No Relation of the Suppressive Effect on the Sympathetic Nervous System to the Acute Hypotension Caused by Imidapril and Enalapril

Abstract

ABSTRACT-To investigate the involvement of the sympathoinhibitory effect of imidapril and enalapril in their antihypertensive effect at a clinically reasonable dose, we studied whether some responses induced by the stimulation of the sympathetic nervous system (SNS) were affected by intravenous administration of imidaprilat and enalaprilat in curarized pithed spontaneously hypertensive rats. Imidaprilat and enalaprilat (both at 100 pg/kg, i.v.), which are active metabolites of imidapril and enalapril, respectively, suppressed the pressor responses to electrical stimulation (ES) of the spinal cord (T1 L7) and exogenous noradrenaline (NA). The pressor responses to NA were significantly suppressed after either a1 or a2-adrenoceptors were blocked. Furthermore, imidaprilat (100 ,ug/kg, i.v.) suppressed these reduced responses. When the reduced basal blood pressure was restored by vasopressin infusion, imidaprilat and enalaprilat (both at 100 pg/kg, i.v.) did not suppress the responses to ES and exogenous a-adrenoceptor agonists. They affected neither basal plasma concentrations of NA and adrenaline nor ES-induced increase of these catecholamines. These results suggest that the suppressive effects of imidaprilat and enalaprilat on the pressor responses to ES and a-adrenoceptors agonists are apparently observed in pithed SHR because of a reduction of vascular tone and that imidapril and enalapril do not lower the blood pressure through suppressing SNS.

Cardiometabolic and Inflammatory Benefits of Sympathetic Down-Regulation with Zamicastat in Aged Spontaneously Hypertensive Rats

“…The aim of the present study was to evaluate the effect of prolonged zamicastat-induced DBH inhibition beyond a BP decrease. For that purpose, we used male aged SHRs, a well-defined preclinical model for human essential hypertension and heart failure that has been widely used in the study and development of novel antihypertensive drugs, − and age-matched Wistar Kyoto rats (WKYs) as normotensive counterparts.…”