We evaluated pressure-dependent stimulation of renin release in rats with sustained hypertension induced by chronic blockade of nitric oxide synthase with N omega-nitro-L-arginine methyl ester (L-NAME) for 5 to 7 days. Rats were anesthetized and catheters were inserted into the carotid artery and abdominal aorta for measurement of arterial pressures. An adjustable snare was placed around the suprarenal aorta, and this snare was tightened to reduce renal perfusion pressure. Pressure-dependent renin release was evaluated in hypertensive rats by reducing renal perfusion pressure to 125, 85, and 65 mm Hg. Renin release was also evaluated in normotensive control rats at these same pressures. Basal systemic arterial pressures averaged 159 +/- 3 and 124 +/- 4 mm Hg (P < .001), respectively, in the L-NAME-treated (n = 22) and normotensive control (n = 18) rats. Basal plasma renin activity was lower in L-NAME than control rats (5.0 +/- 0.3 versus 9.5 +/- 1.3 U, P < .01), and plasma renin activity was markedly attenuated at all comparable levels of renal perfusion pressure. Maximal plasma renin activity levels were achieved at perfusion pressures reduced to 65 mm Hg, and plasma renin activity averaged 14 +/- 2 and 34 +/- 7 U (P < .01) in L-NAME hypertensive and control rats, respectively. However, infusion of the nitric oxide donor sodium nitroprusside similarly stimulated plasma renin activity levels to 39 +/- 3 and 45 +/- 3 U (P > .05), in the hypertensive and normal control groups, respectively. Overall, these findings are consistent with the hypothesis that prolonged L-NAME administration attenuates pressure-dependent renin release by inhibiting nitric oxide formation, which may function as a paracrine mechanism inversely linking renal perfusion pressure with the stimulation of renin release.