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Impaired Response to Acetylcholine Despite Intact Endothelium-Derived Relaxing Factor/Nitric Oxide in Isolated Microperfused Afferent Arterioles of the Spontaneously Hypertensive Rat

Ito Sadayoshi; Carretero, Oscar A.
Journal of Cardiovascular Pharmacology: April 1992
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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 Nω-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).

Address correspondence and reprint requests to Dr. S. Ito at Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, U.S.A.

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