Modulation of angiotensin II-induced vasoconstriction by endothelium-derived relaxing factor in the isolated microperfused rabbit afferent arteriole

Although endothelium-derived relaxing factor (EDRF) has been studied extensively in large vessels, little is known about its role in the preglomerular afferent arteriole (Af-Art). We tested the hypothesis that EDRF, which is produced locally in the Af-Art, modulates arteriolar responses to angiotensin II (All). A single rabbit Af-Art with its glomerulus intact was microperfused in vitro at 60 mmHg. When 0.1 μM AII was first applied, luminal diameter decreased by 49±7.0% (n = 9; P < 0.0001); however, constriction waned, with the decrease becoming 15±3.5% at 1 min. After washing the Af-Art, repeated AII caused less constriction (13±4.0%; P < 0.0002 vs. first application), showing tachyphylaxis. Pretreatment with N^w-nitro-L-arginine (N-Arg), which inhibits synthesis of nitric oxide (an EDRF), decreased basal diameter by 18±3.0% (n = 14; P < 0.0001). N-Arg also augmented All-induced constriction (86±6.8%; P < 0.02 vs. nontreated Af-Art) and rendered it persistent (82±6.9% at 1 min). Even after pretreatment with N-Arg, repeated All caused a weaker response, which was restored by washing with kidney homogenate rich in angiotensinase. In conclusion, this study provides evidence that local production of EDRF is an important determinant of the tone of the Af-Art. Our results suggest that the transient nature of All-induced constriction of the Af-Art may be due to production of EDRF, while tachyphylaxis may be the result of long lasting receptor occupancy.