VASCULAR REACTIVITY AND FLOW-PRESSURE CURVE IN ISOLATED KIDNEYS FROM RATS WITH N-NITRO-L-ARGININE METHYL ESTER-INDUCED HYPERTENSION

Objectives The purpose of this study was to determine the contribution of the functional changes in resistance vessels to the hypertension i nduced by chronic nitric oxide synthase inhibition in rats. Another go al of this study was to evaluate whether this model of hypertension is accompanied by changes in the activity of endothelium-derived hyperpo larizing factor (EDHF). Methods Hypertension was induced by long-term (6 weeks) oral administration of N-nitro-L-arginine methyl ester (L-NA ME; 75mg/100ml in the drinking fluid). Vascular reactivity to vasocons trictors (phenylephrine and barium chloride) and vasodilators (acetylc holine and nitroprusside) and the flow-pressure curve were examined in isolated perfused kidneys preparations. Vascular reactivity to vasoco nstrictors and the flow-pressure curve were studied under basal condit ions or after the infusion of L-arginine (100 mu mol/l). The activity of EDHF was evaluated by comparing the dose-response curves for acetyl choline obtained in potassium chloride- and phenylephrine-preconstrict ed preparations. Results Kidneys from L-NAME-induced hypertensive rats showed increased sensitivity to vasoconstrictors with a greater durat ion of the presser responses at high doses and markedly up-shifted flo w-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-tr eated rats also showed a decreased responsiveness to acetylcholine wit h an augmented reactivity to nitroprusside. The acetylcholine dose-res ponse curve was reduced in control preparations and greatly attenuated in L-NAME-treated preparations when the renal vasculature was precons tricted with potassium chloride. Conclusions The changes in vascular r eactivity observed in L-NAME-induced hypertensive rats may play an imp ortant role in the pathogenesis of this type of hypertension. Moreover , it is also suggested that longterm nitric oxide inhibition may be as sociated with increased activity of EDHF.