Impaired response to acetylcholine despite intact endothelium-derived relaxing factor/nitric oxide in isolated microperfused afferent arterioles of the spontaneously hypertensive rat.
The major characteristic of renal hemodynamics in hypertension is abnormally high resistance of the preglomerular vessel, most likely the afferent arteriole (Af-Art). Although endothelium-derived relaxing factor (EDRF)/nitric oxide (NO) has been studied extensively in large vessels, little is known about its role in Af-Art reactivity. Using isolated microperfused Af-Arts of 12- to 13-week-old spontaneously hypertensive rats (SHRs) and their normotensive control, Wistar-Kyoto (WKY) rats, we examined the effect of acetylcholine (ACh) or N omega-nitro-L-arginine (L-NAME), which stimulates or blocks endothelium-derived NO, respectively. Af-Arts were preconstricted with norepinephrine to 70 +/- 5 and 62 +/- 4% of the control diameter in SHRs and WKY rats, respectively; the intraluminal pressure was kept at either 100 or 70 mm Hg. In SHRs, ACh (1 nM-0.1 mM) added to the Af-Art perfusate caused no vasodilation but tended to decrease the diameter further to 59 +/- 6% of control (N = 8). In contrast, in WKY rats, ACh reversed the luminal diameter to 90 +/- 4% of control (N = 6, p < 0.01 compared with SHRs). Contrary to the responses to ACh, blockade of endothelium-derived NO with L-NAME decreased the basal diameter by 31 +/- 8 and 14 +/- 5% in SHRs and WKY rats, respectively. We conclude that ACh-induced vasodilation is impaired in SHR Af-Art. The impaired response to ACh may be due to factors other than endothelium-derived NO such as endothelium-derived contracting factor (EDCF).
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine