We examined the role of free radicals in renal microvascular tone induced by various vasoactive stimuli. Isolated perfused rat hydronephrotic kidneys were used for direct visualization of renal microcirculation. The effect of tempol on angiotensin II-, norepinephrine-, KCl-, and pressure-induced afferent arteriolar constriction was evaluated. Under angiotensin II-induced constriction, tempol (3 mmol/L) caused 57 ± 8% dilation of afferent arterioles. In contrast, tempol elicited only 38 ± 8% and 26 ± 9% dilation of norepinephrine- and KCl-induced constriction. Similarly, myogenic response induced by elevating renal arterial pressure from 80 to 180 mmHg was resistant to the vasodilator action of tempol (22 ± 7% inhibition). Furthermore, tempol failed to reverse nitro-L-arginine methylester-induced afferent constriction, nor had vasodilator effect on the angiotensin II-induced constriction in the presence of nitro-L-arginine methylester. In contrast, nitroprusside elicited marked vasodilation of angiotensin II- (97 ± 5% reversal) and norepinephrine-induced afferent constriction (89 ± 6% reversal), but had less effect on KCl- (46 ± 8% reversal) and pressure-induced constriction (26 ± 9% reversal). These different actions were also observed when polyethylene-glycolated superoxide dismutase was used as an antioxidant. In conclusion, the role of free radicals in afferent arteriolar tone varies, depending on the underlying vasoconstrictor stimuli, with greater contribution of free radicals to angiotensin II-induced constriction. The heterogeneity in the responsiveness to free radical scavengers is attributed to both magnitude of free radicals produced and sensitivity of the underlying vasoconstrictors to nitric oxide.
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