Pretreatment with enalaprilat blunts nicardipine-induced sympathetic activation in spontaneously hypertensive and Wistar-Kyoto rats.
OBJECTIVE
We measured changes in heart rate and lumbar sympathetic nerve activity in conscious, spontaneously hypertensive and Wistar-Kyoto rats during acute blood pressure lowering with nicardipine, enalaprilat and concomitant nicardipine/enalaprilat administration. In a second experiment, we determined the effect of these drugs on arterial baroreflex control of lumbar sympathetic nerve activity.


METHODS
Male spontaneously hypertensive and Wistar-Kyoto rats were instrumented for continuous heart rate, blood pressure and lumbar sympathetic nerve activity recordings. Twenty-four hours later in conscious rats, nicardipine, enalaprilat and enalaprilat/nicardipine were infused at sufficient doses to reduce mean arterial pressure by 20 mmHg over 30 min. In a second experiment with the same drugs, baroreflex curves relating lumbar sympathetic nerve activity to mean arterial pressure were analyzed using a logistic curve-fitting program.


RESULTS
Blood pressure reductions induced by the three infusion protocols were similar in magnitude and profile. In both spontaneously hypertensive and Wistar-Kyoto rats, nicardipine induced greater reflexive increases in lumbar sympathetic nerve activity than enalaprilat Pretreatment with a reduced dose of enalaprilat blunted subsequent nicardipine-induced sympathetic activation. Nicardipine tended to induce greater increases in the heart rate than enalaprilat, but overall, the difference was not significant Baroreflex sensitivity was similar regardless of drug class. Nicardipine significantly increased minimum nerve activity compared with enalaprilat in spontaneously hypertensive rats (similar trends were observed in Wistar-Kyoto rats). This increase in minimum nerve activity was blunted by enalaprilat


CONCLUSIONS
These results indicate that pretreatment with an angiotensin converting enzyme inhibitor minimizes dihydropyridine-induced increases in sympathetic activity. This beneficial effect is attributable to suppression of minimum sympathetic activity. These data suggest that co-administration of an angiotensin converting enzyme inhibitor may improve the long-term cardiovascular benefit of dihydropyridine calcium channel blockers.
Vascular Biology and Hypertension Program, University of Alabama at Birmingham, USA. dcalhoun@uab.edu
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004347:Drug Interactions; D015773:Enalaprilat / Q000494:pharmacology*; D008161:Lumbosacral Region; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000959:Antihypertensive Agents; D009529:Nicardipine; D015773:Enalaprilat