PLASMA-RENIN ACTIVITY AND THE RENAL RESPONSE TO NITRIC-OXIDE SYNTHESIS INHIBITION

Inhibition of systemic endothelium-derived relaxing factor (EDRF) synthesis with L-N(w)-nitroarginine (L-NAME) results in decreased RBF, which can be reversed by acute blockade of angiotensin II (AII). Because AII is particularly elevated in the renal circulation, it was hypothesized that the degree of renal vasoconstriction produced by L-NAME in Inactin-anesthetized rats is related to PRA. To test this, PRA was chronically increased or suppressed by the manipulation of dietary sodium (eating 0.03% sodium chow or deoxycorticosterone acetate plus drinking 1% NaCl, respectively). After 10 days, rats were anesthetized for determination of blood pressure (BP) and RBF before and after L-NAME (10 mg/kg body wt). In rats with high PRA (61.6 +/- 10.4 ng of angiotensin I (AI)/mL/h; N = 8), L-NAME increased BP by 29 +/- 2 mm Hg (from 110 +/- 4 to 139 +/- 5 mm Hg; P < 0.001), decreased RBF by 27% (from 7.9 +/- 0.3 to 5.8 +/- 0.3 mL/min/g kidney wt; P < 0.001), and increased renal vascular resistance (RVR) by 67% (from 14.5 +/- 0.9 to 24.2 +/- 1.1 resistance units (RU); P < 0.001). When rats with high PRA (N = 8) were treated with 10 mg/kg body wt of DuP 753, an AII receptor antagonist, L-NAME similarly increased BP by 30 +/- 5 mm Hg (from 81 +/- 3 to 111 +/- 5; P < 0.001) but RBF did not change and RVR increased by only 31% (from 10.9 +/- 0.8 to 13.3 +/- 0.7 RU; P < 0.005). In rats with low PRA (0.8 +/- 0.1 ng of Al/h/mL; N = 8), L-NAME increased BP by 23 +/- 2 mm Hg (from 104 +/- 4 to 127 +/- 3 mm Hg; P < 0.001); there was, however, no decrease in RBF, whereas RVR increased by only 30% (from 16.2 +/- 0.9 to 21.1 +/- 1.5 RU; P < 0.005). Therefore, neither chronically suppressing AII nor acutely inhibiting it with DuP 753 reduced the systemic pressor response, whereas either manipulation greatly attenuated the decrease in RBF produced by L-NAME. These results suggest that, in the anesthetized rat, the renal but not the systemic response to EDRF synthesis inhibition is predominantly mediated by AII, suggesting that a particular balance between EDRF and AII maintains the renal circulation.