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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Biological Factors, Endothelium, Vascular, Epoprostenol, Female, Guanylate Cyclase, Homeostasis, Male, Mesenteric Arteries, Mice, Mice, Inbred C57BL, Nitric Oxide, Nitric Oxide Donors, Pressure, Pyrazoles, Pyridines, Sex Characteristics, Spermine, Vasoconstriction.
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Do distinct endothelial pathways underlie sexual dimorphism in vascular auto-regulation? Context: Pre-menopausal females have a lower incidence of cardiovascular disease compared with age-matched males, implying differences in the mechanisms and pathways regulating vasoactivity. In small arteries, myogenic tone (constriction in response to raised intraluminal pressure) is a major determinant of vascular resistance. Endothelium-derived dilators, particularly NO, tonically moderate myogenic tone and, because the endothelium is an important target for female sex hormones, we investigated whether NO-mediated moderation of myogenic tone differed between the sexes. Pressure-diameter or relaxation concentration-response curves to the NO donor spermine-NO or soluble guanylate cyclase (sGC) stimulation (BAY41-2272) were constructed before and following drug intervention in murine mesenteric resistance arteries. Hypotensive responses to activators of the NO-sGC pathway were determined. Quantitative PCR and Western blotting were used for expression analysis. NO synthase inhibition enhanced myogenic tone of arteries of both sexes while block of endothelium-derived hyperpolarizing factor (EDHF) enhanced responses in arteries of females only. Spermine-NO concentration-dependently relaxed mesenteric arteries isolated from either sex. However, while inhibition of sGC activity attenuated responses of arteries from male mice only, endothelial denudation attenuated responses of arteries from females only. BAY41-2272 and spermine-NO-induced vasodilatation and hypotension were greater in males than in females.
assistant
NO moderated myogenic tone in arteries of male mice by a sGC-dependent pathway while EDHF was the predominant endothelial regulator in arteries of females. This is a potentially important sexual dimorphism in NO-mediated reactivity and further implicates EDHF as the predominant endothelial vasodilator in female resistance arteries. Final Decision: yes