Enalaprilat blunts reflexive increases in cardiac interstitial norepinephrine in conscious rats

Objective We have reported that acute administration of enalaprilat an angi otensin converting enzyme inhibitor, induces less reflexive increase in lum bar sympathetic nerve activity in spontaneously hypertensive rats (SHRs) th an nicardipine, a dihydropyridine calcium-channel blocker. The current stud y was conducted to determine if angiotensin converting enzyme inhibitors li kewise suppress cardiac sympathetic activation. Design Cardiac interstitial levels of norepinephrine were measured in fully conscious SHRs before and after acute blood pressure lowering with enalapr ilat or nicardipine. Methods Microdialysis probes were inserted into the left ventricular wall o f SHRs. Twenty-four to 48 hours postimplantation, myocardial interstitial f luid was collected in fully conscious rats during a 60-min baseline period. Mean arterial pressure was lowered 20 mmHg with intravenous infusion of en alaprilat or nicardipine. During continuous enalaprilat or nicardipine infu sion, myocardial interstitial fluid was again collected. Norepirephrine lev els were assayed in the perfusate. Conclusions Enalaprilat-induced reduction in mean arterial pressure did not significantly increase cardiac interstitial norepinephrine levels. In cont rast, nicardipine-induced reduction in blood pressure was associated with a significant increase in interstitial norepinephrine levels. These results indicate that enalaprilat suppresses reflexive sympathetic activation of th e heart during acute blood pressure lowering. These results may be clinical ly relevant in that reductions in end-organ sympathetic stimulation may enh ance the long-term cardiovascular benefit of angiotensin converting enzyme inhibitors. (C) 2001 Lippincott Williams & Wilkins.