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 μg/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 α1 or α2-adrenoceptors were blocked. Furthermore, imidaprilat (100 μg/kg, i.v.) suppressed these reduced responses. When the reduced basal blood pressure was restored by vasopressin infusion, imidaprilat and enalaprilat (both at 100 μg/kg, i.v.) did not suppress the responses to ES and exogenous α-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 α-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.
