Low-affinity state beta1-adrenoceptor-induced vasodilation in SHR-

Authors
M. Y. Mallem, O. Reculeau, O. Le Coz, M. Gogny, J.-C. Desfontis.


Lab
Ecole Nationale Vétérinaire, UPSP 5304 de Physiopathologie Animale et de Pharmacologie Fonctionnelle, Nantes, France.

Journal
Peptides

Abstract
Low-affinity state beta1-adrenoceptor (_1-AR) was functionally expressed in some blood vessels and was different from _1, _2 and _3-AR. In rat aorta, low-affinity state _1-AR activation produced an endothelium-independent relaxation which was impaired in spontaneously hypertensive rats (SHRs). In the present work, we investigated whether renin–angiotensin system was involved in this alteration by evaluating the effects of enalapril, an angiotensin converting enzyme (ACE) inhibitor or losartan, an AT1 angiotensin receptor antagonist. Cumulative concentration–response curves to low-affinity state _1-AR agonists (CGP 12177, cyanopindolol or alprenolol) and to NS 1619, a large conductance Ca2+-activated K+ channels (BK) agonist were performed in denuded aortic rings isolated from control or treated Wistar Kyoto (WKY) rats or SHRs in different experimental conditions. The low-affinity state _1-AR-mediated aortic vasodilation was impaired in 5 and 12 weeks old SHRs when compared to age-matched WKY. Twelve days enalapril (5 mg/kg/day) or losartan (15 mg/kg/day) treatments reduced systolic blood pressure (SBP) only in 12 weeks old SHRs whereas no significant change was observed in other groups. These treatments improved low-affinity state _1-AR effect only in SHRs groups. In 12 weeks old WKY rats, CGP 12177-induced relaxation was insensitive to glibenclamide, a channel blocker, but was reduced by TEA or iberiotoxin, two large conductance Ca2+-activated K+ channel (BK) blockers. The impairment of NS 1619-induced vasodilation in both 5 and 12 weeks old SHRs was restored by enalapril or losartan. These results suggested that improvement of the low-affinity state _1-AR-mediated vasodilation in 5 and 12 weeks old SHRs could be attributed to enhanced BK channels-induced hyperpolarization in SHRs independently of lowering of SBP.

BIOSEB Instruments Used:
Non Invasive Pressure Measurement (LE5001)

DEMANDE DE PUBLICATION

Merci de votre intérêt pour notre gamme de produits et de votre demande pour cette publication qui vous sera envoyée si l'équipe de recherche et la revue le permettent. Notre équipe commerciale vous contactera dans les plus brefs délais.