Impaired nitric oxide- and endothelium-derived hyperpolarizing factor-dependent dilation of renal afferent arteriole in Dahl salt-sensitive rats

Background and Aims: We previously demonstrated that acetylcholine elicited nitric oxide-dependent sustained and endothelium-derived hyperpolarizing factor (EDHF)-dependent transient dilation of afferent arterioles. The present study examined whether free radicals interacted with nitric oxide-dependent and EDHF-dependent vasodilator mechanisms in renal microvessels of salt-sensitive hypertension, using the isolated perfused hydronephrotic kidney. Methods and Results: Following the pretreatment with indomethacin (100 mumol/L) with or without nitro-L-arginine methylester (100 mumol/L), the effect of acetylcholine on noradrenaline (0.3 mumol/L)-induced constriction was evaluated in kidneys from Dahl salt-sensitive and salt-resistant rats. Although acetylcholine (0.01-10 mumol/L) caused dose-dependent and sustained vasodilation of afferent arterioles, attenuated dilation was observed in Dahl salt-sensitive rats, compared with that in salt-resistant rats (58 +/- 4 vs 101 +/- 11% reversal at 10 mumol/L acetylcholine). In the presence of nitro- L-arginine methylester, acetylcholine elicited only transient dilation, with vasodilator response blunted in Dahl salt-sensitive rats (64 +/- 4 vs 100 +/- 9% reversal at 10 mumol/L acetylcholine). Furthermore, chronic (8-10 weeks) treatment with tempol caused partial restoration of acetylcholine (10 mumol/L)-induced sustained arteriolar dilation (71 +/- 3% reversal), but complete reversal of transient dilation (92 +/- 4% reversal). Finally, acute treatment with tempol not only improved the sustained component of the acetylcholine-induced dilation but also restored the impaired responsiveness of transient dilation in Dahl salt-sensitive rats. Conclusion: Both sustained (nitric oxide-mediated) and transient (EDHF-mediated) components of acetylcholine-induced afferent arteriolar dilation were attenuated in Dahl salt-sensitive rats, which was attributed, in part, to enhanced free radical activity. A reversal of the sustained and transient vasodilation by the acute tempol treatment suggests possible interaction between free radicals and EDHF as well as increased bioavailability of nitric oxide.