We investigated the acute and chronic effects of converting enzyme inhibitors (captopril or enalapril) and of angiotensin II receptor blockade (DuP 753) on rapid (30-minute) baroreceptor resetting elicited by a prompt and sustained hypertensive response provoked by aortic constriction. Pressure-nerve activity curves, pressure at 50% of maximal baroreceptor activity, baroreceptor gain (slope of the curve), and systolic threshold pressure for baroreceptor activation were determined as indexes of baroreceptor function. A slight fall in mean arterial pressure after acute treatment with the converting enzyme inhibitor or DuP 753 was accompanied by a partial leftward curve shift, which is associated with a partial threshold shift and increase in gain. A maintained hypertensive stimulus caused a partial rightward curve shift and partial (49% to 56%) threshold shift to hypertensive levels in both acutely treated and control rats. The hypertensive stimulus provoked a partial rightward curve shift and complete (88% to 94%) threshold shift to hypertensive levels in chronically treated rats. 8 have demonstrated that as Ang II concentration increases, the pressurenerve activity curves shift in a parallel manner to higher pressures, requiring a substantially higher pressure threshold for baroreceptor activation. Accordingly, endogenous vasoactive peptides such as Ang II might also modulate rapid resetting. Changes in pressure threshold are linearly related to changes in conditioning pressure over a wide range, 11 and rapid resetting is usually recognized as partial because the magnitude of the shift in pressure threshold is approximately 50% or less 61113 of the magnitude of change in conditioning pressure. Nevertheless, when rapid resetting was driven to hypotensive levels with the conditioning pressure under the influence of an antihypertensive agent, the baroreceptors totally adapted within 15 minutes. Correspondence to Dr H61io C. Salgado, Department of Physiology, School of Medicine, USP, 14049-900 Ribeirao Preto, SP, Brazil.To our knowledge the effect of ACE inhibition on rapid baroreceptor resetting has not yet been investigated in any hypertensive model. Therefore, we evaluated in the present study the extent of rapid (30-minute) resetting elicited by a prompt and sustained rise in arterial pressure in nonnotensive rats treated acutely (15 minutes) or chronically (7 days) with ACE inhibitors, captopril or enalapril, and an ATi receptor antagonist, DuP 753. We also investigated the role played by bradykinin potentiation on rapid baroreceptor resetting during blockade of ACE.
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MethodsExperiments were performed on anesthetized (thiopental sodium, 40 mg/kg IP) normotensive male Wistar rats (250 to 300 g) in accordance with the guiding principles of the American Physiological Society. Catheters were placed into the right common carotid artery for measurement of arterial pressure, the right femoral artery for withdrawal and reinfusion of blood, and the right femoral vein for the administration of drugs. A pneuma...