688. ; 23:6, s. 438-446
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We characterized the vasodilatory effects of ANP, BNP, and CNP in human subcutaneous arterioles in vitro and the cutaneous microcirculation in vivo. Methods: The in vitro experiments were performed using wire myography and the responses were characterized by the use of inhibitors for nitric oxide (L-NAME), prostaglandin synthesis (indomethacin), or the endothelium-derived hyperpolarization factor. In vivo, the vasorelaxant effect of iontophoretically administrated BNP or CNP was measured with a noninvasive laser Doppler technique. Involvement of nitric oxide or prostaglandins was assessed by L-NAME or indomethacin given by iontophoresis. Results: In vitro all three peptides showed significant vasodilatation with the efficacy order: CNP > BNP = ANP. The BNP-induced vasodilatation, but not that of ANP or CNP, was significantly reduced by pretreatment with indomethacin or L-NAME. In vivo administration of BNP induced a marked vasodilatory response that was attenuated by local pretreatment of L-NAME. Indomethacin by itself resulted in increased cutaneous perfusion. Conclusions: NPs are potent vasodilators in the human subcutaneous circulation. The response to BNP differs from that of the other peptides as it seems dependent on cyclooxygenase products and nitric oxide.
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| 24. |
- Edvinsson, M-L, et al.
(författare)
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Comparison of CGRP and NO responses in the human peripheral microcirculation of migraine and control subjects.
- 2008
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 28:5, s. 563-566
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Tidskriftsartikel (refereegranskat)abstract
- Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are two molecules shown to have a role in migraine pathophysiology. Our objective was to test the hypothesis that migraine subjects are particularly sensitive to these signal molecules. The cutaneous microvascular responses to endothelial and non-endothelial dependent dilators were tested using laser Doppler flowmetry in combination with iontophoresis. The blood flow responses to iontophoretic administration of the endothelium-dependent vasodilator acetylcholine (ACh), or to the endothelium-independent dilators sodium nitroprusside (SNP) and CGRP, and to local warming (44 degrees C) were compared in this controlled trial. The design was that of two arms: patients diagnosed with migraine without aura (n = 9) for >10 years were compared with nine healthy subjects matched for age and gender (seven female and two male, age range 30-60 years). Iontophoretic administration resulted in local vasodilation. ACh induced a relaxation of 1225 +/- 245% (relative to baseline) in controls and 1468 +/- 368% (P > 0.05) in migraine. The responses to SNP were 873 +/- 193% in controls and 1080 +/- 102% (P > 0.05) in migraine subjects. The responses to CGRP were 565 +/- 89% in controls and 746 +/- 675% (P > 0.05) in migraine patients. The responses to local heating which induced maximum dilation did not differ between the groups (1976 +/- 314% for controls and 1432 +/- 226% in migraine; P > 0.05. We conclude that there is no change in the microvascular responsiveness of the subcutaneous microvasculature in migraine.
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| 25. |
- Kruuse, Christina, et al.
(författare)
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Differential vasoactive effects of sildenafil and tadalafil on cerebral arteries
- 2012
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 674:2-3, s. 345-351
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Tidskriftsartikel (refereegranskat)abstract
- Phosphodiesterase 5 (PDE5) is associated with migraine pathophysiology, stroke recovery and vasospasm treatment The potential vascular interplay of PDE5 inhibitors sildenafil, tadalafil and UK-114,542 was studied by intra- versus extra-luminal administration in rat middle cerebral arteries in vitro and on middle meningeal arteries in vivo. By Western blot PDE5 was detected in both cerebral and meningeal arteries, though with minor variations in band intensity between vascular beds. Rat middle cerebral artery diameter was investigated using pressurised arteriography, applying UK-114,542, sildenafil, and tadalafil intra- or extraluminally. Effects on the dural middle meningeal artery were studied in the in vivo closed cranial window model. At high concentrations, abluminal sildenafil and UK-114,542, but not tadalafil, induced dilatation of the middle cerebral artery. Luminal application elicited a contraction of 4% (sildenafil, P = 0.03) and 10% (tadalafil, P = 0.02). In vivo, sildenafil, but not tadalafil, dose-dependently dilated middle meningeal artery concomitant to blood pressure reduction (1-3 mg/kg);1 mg/kg sildenafil inducing 60 +/- 14% (P = 0.04) and vehicle (DMSO) 13 +/- 6% dilatation. In conclusion, PDE5 inhibitors applied luminally had minor contractile effect, whereas abluminal sildenafil induced middle cerebral artery dilatation above therapeutic levels. In vivo, sildenafil dilated middle meningeal artery concomitant with a reduction in blood pressure. Tadalafil had no dilatory effects. PDE5 inhibitors show differential vascular activity in cerebral arteries from healthy animals; arterial dilatation is seen primarily above therapeutic levels. Such findings support clinical studies showing no vasodilator effects of sildenafil on cerebral arteries in healthy subjects. (C) 2011 Elsevier B.V. All rights reserved.
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| 26. |
- Lindstedt, Isak H., et al.
(författare)
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Reduced responsiveness of cutaneous microcirculation in essential hypertension - A pilot study
- 2006
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 15:5, s. 275-280
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Our hypothesis states that the reactivity of the cutaneous microcirculation is reduced in patients with hypertension compared with healthy subjects. The objective was to verify the hypothesis by measuring microvascular function in hypertensive patients. Design. The study was a controlled trial with two arms: 15 hypertensives and 15 normotensives were enrolled, aged 30-60 years, and in hypertensives, a diastolic blood pressure of > 90 mmHg. The hypertensive patients were compared with gender- and age-matched controls having a diastolic blood pressure < 90 mmHg. The patients were kept on their medication. Method. The local cutaneous forearm blood flow was measured by Laser-Doppler flowmetry. The blood flow response to local warming (44 degrees C), to the endothelium-dependent vasodilator acetylcholine (ACh), or to the endothelium-independent dilators sodium nitroprusside (SNP) and calcitonin gene-related peptide (CGRP) administered by iontophoresis were determined. Inflammatory markers and NT-pro brain natriuretic peptide (NT-proBNP) levels in plasma was also measured. Electrocardiograms (ECG) were evaluated and the subjects answered a lifestyle questionnaire. Results. The percentage change in vasodilator response to CGRP was significantly lower in the hypertensives compared with normotensives, 285% (95% CI 86-484) vs 764% (95% CI 366-1162) of baseline, p < 0.05. The change to local warming was 2191% (95% CI 1574-2807) in normotensives vs 1384% (95% CI 852-1917) in the hypertensives, p < 0.05. The vasodilator response to ACh was 1249% (95% CI 895-1602) in the normotensives and 873% (95% CI 610-1136) in the hypertensives. The vasodilator response to SNP in the normotensives was 771% (95% CI 436-1107) and 682% (95% Cl 416-948) in the hypertensive group. Plasma level of NT-proBNP was 90 ng/l (95% CI 35-145) in normotensives vs 285 ng/l (95% CI 70-499) in hypertensives (p=0.06). The ECGs showed a tendency towards left ventricular hypertrophy (LVH) in hypertensives. Conclusion. Patients with essential hypertension had significantly reduced microvascular dilator responses to CGRP and to local warming. Also, there was a tendency towards reduced responses to ACh. This points towards a generally weaker responsiveness of the cutaneous microvessels in hypertensives and could be a contributing factor to the development of high blood pressure. Patients with essential hypertension also had a tendency of higher plasma levels of NT-proBNP, which could be seen as an early sign of organ damage.
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| 27. |
- Maddahi, Aida, et al.
(författare)
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Progesterone distribution in the trigeminal system and its role to modulate sensory neurotransmission : influence of sex
- 2023
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Ingår i: Journal of Headache and Pain. - 1129-2369. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women are disproportionately affected by migraine, representing up to 75% of all migraine cases. This discrepancy has been proposed to be influenced by differences in hormone levels between the sexes. One such hormone is progesterone. Calcitonin gene-related peptide (CGRP) system is an important factor in migraine pathophysiology and could be influenced by circulating hormones. The purpose of this study was to investigate the distribution of progesterone and its receptor (PR) in the trigeminovascular system, and to examine the role of progesterone to modulate sensory neurotransmission. Methods: Trigeminal ganglion (TG), hypothalamus, dura mater, and the basilar artery from male and female rats were carefully dissected. Expression of progesterone and PR proteins, and mRNA levels from TG and hypothalamus were analyzed by immunohistochemistry and real-time quantitative PCR. CGRP release from TG and dura mater were measured using an enzyme-linked immunosorbent assay. In addition, the vasomotor effect of progesterone on male and female basilar artery segments was investigated with myography. Results: Progesterone and progesterone receptor -A (PR-A) immunoreactivity were found in TG. Progesterone was located predominantly in cell membranes and in Aδ-fibers, and PR-A was found in neuronal cytoplasm and nucleus, and in satellite glial cells. The number of positive progesterone immunoreactive cells in the TG was higher in female compared to male rats. The PR mRNA was expressed in both hypothalamus and TG; however, the PR expression level was significantly higher in the hypothalamus. Progesterone did not induce a significant change neither in basal level nor upon stimulated release of CGRP from dura mater or TG in male or female rats when compared to the vehicle control. However, pre-treated with 10 µM progesterone weakly enhanced capsaicin induced CGRP release observed in the dura mater of male rats. Similarly, in male basilar arteries, progesterone significantly amplified the dilation in response to capsaicin. Conclusions: In conclusion, these results highlight the potential for progesterone to modulate sensory neurotransmission and vascular responses in a complex manner, with effects varying by sex, tissue type, and the nature of the stimulus. Further investigations are needed to elucidate the underlying mechanisms and physiological implications of these findings.
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| 28. |
- Maddahi, Aida, et al.
(författare)
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The role of tumor necrosis factor-alpha and TNF-alpha receptors in cerebral arteries following cerebral ischemia in rat
- 2011
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tumour necrosis factor-alpha (TNF-alpha) is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-alpha acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the cell surface. The aim of this study was first to investigate if there is altered expression of TNF-alpha and TNF-alpha receptors in cerebral artery walls following global or focal ischemia, and after organ culture. Secondly, we asked if the expression was regulated via activation of the MEK-ERK1/2 pathway. Methods: The hypothesis was tested in vivo after subarachnoid hemorrhage (SAH) and middle cerebral artery occlusion (MCAO), and in vitro by organ culture of isolated cerebral arteries. The localization and amount of TNF-alpha, TNF-alpha receptor 1 and 2 proteins were analysed by immunohistochemistry and western blot after 24 and 48 h of organ culture and at 48 h following SAH or MCAO. In addition, cerebral arteries were incubated for 24 or 48 h in the absence or presence of a B-Raf inhibitor (SB386023-b), a MEK-inhibitor (U0126) or an NF-kappa B inhibitor (IMD-0354), and protein expression evaluated. Results: Immunohistochemistry revealed enhanced expression of TNF-alpha, TNF-R1 and TNF-R2 in the walls of cerebral arteries at 48 h after MCAO and SAH compared with control. Co-localization studies showed that TNF-alpha, TNF-R1 and TNF-R2 were primarily localized to the cell membrane and the cytoplasm of the smooth muscle cells (SMC). There was, in addition, some expression of TNF-R2 in the endothelial cells. Immunohistochemistry and western blot analysis showed that these proteins were upregulated after 24 and 48 h in culture, and this upregulation reached an apparent maximum at 48 h of organ culture. Treatment with U0126 significantly reduced the enhanced SMC expression of TNF-a alpha, TNF-R1 and TNF-R2 immunoreactivities after 24 and 48 h of organ culture. The Raf and NF-kappa B inhibitors significantly reduced organ culture induced TNF-alpha expression while they had minor effects on the TNF-alpha receptors. Conclusion: The present study shows that cerebral ischemia and organ culture induce expression of TNF-alpha and its receptors in the walls of cerebral arteries and that upregulation is transcriptionally regulated via the MEK/ERK pathway.
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| 29. |
- Minthon, Lennart, et al.
(författare)
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Correlation between clinical characteristics and cerebrospinal fluid neuropeptide Y levels in dementia of the Alzheimer type and frontotemporal dementia
- 1996
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Ingår i: Alzheimer Disease and Associated Disorders. - 1546-4156. ; 10:4, s. 197-203
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y (NPY) has been shown to be involved in the control of several neuroendocrine functions. Moreover, in animal models, NPY produces behavioral effects that are similar to those induced by anxiolytics. We studied NPY-like immunoreactivity (NPY-LI) in cerebrospinal fluid (CSF) in two primary degenerative dementias, Alzheimer disease (AD, n = 34) and frontotemporal dementia (FTD, n = 22) and correlated the CSF NPY-LI levels with clinical characteristics, as rated with the Organic Brain Syndrome scale. There were significant correlations between NPY-LI and such clinical items as suspiciousness, anxiousness, restlessness-agitation, and irritability in both AD and FTD. AD patients, but not FTD patients, showed a significant negative correlation between NPY-LI and duration of the disease. Thus, the study found significant correlations between CSF NPY-LI and emotional symptoms and behavior in organic dementia.
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| 30. |
- Minthon, Lennart, et al.
(författare)
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Long-term effects of tacrine on regional cerebral blood flow changes in Alzheimer's disease
- 1995
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Ingår i: Dementia and Geriatric Cognitive Disorders. - 1420-8008. ; 6:5, s. 245-251
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Tidskriftsartikel (refereegranskat)abstract
- Regional cerebral blood flow (rCBF) was studied in patients with Alzheimer's disease (AD) before and after 14 months of tacrine treatment. The treated group was compared with an identical reference group of untreated AD patients. At baseline the two groups showed an identical rCBF and mean hemispheric blood flow. After 14 months the tacrine-treated patients showed a stable rCBF level and a significant increase in rCBF in the central-parietal regions, compared to the untreated reference group, who showed typical AD reductions in rCBF in these regions. Clinical outcome: 7 of 9 patients in the tacrine group were clinically unchanged or slightly improved during the study time. In the untreated group 8 of 11 patients had deteriorated in clinical assessments and none had improved. Long-term tacrine treatment in Alzheimer's disease may delay the progression of symptoms.
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