ANF(99-126) (1 microgram/kg/min x 30 min iv) lowered BP from 198 +/- 3 to 140 +/- 4 mmHg (P less than .05; N = 7), in association with marked diuresis (372.2 +/- 33.9 vs 48.2 +/- 11.5 microliters/kg/min in the control) and natriuresis (62.7 +/- 6.4 vs 6.6 +/- 1.7 muEq/kg/min) in anesthetized SHR. Concomitantly, great increases in plasma cGMP levels and urinary cGMP excretion occurred. Elevation in plasma cGMP due to ANF persisted in SHR with bilateral nephrectomy. SNP (4 micrograms/kg/min x 30 min iv) decreased BP from 192 +/- 3 to 158 +/- 5 mmHg (P less than .05; N = 7). In contrast to ANF, this occurred without significant changes in urine and sodium excretion; alterations in plasma and urinary cGMP were also absent. Furthermore, 8-Br-cGMP (0.3 mg/kg/min x 30 min iv) also lowered BP from 164 +/- 9 to 129 +/- 7 mmHg (P less than .05; N = 6) in the absence of diuresis (8.5 +/- 1.3 vs 19.8 +/- 4.1 microliters/kg/min). Intravenous infusion of 8-Br-cAMP at the same rate did not affect BP and produced a modest but significant increase in sodium and water excretion. Our results indicate that the renal excretory responses to exogenous cGMP or SNP differ from those to ANF. The findings are consistent with a mediating role of cGMP in the vascular but not the renal effects of ANF, since at equally effective hypotensive doses both SNP and 8-Br-cGMP failed to register any significant renal excretory effects.