Enalaprilat blunts reflexive increases in cardiac interstitial norepinephrine in conscious rats.
OBJECTIVE
We have reported that acute administration of enalaprilat, an angiotensin converting enzyme inhibitor, induces less reflexive increase in lumbar sympathetic nerve activity in spontaneously hypertensive rats (SHRs) than nicardipine, a dihydropyridine calcium-channel blocker. The current study was conducted to determine if angiotensin converting enzyme inhibitors likewise suppress cardiac sympathetic activation.


METHODS
Cardiac interstitial levels of norepinephrine were measured in fully conscious SHRs before and after acute blood pressure lowering with enalaprilat or nicardipine.


METHODS
Microdialysis probes were inserted into the left ventricular wall of SHRs. Twenty-four to 48 hours post-implantation, myocardial interstitial fluid was collected in fully conscious rats during a 60-min baseline period. Mean arterial pressure was lowered 20 mmHg with intravenous infusion of enalaprilat or nicardipine. During continuous enalaprilat or nicardipine infusion, myocardial interstitial fluid was again collected. Norepinephrine levels were assayed in the perfusate.


CONCLUSIONS
Enalaprilat-induced reduction in mean arterial pressure did not significantly increase cardiac interstitial norepinephrine levels. In contrast, 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 the heart during acute blood pressure lowering. These results may be clinically relevant in that reductions in end-organ sympathetic stimulation may enhance the long-term cardiovascular benefit of angiotensin converting enzyme inhibitors.
Calhoun
D A
DA
Vascular Biology and Hypertension Program, University of Alabama, Birmingham 35294, USA. dcalhoun@uab.edu
Wei
C C
CC
Zhu
S
S
Bradley
W E
WE
Dell'Italia
L J
LJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009529:Nicardipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D012018:Reflex / Q000187:drug effects* / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D009529:Nicardipine; D015773:Enalaprilat; D009638:Norepinephrine