Impaired nitric oxide-mediated flow-induced dilation in arterioles of spontaneously hypertensive rats.
We tested the hypothesis that impairment of flow-dependent dilator mechanisms of skeletal muscle arterioles is one of the underlying reasons for the increased peripheral resistance in hypertension. Isolated, cannulated arterioles (approximately 55 microns) of gracilis muscle of 12-week-old spontaneously hypertensive (SH) and normotensive Wistar (NW) rats were investigated. At a constant perfusion pressure (80 mm Hg), the active diameters of NW and SH arterioles were 57.7 +/- 1.9 and 51.5 +/- 3.2 microns, whereas their passive diameters (Ca(2+)-free solution) were 113.6 +/- 2.9 and 101.7 +/- 2.9 microns, respectively. Flow-induced dilation was elicited by increases in flow of the perfusion solution from 0 to 25 microL/min in 5-microL/min steps. This response was significantly less in arterioles of SH compared with NW rats. For example, at 25-microL/min flow, the diameter of arterioles of SH rats was approximately 56% less (P < .05) than those of NW rats. Indomethacin, an inhibitor of prostaglandin synthesis, significantly attenuated the flow-diameter curve in both strains of rats. In contrast, N omega-nitro-L-arginine, a nitric oxide synthase inhibitor, significantly shifted the flow-diameter curve to the right in NW rats, but it did not affect the flow-diameter curve in SH rats. Thus, the present findings demonstrate that in gracilis muscle arterioles of normotensive rats in response to increases in flow (shear stress), prostaglandins and nitric oxide are co-released, resulting in a dilation. In early hypertension, however, there is a reduced arteriolar dilation to increases in flow that is due to the impairment of the nitric oxide-mediated portion of the flow-dependent arteriolar dilation.
Koller
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Department of Physiology, New York Medical College, Valhalla 10595.
Huang
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000098:blood supply*; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D011453:Prostaglandins; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D007213:Indomethacin