Mediator role of prostaglandins in acetylcholine-induced vasodilation and control of resting vascular diameter in the hamster cremaster microcirculation in vivo.
Acetylcholine (ACh) is widely used as a standard test substance for nitric oxide (NO)-mediated vasodilation. However, it also augments the release of prostaglandins, a group of other endothelium-derived smooth muscle relaxants. Using intravital microscopy in the cremaster muscle of anesthetized hamsters, we studied the relative roles of NO and prostaglandins in mediating ACh-induced dilation and in the control of basal vessel tone (253 arterioles in 31 experiments) N omega-nitro-L-arginine (L-NNA), a competitive inhibitor of NO synthase, significantly reduced ACh-induced vasodilation (by 42-73%), irrespective of whether it was applied intravenously (30 mg/kg) or topically (30 microM). Additional indomethacin (3 microM, topical) nearly abolished the dilator response. In contrast, the vascular responses to the endothelium-independent dilator sodium nitroprusside were not affected. The resting diameters (range: 6-114 microns) were significantly (p < 0.05) reduced after L-NNA or indomethacin by 10.2 and 16.6% of control diameter, respectively. The constriction induced by L-NNA was stronger in larger (> 50 microns) than in smaller (< 50 microns) vessels, whereas indomethacin was equipotent in both groups. Thus, in addition to NO, dilating prostaglandins are important mediators of the ACh-induced dilation and contribute to the control of resting arteriolar diameter in the hamster cremaster microcirculation in vivo.
Institute of Physiology, Medical University of Lübeck, FRG.
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C
de Wit
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von Bismarck
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U
Pohl
D000009:Abdominal Muscles / Q000098:blood supply*; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006224:Cricetinae; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D012146:Rest; D014664:Vasodilation / Q000502:physiology*
D011453:Prostaglandins; D009599:Nitroprusside; D019335:Nitroarginine; D001120:Arginine; D000109:Acetylcholine; D007213:Indomethacin