No relation of the suppressive effect on the sympathetic nervous system to the acute hypotension caused by imidapril and enalapril.
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 micrograms/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 alpha 1- or alpha 2-adrenoceptors were blocked. Furthermore, imidaprilat (100 micrograms/kg, i.v.) suppressed these reduced responses. When the reduced basal blood pressure was restored by vasopressin infusion, imidaprilat and enalaprilat (both at 100 micrograms/kg, i.v.) did not suppress the responses to ES and exogenous alpha-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 alpha-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.
Ogiku
N
N
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Sumikawa
H
H
Ishida
R
R
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003655:Decerebrate State; D004558:Electric Stimulation; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology*; D015773:Enalaprilat / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013116:Spinal Cord / Q000473:pathology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D048289:Imidazolidines; D014667:Vasopressins; D004656:Enalapril; C065166:imidapril; D015773:Enalaprilat; C078006:imidaprilat; D009638:Norepinephrine; D004837:Epinephrine