Interference with the autonomic nervous system by the converting enzyme inhibitor ramipril in conscious spontaneously hypertensive rats.
The interaction of the converting enzyme inhibitor (CEI) ramipril with sympathetic neurotransmission and the baroreceptor reflex (BRR) was investigated in conscious stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto (WKY) controls. Intravenous (i.v.) injection of ramipril (100 micrograms) attenuated the pressor responses to i.v. noradrenaline (NA) in SHRSP and WKY rats. Ganglionic blockade was performed with pentolinium (10 mg/kg i.v.), and blood pressure (BP) was subsequently supported with i.v. NA (1 microgram/min), angiotensin II (ANG II, 500 ng/min), or NA plus a subpressor dose (0.1 ng/min) of ANG II. Intravenous injection of ramiprilat (100 micrograms) significantly decreased NA-supported BP in SHRSP and WKY rats for more than 30 min, but did not lower BP in rats supported with ANG II or with NA plus a subpressor dose of ANG II. In SHRSP and WKY rats pretreated intracerebroventricularly (i.c.v.) with ramiprilat (0.5 microgram/min for 30 min), the slope of the BRR curve between increases in systolic BP and prolongation in pulse interval following bolus i.v. injections of methoxamine (10-100 micrograms/kg) was steeper than in vehicle-pretreated controls. In contrast, i.v. pretreatment with the same dose of the CEI did not increase BRR sensitivity. Our data in conscious animals demonstrate that CEI can interfere acutely with the autonomic nervous system through postsynaptic inhibition of neurotransmission and sensitization of the baroreceptor reflex. The relevance of this mechanisms for the chronic antihypertensive actions of CEI remains to be established.
Moursi
M
M
German Institute for High Blood Pressure Research, University of Heidelberg, F.R.G.
el-Dakhakhny
M
M
Schölkens
B A
BA
Unger
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D005260:Female; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects; D017257:Ramipril; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D017257:Ramipril