Distinct role of nitric oxide and endothelium-derived hyperpolarizing factor in renal microcirculation. Studies in the isolated perfused hydronephrotic kidney.

BACKGROUND Both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) are established as important factors determining the vascular tone. The relative contribution of these factors to the renal microvascular tone, however, has not been delineated. METHODS Isolated perfused hydronephrotic rat kidneys were used to characterize the relative role of NO and EDHF in mediating the tone of interlobular arteries (ILA) and afferent arterioles (AFF). RESULTS During the norepinephrine constriction, acetylcholine (ACH, 1 micromol/l) induced a sustained vasodilation of ILA (90 +/- 9% reversal) and AFF (117 +/- 13% reversal). In the presence of nitro-L-arginine methylester (LNAME), the ACH-induced vasodilation of ILA and AFF was converted to transient dilation, with only 53 +/- 7 and 32 +/- 7% reversal observed 10 min after 1 micromol/l ACH (i.e sustained phase). In contrast, LNAME had no effect on the initial phase of ACH-induced dilation. In the presence of apamin + charybdotoxin, the initial vasodilator response to ACH (1 micromol/l) was diminished (ILA, from 108 +/- 8 to 46 +/- 9%; AFF, from 108 +/- 14 to 58 +/- 8%), whereas no impairment was observed in sustained phases. Furthermore, the magnitude of the vasoconstriction caused by LNAME was greater at smaller vessel segments. Finally, the LNAME-induced inhibition of the sustained phase of ACH-induced vasodilation was greater as the vessel diameter decreased. CONCLUSIONS That the relative contribution of NO and EDHF differs, with a greater role of NO in the basal tone and ACH-induced vasodilation at smaller vascular segments of ILA and AFF.