Objective: To probe the potential influence of a high renal tubular level of angiotensin II on sodium reabsorption using angiotensin converting enzyme inhibitors and a non-peptide angiotensin antagonist.
Methods: Systemic arterial blood pressure, renal blood flow (RBF) and electrolyte and urinary excretion were measured in anesthetized uninephrectomized Wistar rats. Captopril (n = 12), ramiprilat (n = 10) or EXP 3174 (n = 9) was infused into the renal artery in graded doses to examine whether the threshold dose that increased RBF was lower than that which increased sodium excretion rate (Na+ excretion rate).
Results: Whereas ramiprilat (0.5-4 micrograms/kg/min intra-arterially) and EXP 3174 (0.5-4 micrograms/kg/min intra-arterially) decreased blood pressure in all but the lowest dose of 0.5 micrograms/kg/min, captopril (1-8 micrograms/kg/min intra-arterially) did not change blood pressure except for a slight effect with the two higher doses. These three agents increased RBF to about the same degree, between 6% and 18%, which was relatively large compared with the maximal vasodilator response achievable in the kidney with acetylcholine (30-37%). Captopril given intra-arterially had a more consistent effect on Na+ excretion rate than either ramiprilat or EXP 3174. An increase in Na+ excretion rate occurred with captopril ranging from 44% to 78%, whereas no significant change was obtained with the other drugs. The dose of captopril that increased RBF was the same as that which increased Na+ excretion rate. In those experiments in which ramiprilat resulted in an increase in Na+ excretion rate (five of 10 experiments), the effective dose was the same as that which increased RBF.
Conclusion: When administered by the intra-arterial route, captopril was more effective in increasing Na+ excretion rate than either ramiprilat or EXP 3174. Although the threshold dose of captopril and ramiprilat required to increase Na+ excretion rate and RBF was similar, suggesting blockade of a common angiotensin II pool, there was not a good correlation between these two effects.