Vascular reactivity and flow-pressure curve in isolated kidneys from rats with N-nitro-L-arginine methyl ester-induced hypertension.

The purpose of this study was to determine the contribution of the functional changes in resistance vessels to the hypertension induced by chronic nitric oxide synthase inhibition in rats. Another goal of this study was to evaluate whether this model of hypertension is accompanied by changes in the activity of endothelium-derived hyperpolarizing factor (EDHF). Hypertension was induced by long-term (6 weeks) oral administration of N-nitro-L-arginine methyl ester (L-NAME; 75 mg/100 ml in the drinking fluid). Vascular reactivity to vasoconstrictors (phenylephrine and barium chloride) and vasodilators (acetylcholine and nitroprusside) and the flow-pressure curve were examined in isolated perfused kidneys preparations. Vascular reactivity to vasoconstrictors and the flow-pressure curve were studied under basal conditions or after the infusion of L-arginine (100 mumol/l). The activity of EDHF was evaluated by comparing the dose-response curves for acetylcholine obtained in potassium chloride- and phenylephrine-preconstricted preparations. Kidneys from L-NAME-induced hypertensive rats showed increased sensitivity to vasoconstrictors with a greater duration of the pressor responses at high doses and markedly up-shifted flow-pressure curve in comparison with that obtained in control kidneys. These differences disappeared when the kidneys from control and L-NAME-treated rats were infused with L-arginine. The kidneys from L-NAME-treated rats also showed a decreased responsiveness to acetylcholine with an augmented reactivity to nitroprusside. The acetylcholine dose-response curve was reduced in control preparations and greatly attenuated in L-NAME-treated preparations when the renal vasculature was preconstricted with potassium chloride. The changes in vascular reactivity observed in L-NAME-induced hypertensive rats may play an important role in the pathogenesis of this type of hypertension. Moreover, it is also suggested that long-term nitric oxide inhibition may be associated with increased activity of EDHF.