Converting Enzyme Inhibition During Chronic Angiotensin II Infusion in Rats: Evidence Against a Nonangiotensin Mechanism

SUMMARY Interpretation of results obtained with angiotensin-converting enzyme inhibition in hypertensive patients has been obscured by the possibility of nonangiotensin-mediated mechanisms, particularly bradykinin potentiation. Using subcutaneous osmotic pumps to infuse angiotensin II chronically into conscious rats, we have compared the effects of converting enzyme inhibition (CEI) by oral captopril administration to those of dextrose. In this setting of constant angiotensin II levels, any apparent effects of CEI must be mediated by a nonangiotensin-related mechanism. Angiotensin II infusion at 30 ng/mln increased mean blood pressure by an average of 22 ram Hg. Following 7 days of CEI, effective blockade of converting enzyme was established both by a 10-fold elevation of vasodepressor sensitivity to exogenous bradykinin and a markedly decreased plasma converting enzyme activity. On the ninth day of angiotensin II infusion, mean arterial pressure, heart rate, and plasma renin activity were not different between the CEI and dextrose-treated groups. Similarly, blockade of angiotensin II by saralasin induced a comparable fall in blood pressure in both groups. Metabolic studies also revealed no long-term differences in water and food intake, weight change, or sodium and potassium metabolisms. These findings suggest that, in the continued presence of angiotensin II, there is no detectable hemodynamic or metabolic effect of chronic converting enzyme Inhibition, and therefore that bradykinin plays little or no role in its long-term antihypertensive action.