Shear stress-induced dilation is attenuated in skeletal muscle arterioles of hypertensive rats.
Hypertension is thought to alter many of the functions of the vascular endothelium. The present study examines whether shear stress-induced endothelium-dependent skeletal muscle arteriolar dilation is compromised in genetically hypertensive rats. Changes in the diameter of isolated, perfused arterioles (approximately 60 microns) from gracilis muscles of 12-week-old normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR) were investigated. At a constant perfusion pressure (80 mm Hg), the active diameter of NWR and SHR arterioles was 57.1 +/- 2.0 and 50.9 +/- 3.5 microns, respectively (mean +/- SEM), while the passive diameter (in Ca(2+)-free solution) was 113.2 +/- 3.1 and 100.6 +/- 2.9 microns, respectively. Increases in wall shear stress (from 0 to 100 dyne/cm2) elicited by increases in perfusate flow (from 0 to 25 microL/min) resulted in marked increases in the diameter of NWR arterioles, but such increases produced substantially smaller dilations in SHR arterioles (43.0 versus 18.9 microns). The prostaglandin synthesis inhibitor indomethacin (10(-5) mol/L) significantly attenuated the shear stress-induced dilations in both strains of rats. In contrast, the nitric oxide synthase inhibitor N omega-nitro-L-arginine (10(-4) mol/L) significantly shifted the shear stress-diameter curve to the right in vessels from NWR (by 50 dyne/cm2) but not in those from SHR. Thus, in gracilis muscle arterioles of SHR, the reduced dilation to increases in shear stress seems to be due to the lack of nitric oxide synthesis and/or release in response to shear stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Koller
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Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
Huang
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000503:physiopathology; D001794:Blood Pressure; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D010477:Perfusion; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012016:Reference Values; D013314:Stress, Mechanical; D014664:Vasodilation / Q000187:drug effects
D011448:Prostaglandin Antagonists; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D007213:Indomethacin