Corelease of nitric oxide and prostaglandins mediates flow-dependent dilation of rat gracilis muscle arterioles.
We have studied the mechanisms responsible for the mediation of flow (shear stress)-induced dilation of isolated arterioles of rat gracilis muscle. Active diameter of arterioles at a constant perfusion pressure (PP, 80 mmHg) was approximately 92 microns, while their passive diameter (Ca(2+)-free solution) was approximately 165 microns. At a constant PP the stepwise increase in flow of the perfusion solution (PS, 0-60 microliters/min in 10-microliters/min steps) elicited a gradual increase in diameter up to approximately 140 microns. Flow-induced dilations were eliminated by the removal of the endothelium of arterioles (by air). Dilations were significantly reduced by the cyclooxygenase blocker, indomethacin (Indo, 10(-5) M), by the nitric oxide synthase blocker, N omega-nitro-L-arginine (L-NNA, 10(-4) M), or by the endothelium-derived relaxing factor inhibitor, oxyhemoglobin (Hb, 10(-5) M), as indicated by the significant changes in the slope of the regression lines of the flow-diameter curves. For example, during administration of the inhibitors, dilation to 60 microliters/min perfusate flow was reduced by 41.1, 54.3, and 39.3%, respectively. Combined application of Indo and L-NNA almost completely eliminated flow-induced dilation. Arteriolar dilation maintained calculated wall shear stress close to control values (approximately 30 dyn/cm2 at 60 microliters/min) despite increases in flow, but when the dilation was inhibited by removal of the endothelium or by the combined administration of Indo and L-NNA, wall shear stress was greatly increased as a function of increases in flow of the PS (approximately 125 dyn/cm2).(ABSTRACT TRUNCATED AT 250 WORDS)
Koller
A
A
Department of Physiology, New York Medical College, Valhalla 10595.
Sun
D
D
Huang
A
A
Kaley
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006614:Hindlimb; D008297:Male; D009132:Muscles / Q000098:blood supply*; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D014664:Vasodilation / Q000502:physiology*
D011453:Prostaglandins; D009599:Nitroprusside; D009569:Nitric Oxide; D000109:Acetylcholine