Chronic central administration of enalaprilat lowers blood pressure in stroke-prone spontaneously hypertensive rats.
Earlier studies on the cardiovascular effects of intracerebroventricular (i.c.v.) administration of angiotensin converting enzyme (ACE) inhibitors implicate angiotensin II (AII) present in the central nervous system in the pathogenesis of hypertension. We have now examined whether central AII contributes to the maintenance of established hypertension in adult stroke-prone spontaneously hypertensive rats (SHRSP). The ACE inhibitor, enalaprilat, was infused i.c.v. for two weeks at a rate of 5 micrograms/h via osmotic minipumps. Control rats were either untreated or infused with saline. Mean arterial pressure (MAP), measured via an indwelling catheter, fell within 24 h in the enalaprilat-treated rats and remained at least 30 mmHg lower than in controls. This difference persisted after intravenous (i.v.) administration of a vasopressin (AVP) antagonist but was eliminated by subsequent ganglion blockade with i.v. pentolinium. Without prior administration of the AVP antagonist, however, the reductions of MAP after pentolinium were smaller. The reduction was still attenuated in treated rats compared with controls but there was a significant difference in the residual MAP. Circulating catecholamine levels were reduced by central ACE inhibition. However, pressor responsiveness to i.v. phenylephrine was unaffected. The results suggest that, in SHRSP, central ACE inhibition lowers blood pressure by reducing sympathetic outflow, implying that central AII has a tonic sympathoexcitatory effect in this strain.
Jablonskis
L T
LT
Division of Human Nutrition, Commonwealth Scientific and Industrial Research Organisation, Adelaide, Australia.
Rogers
P F
PF
Lungershausen
Y K
YK
Howe
P R
PR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D004195:Disease Models, Animal; D015773:Enalaprilat / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood; D006973:Hypertension / Q000188:drug therapy; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010425:Pentolinium Tartrate / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains
D010425:Pentolinium Tartrate; D015773:Enalaprilat; D009638:Norepinephrine; D004837:Epinephrine