Bradykinin B2 receptor-dependent enhancement of enalapril-evoked hypotension in ethanol-fed female rats.
Our previous studies showed that chronic ethanol feeding attenuates centrally (clonidine) evoked and potentiates peripherally (hydralazine) evoked hypotension in female rats. In this study, we investigated whether chronic ethanol (8 weeks, 5% wt/vol) alters hemodynamic responses elicited by angiotensin-converting enzyme (ACE) inhibition (enalapril) in telemetered female rats. Given the intimate interaction between ACE and bradykinin, studies were extended to investigate the role of bradykinin receptor (B2R) in ethanol-enalapril interaction. Compared with pair-fed controls, ethanol-fed female rats exhibited (1) higher renal expressions of ACE and B2R proteins and angiotensin II levels and (2) lower blood pressure. Pharmacological inhibition of ACE and B2R supports functional role for the higher levels of these 2 proteins in ethanol-fed rats because enalapril (10 mg/kg, intraperitoneally) caused significantly greater hypotensive response in ethanol-fed rats than in control rats. Further, blockade of B2R with bradyzide (2 mg/kg, intraperitoneally) abrogated the enhanced hypotensive effect of enalapril in ethanol-fed rats but had no effect on enalapril-evoked hypotension in control rats. Finally, enalapril enhancement of spontaneous baroreflex sensitivity (BRS) in control was absent in ethanol-fed rats. These findings demonstrate that chronic ethanol produces B2R-dependent enhancement of the hypotensive response elicited by enalapril and abrogates enalapril-evoked enhancement of spontaneous baroreflex response in female rats.
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Mahmoud M
MM
El-Mas
Abdel A
AA
Abdel-Rahman
D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D007022:Hypotension / Q000503:physiopathology*; D007703:Peptidyl-Dipeptidase A / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D013686:Telemetry / Q000379:methods
D043782:Receptor, Bradykinin B2; D006830:Hydralazine; D000431:Ethanol; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D003000:Clonidine; D001920:Bradykinin