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 ac tivity in conscious, spontaneously hypertensive and Wistar-Kyoto rats durin g acute blood pressure lowering with nicardipine, enalaprilat and concomita nt nicardipine/enalaprilat administration. In a second experiment, we deter mined the effect of these drugs on arterial baroreflex control of lumbar sy mpathetic nerve activity. Methods Male spontaneously hypertensive and Wistar-Kyoto rats were instrume nted for continuous heart rate, blood pressure and lumbar sympathetic nerve activity recordings. Twenty-four hours later in conscious rats, nicardipin e, enalaprilat and enalaprilat/nicardipine were infused at sufficient doses to reduce mean arterial pressure by 20 mmHg over 30 min. In a second exper iment with the same drugs, baroreflex curves relating lumbar sympathetic ne rve activity to mean arterial pressure were analyzed using a logistic curve -fitting program. Results Blood pressure reductions induced by the three infusion protocols w ere similar in magnitude and profile. In both spontaneously hypertensive an d Wistar-Kyoto rats, nicardipine induced greater reflexive increases in lum bar sympathetic nerve activity than enalaprilat Pretreatment with a reduced dose of enalaprilat blunted subsequent nicardipine-induced sympathetic act ivation. Nicardipine tended to induce greater increases in the heart rate t han enalaprilat, but overall, the difference was not significant. Barorefle x sensitivity was similar regardless of drug class. Nicardipine significant ly increased minimum nerve activity compared with enalaprilat in spontaneou sly 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 co nverting enzyme inhibitor minimizes dihydropyridine-induced increases in sy mpathetic activity. This beneficial effect is attributable to suppression o f minimum sympathetic activity. These data suggest that coadministration of an angiotensin converting enzyme inhibitor may improve the long-term cardi ovascular benefit of dihydropyridine calcium channel blockers. J Hypertens 1999, 17:507-512 (C) Lippincott Williams & Wilkins.