The aim of this study was to assess the effects of acute or prolonged increases of ANG II on nitric oxide synthase (NOS) activities and protein expression in mesenteric resistance vessels, left ventricle, renal cortex, and renal medulla. The response of NOS activities to ANG II is compared with that induced by phenylephrine. ANG II or phenylephrine were infused over either 3 h or 3 days to conscious rats. NOS activity was examined by measuring the rate of conversion of L-[14C]arginine to L-[14C]citrulline. Protein levels of endothelial (e) and neuronal (n) NOS were determined by Western blot analysis. Arterial pressure (AP) increased (P < 0.05) during acute and prolonged ANG II infusion. Ca2+-dependent NOS activity values (pmol of citrulline x min(-1) x g wet wt(-1)) for control rats were 21 +/- 9 in mesenteric arteries, 13 +/- 7 in left ventricle, 14 +/- 8 in renal cortex, and 411 +/- 70 in renal medulla. Acute ANG II infusion increased (P < 0.05) Ca2+-dependent NOS activity in renal cortex and renal medulla (81 +/- 18 and 611 +/- 48, respectively), but no differences were found in mesenteric arteries and left ventricle with respect to control rats. In contrast to the renal changes in NOS activity, acute ANG II infusion did not modify eNOS or nNOS expression in any of the tissues examined. Prolonged ANG II infusion increased (P < 0.05) Ca2+-dependent NOS activity in mesenteric arteries (70 +/- 17), renal cortex (104 +/- 31), and left ventricle (49 +/- 8) and did not elicit changes in renal medulla. After a prolonged ANG II infusion, eNOS and nNOS levels increased in all tissues examined with the exception of eNOS in the mesenteric arteries and nNOS in the left ventricle, which were not altered. Acute and prolonged phenylephrine infusion elevated AP to a similar extent as ANG II but only elicited significant increments of Ca2+-dependent NOS activity in renal cortex. These data indicate that acute and prolonged elevations in ANG II upregulate Ca2+-dependent NOS activity and protein expression in different tissues related to the control of blood pressure. However, these ANG II effects are heterogeneous with respect to the tissue implicated, the time course of the stimulation, and the NOS isoform involved. Phenylephrine only induces a significant elevation of Ca2+-dependent NOS activity in renal cortex.