MULTIPLE FACTORS CONTRIBUTE TO ACETYLCHOLINE-INDUCED RENAL AFFERENT ARTERIOLAR VASODILATION DURING MYOGENIC AND NOREPINEPHRINE-INDUCED AND KCL-INDUCED VASOCONSTRICTION - STUDIES IN THE ISOLATED-PERFUSED HYDRONEPHROTIC KIDNEY

Acetylcholine (ACh) elicits vasodilation by releasing a number of endo thelium-derived relaxing factors (EDRFs). We used the isolated perfuse d hydronephrotic rat kidney to examine the characteristics of ACh-indu ced vasodilation of renal afferent arterioles during different types o f underlying vasoconstriction. Basal arteriolar tone was increased by either elevating perfusion pressure to 180 mm Hg (myogenic), administe ring 0.3 mu mol/L norepinephrine (NE), or elevating medium potassium c oncentration to 30 mmol/L (KCl). ACh (10 mu mol/L) completely reversed myogenic and NE-induced vasoconstriction and reversed KCl-induced vas oconstriction by 80 +/- 5%. However, whereas ACh produced a sustained vasodilation during KCl- and NE-induced vasoconstriction, only a trans ient reversal of myogenic vasoconstriction was observed, and myogenic tone recovered within 5 to 10 minutes. ACh-induced vasodilation of art erioles preconstricted with KCl was markedly inhibited by either indom ethacin (100 mu mol/L) or nitro-L-arginine (100 mu mol/L) and was comp letely abolished by pretreatment with both inhibitors. In contrast, in domethacin and nitro-L-arginine had no effect on the transient respons e to ACh observed during pressure-induced vasoconstriction. In vessels preconstricted with NE, nitro-L-arginine converted the normally susta ined response to ACh to a transient vasodilation, which was refractory to both nitric oxide synthase and cyclooxygenase inhibition. Since th is component was not observed during KCl-induced vasoconstriction, it may reflect the actions of an, as yet unidentified, endothelium-derive d hyperpolarizing factor (EDHF). Our findings thus suggest that prosta noids, nitric oxide, and EDHF all contribute to ACh-induced renal affe rent arteriolar vasodilation and that the relative contributions of th ese individual EDRFs depends on the nature of the underlying renal vas cular tone.