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Arthritis and Rheumatism May 1993To determine the effects of local cooling on alpha-adrenergic responses in the fingers of patients with idiopathic Raynaud's disease.
OBJECTIVE
To determine the effects of local cooling on alpha-adrenergic responses in the fingers of patients with idiopathic Raynaud's disease.
METHODS
Clonidine HCl and phenylephrine HCl were administered through a brachial artery catheter while blood flow was measured by plethysmography in cooled and uncooled fingers.
RESULTS
Cooling potentiated alpha 2-adrenergic vasoconstriction in the patients but depressed this response in the controls. Vasoconstrictive responses to phenylephrine were not significantly affected by cooling but were significantly greater in the patients than in the controls.
CONCLUSION
Cold-induced sensitization of peripheral vascular alpha 2-adrenoceptors may be involved in the mechanism by which cooling triggers the vasospastic attacks of Raynaud's disease.
Topics: Adult; Clonidine; Cold Temperature; Dose-Response Relationship, Drug; Female; Fingers; Humans; Middle Aged; Phenylephrine; Raynaud Disease; Receptors, Adrenergic, alpha; Regional Blood Flow; Vasoconstriction
PubMed: 8387786
DOI: 10.1002/art.1780360517 -
Current Opinion in Rheumatology Nov 2005New insights in the pathophysiology and molecular mechanisms implicated in cutaneous vasomotor response to cooling are emerging from recent literature. These advances... (Review)
Review
PURPOSE OF REVIEW
New insights in the pathophysiology and molecular mechanisms implicated in cutaneous vasomotor response to cooling are emerging from recent literature. These advances are introducing significant changes in the management of Raynaud's phenomenon. In this review, we outline how these new findings are leading to novel methods of assessment and new opportunities for specific targeted therapy.
RECENT FINDINGS
New potential targets for treatment of Raynaud's phenomenon derive from experimental observations. Increased protein tyrosine kinase activity and tyrosine phosphorylation have been described in vascular smooth muscle cells in response to cooling and are linked to excessive alpha2-adrenergic response. Activation of Rho/Rho kinase pathway is triggered by increase of reactive oxygen species and up-regulates alpha2c-adrenergic receptors on the surface of vascular smooth muscle cells, thus determining an excessive vasoconstrictive response to cooling. This observation generated pilot trials testing rho-kinase inhibitors and alpha2c-adrenergic receptors antagonists in vasospastic conditions with encouraging results. Therapies already in use for pulmonary hypertension are also showing an effect in Raynaud's phenomenon. Studies evaluating anti-endothelin-1 (bosentan), phosphodiesterases inhibitors (sildenafil), and prostanoids (given for critical digital ischemia) in the treatment of Raynaud's phenomenon all determined improvement of symptoms and/or digital ischemic lesions. Novel techniques for better visualization and quantification of cutaneous microvascular defects are under development. The hope is that these new tools will allow earlier discrimination between primary and secondary Raynaud's phenomenon as well as a better way to predict outcome and response to therapy.
SUMMARY
Remarkable progress towards a rational approach to the management and treatment of Raynaud's phenomenon is emerging.
Topics: Adrenergic alpha-Antagonists; Humans; Phosphodiesterase Inhibitors; Prostaglandins; Raynaud Disease; Treatment Outcome; Vasoconstriction; Vasodilator Agents
PubMed: 16224254
DOI: 10.1097/01.bor.0000179944.35400.6e -
Clinical Pharmacology and Therapeutics May 1987Persistent vasospasm of the digits is difficult to attenuate or reverse. We studied the effect of intra-arterial nitroprusside on humoral and neurogenic digital... (Comparative Study)
Comparative Study
Persistent vasospasm of the digits is difficult to attenuate or reverse. We studied the effect of intra-arterial nitroprusside on humoral and neurogenic digital vasoconstriction. Fingertip blood flow (FBF) was measured by venous occlusion plethysmography and capillary flow (CF) by the disappearance rate of a local injection of radioisotope. Small doses of nitroprusside (1 to 2 micrograms/min) increased FBF in fingers vasoconstricted by intra-arterial norepinephrine (4.7 +/- SE 1.7 to 38.4 +/- 26 ml min-1 100 ml-1 of tissue). Large doses of nitroprusside (up to 40 micrograms/min) did not increase FBF (11.8 +/- 6.0 ml to 6.6 +/- 3.9 ml) in fingers vasoconstricted by sympathetic nerve stimulation (body cooling). Forearm blood flow was measured in six subjects in the cool room and all showed an increase in flow with nitroprusside (6.7 +/- 1.1 ml to 26.0 +/- 6.0 ml), demonstrating that effective doses were used. Nitroglycerin (2.5 to 5 micrograms/min) significantly increased FBF from 5.1 +/- 1.9 ml to 14.8 +/- 6.9 ml as did phentolamine (50 to 100 micrograms/min) from 6.7 +/- 2.8 ml to 36.0 +/- 11.3 ml in sympathetically vasoconstricted subjects. Only phentolamine increased CF significantly (0.8 +/- 0.2 ml to 2.8 +/- 0.6 ml). Nitroprusside is an effective vasodilator for humorally induced vasoconstriction, but sympathetic digital vasoconstriction is resistant to nitroprusside and nitroglycerin is less effective than phentolamine. Phentolamine is the preferred agent because it increased FBF and CF.
Topics: Female; Fingers; Humans; Injections, Intra-Arterial; Male; Nitroglycerin; Nitroprusside; Phentolamine; Vasoconstriction; Vasodilator Agents
PubMed: 3105944
DOI: 10.1038/clpt.1987.74 -
No Shinkei Geka. Neurological Surgery Feb 2014Reversible cerebral vasoconstriction syndrome(RCVS)is characterized by severe headache and diffuse segmental constriction of cerebral arteries that resolves...
Reversible cerebral vasoconstriction syndrome(RCVS)is characterized by severe headache and diffuse segmental constriction of cerebral arteries that resolves spontaneously within a few months. Although manifestations of stroke are not included in diagnostic criteria of RCVS, it is known that some cases may be associated with stroke, including intracerebral hemorrhage, subarachnoid hemorrhage, or cerebral infarction. We present three cases of RCVS associated with various types of stroke, and then review the literature. Case 1:A 49-year-old woman presented with a headache followed by left hemiparesis and dysarthria. One month before the onset, she was transfused for severe anemia caused by uterus myoma. CT images revealed intracerebral hemorrhages in the right putamen and right occipital lobe. Angiography revealed multiple segmental constrictions of the cerebral arteries. One month after the onset, these vasoconstrictions improved spontaneously. Case 2:A postpartum 38-year-old woman who had a history of migraine presented with thunderclap headache. Imaging revealed a focal subarachnoid hemorrhage in the right postcentral sulcus and segmental vasoconstriction of the right middle cerebral artery. One week after the onset, this vasoconstriction improved spontaneously. Case 3:A 32-year-old woman who had a history of migraine presented with headache followed by left homonymous hemianopsia. Imaging revealed a cerebral infarction of the right occipital lobe and multiple constrictions of the right posterior cerebral artery. These vasoconstrictions gradually improved spontaneously.
Topics: Adult; Cerebral Infarction; Female; Humans; Middle Aged; Stroke; Subarachnoid Hemorrhage; Vasoconstriction
PubMed: 24501186
DOI: No ID Found -
Pharmacological Research Jun 2004Vascular endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several vasodilating factors, such as prostacyclin, nitric... (Comparative Study)
Comparative Study Review
Vascular endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several vasodilating factors, such as prostacyclin, nitric oxide (NO), and a yet unidentified endothelium-derived hyperpolarizing factor (EDHF). Possible candidates for EDHF include epoxyeicosatrienoic acids (EETs), endothelium-derived potassium ions (K(+)), and as we have recently identified, hydrogen peroxide (H2O2). Electrical communication between endothelial and smooth muscle cells through gap junctions has also been suggested to be involved in endothelium-dependent hyperpolarization. Among the above candidates, the H2O2 hypothesis well explains the pathophysiological interactions between NO and EDHF and re-highlights the physiological roles of the reactive oxygen species (ROS) in endothelium-dependent vascular responses. This brief review summarizes our current knowledge about H2O2 as an EDHF, with special reference to its production by the endothelium, its action on membrane potentials and its pathophysiological roles.
Topics: Animals; Biological Factors; Dose-Response Relationship, Drug; Humans; Hydrogen Peroxide; Vasoconstriction; Vasodilation
PubMed: 15026032
DOI: 10.1016/j.phrs.2003.10.016 -
Pharmacology & Therapeutics 1993Endogenous cerebral vasoconstrictor mediators regulate vascular resistance and blood flow in the brain as a whole and in various regions and participate in the... (Review)
Review
Endogenous cerebral vasoconstrictor mediators regulate vascular resistance and blood flow in the brain as a whole and in various regions and participate in the pathogenesis of cerebral circulatory disturbances. Vasoconstrictors are effective in the treatment of diseases associated with cerebral vasodilatation. There are variations in the response of cerebral arteries from primate and subprimate mammals; therefore, information as to similarities and differences in their response is quite important in evaluating the physiological role, involvement in pathogenesis and therapeutic usefulness of the mediators in healthy men and patients. In this review we described characteristics of the action of vasoconstrictors (amines, peptides, prostanoids, and others) on isolated cerebral arteries from mammals, including humans and monkeys.
Topics: Animals; Cerebrovascular Circulation; Humans; Vasoconstriction; Vasoconstrictor Agents
PubMed: 8361998
DOI: 10.1016/0163-7258(93)90061-h -
British Journal of Pharmacology Aug 2014The α₁-adrenoceptor family plays a critical role in regulating ocular perfusion by mediating responses to catecholamines. The purpose of the present study was to...
BACKGROUND AND PURPOSE
The α₁-adrenoceptor family plays a critical role in regulating ocular perfusion by mediating responses to catecholamines. The purpose of the present study was to determine the contribution of individual α₁-adrenoceptor subtypes to adrenergic vasoconstriction of retinal arterioles using gene-targeted mice deficient in one of the three adrenoceptor subtypes (α₁A-AR(-/-), α₁B-AR(-/-) and α₁D-AR(-/-) respectively).
EXPERIMENTAL APPROACH
Using real-time PCR, mRNA expression for individual α₁-adrenoceptor subtypes was determined in murine retinal arterioles. To assess the functional relevance of the three α₁-adrenoceptor subtypes for mediating vascular responses, retinal vascular preparations from wild-type mice and mice deficient in individual α₁-adrenoceptor subtypes were studied in vitro using video microscopy.
KEY RESULTS
Retinal arterioles expressed mRNA for all three α₁-adrenoceptor subtypes. In functional studies, arterioles from wild-type mice with intact endothelium responded only negligibly to the α₁-adrenoceptor agonist phenylephrine. In endothelium-damaged arterioles from wild-type mice, phenylephrine evoked concentration-dependent constriction that was attenuated by the α₁-adrenoceptor blocker prazosin. Strikingly, phenylephrine only minimally constricted endothelium-damaged retinal arterioles from α₁B-AR(-/-) mice, whereas arterioles from α₁A -AR(-/-) and α₁D-AR(-/-) mice constricted similarly to arterioles from wild-type mice. Constriction to U46619 was similar in endothelium-damaged retinal arterioles from all four mouse genotypes.
CONCLUSIONS AND IMPLICATIONS
The present study is the first to demonstrate that α₁-adrenoceptor-mediated vasoconstriction in murine retinal arterioles is buffered by the endothelium. When the endothelium is damaged, a vasoconstricting role of the α₁B-adrenoceptor subtype is unveiled. Hence, the α₁B-adrenoceptor may represent a target to selectively modulate retinal blood flow in ocular diseases associated with endothelial dysfunction.
Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adrenergic alpha-1 Receptor Agonists; Animals; Arterioles; Endothelium, Vascular; Male; Mice, Inbred C57BL; Mice, Knockout; Phenylephrine; Receptors, Adrenergic, alpha-1; Retinal Vessels; Vasoconstriction; Vasoconstrictor Agents
PubMed: 24749494
DOI: 10.1111/bph.12743 -
Hypertension (Dallas, Tex. : 1979) Jul 2010Thiazolidinediones improve insulin resistance and endothelial dysfunction. However, the mechanisms underlying the vasoprotective effects of thiazolidinediones remain to... (Comparative Study)
Comparative Study
Thiazolidinediones improve insulin resistance and endothelial dysfunction. However, the mechanisms underlying the vasoprotective effects of thiazolidinediones remain to be fully elucidated. The present study aimed to examine the molecular mechanism for the anti-vasoconstrictive effects of rosiglitazone in response to endothelin (ET) 1. Mouse aortas were treated with rosiglitazone for 24 hours, and ET-1-induced vasoconstriction was assessed by wire myography. The results showed that rosiglitazone attenuated ET-1-induced contraction in mouse aortas; this effect was abolished by ET-B receptor (ET(B)R) antagonist, NO synthase inhibitor, and by the removal of endothelium. By using Northern blotting, real-time RT-PCR, Western blotting, and immunohistochemical techniques, we found that rosiglitazone upregulated expression of ET(B)R at both mRNA and protein levels in mouse aortas and human vascular endothelial cells. The induction of ET(B)R was prevented by peroxisome proliferator-activated receptor-gamma antagonism. Luciferase reporter assay showed that rosiglitazone enhanced ET(B)R gene promoter activity. Furthermore, chromatin immunoprecipitation assays demonstrated that peroxisome proliferator-activated receptor-gamma can directly bind to ET(B)R gene promoter. Furthermore, in vivo treatment with rosiglitazone also attenuated the ET-1-induced vasoconstrictions and increased the ET(B)R expression in mouse aortas and mesenteric arteries. In conclusion, these results demonstrate that rosiglitazone attenuated ET-1-induced vasoconstriction through the upregulation of endothelial ET(B)R, which is a peroxisome proliferator-activated receptor-gamma direct target.
Topics: Animals; Blotting, Northern; Blotting, Western; Cells, Cultured; Chromatin Immunoprecipitation; Disease Models, Animal; Endothelin-1; Endothelium, Vascular; Gene Expression Regulation; Humans; Hypoglycemic Agents; Immunohistochemistry; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; RNA; Receptor, Endothelin B; Reverse Transcriptase Polymerase Chain Reaction; Rosiglitazone; Thiazolidinediones; Vasoconstriction; Vasodilator Agents
PubMed: 20516393
DOI: 10.1161/HYPERTENSIONAHA.110.150375 -
Circulation Oct 1995Coronary vasoconstriction has been described after uncomplicated percutaneous transluminal coronary angioplasty (PTCA). However, it is still unknown whether this...
BACKGROUND
Coronary vasoconstriction has been described after uncomplicated percutaneous transluminal coronary angioplasty (PTCA). However, it is still unknown whether this phenomenon is limited to coronary circulation. The present study was planned to assess the effects of a successful PTCA on forearm blood flow (FBF) and resistance. The role of alpha-adrenoceptors and calcium antagonist agents on PTCA-induced limb blood flow changes was also investigated.
METHODS AND RESULTS
We prospectively studied 37 patients scheduled for elective single PTCA of the left anterior descending coronary artery. All patients had evidence of exercise-induced myocardial ischemia. All vasoactive drugs were withdrawn for at least 48 hours before the study. FBF was measured by calibrated venous occlusion plethysmography. A significant reduction of FBF was observed at 1, 5, and 15 minutes after PTCA (from 3.7 +/- 1.2 to 2.7 +/- 1.5, 3.0 +/- 1.6, and 2.9 +/- 1.9 mL/100 mL tissue per minute, respectively; all P < .05 versus baseline). Vascular forearm resistance also increased at 1, 5, and 15 minutes after PTCA (from 27 +/- 8 to 42 +/- 16, 37 +/- 10, and 43 +/- 19 U, respectively; all P < .05 versus baseline). Phentolamine (12 microgram.kg-1.min-1, n = 7) or verapamil (3.5 micrograms.kg-1.min-1, n = 7) also was infused intra-arterially. PTCA-induced forearm vasoconstriction was completely abolished by pretreatment with regional infusion of phentolamine or verapamil.
CONCLUSIONS
After an uncomplicated PTCA of the left anterior descending coronary artery, a reduction in FBF and an increase in forearm vascular resistance were observed. This peripheral vasoconstrictive response was probably due to alpha-adrenergic stimulation and was abolished by intra-arterial infusion of calcium antagonist agents.
Topics: Adrenergic alpha-Antagonists; Angioplasty, Balloon, Coronary; Calcium Channel Blockers; Circadian Rhythm; Coronary Disease; Female; Forearm; Humans; Male; Middle Aged; Phentolamine; Plethysmography; Premedication; Prospective Studies; Regional Blood Flow; Time Factors; Vascular Resistance; Vasoconstriction; Verapamil
PubMed: 7554189
DOI: 10.1161/01.cir.92.8.2109 -
Biological Research For Nursing Apr 2004Male sex is an acknowledged risk factor for many forms of cardiovascular disease, and vascular disease prevalence patterns appear to be different in men versus women.... (Review)
Review
Male sex is an acknowledged risk factor for many forms of cardiovascular disease, and vascular disease prevalence patterns appear to be different in men versus women. The vascular properties of the principal mammalian androgen, testosterone, are complex and linked to dose, duration of exposure, presence of underlying vascular disease, and, possibly, biological sex. Data from isolated vessels and animal models suggest that pharmacological doses of testosterone, or its potent intracellular metabolite dihydrotestosterone, produce vasodilation. Testosterone's major effect on vascular beds at physiologic concentrations remains unclear, with documentation of both vasodilatory and vasoconstrictive actions. Results of various studies suggest that testosterone can alter vascular tone through both endothelium-dependent and endothelium-independent mechanisms in a variety of vascular beds and vessel types. Testosterone's endothelium-dependent effects are likely mediated at least in part through nitric oxide (NO) elaboration, whereas mechanisms of endothelium-independent effects involve 1 or more types of smooth muscle ion conductance channels. Data from clinical studies indicate that, in men, androgen replacement may provide beneficial effects when coronary artery disease is present. Conversely, in women, testosterone may augment existing hypertension, increase risk for cardiovascular events, or promote atherogenesis. However, it should be emphasized that most of these observations are anecdotal or come from small-scale clinical studies, and limited information is available in women. New research is required to understand the potential efficacy of androgen therapy, or lack thereof. This review focuses on current understanding of testosterone's physiological effects on vascular behavior and of testosterone's putative role in vascular health and disease.
Topics: Adult; Animals; Cardiovascular Diseases; Endothelium, Vascular; Female; Humans; Male; Sex Factors; Testosterone; Vasoconstriction; Vasodilation
PubMed: 15068657
DOI: 10.1177/1099800403262927