Low-affinity state beta1-adrenoceptor-induced vasodilation in SHR.
Low-affinity state beta1-adrenoceptor (beta1-AR) was functionally expressed in some blood vessels and was different from beta1, beta2 and beta3-AR. In rat aorta, low-affinity state beta1-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 beta1-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 beta1-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 beta1-AR effect only in SHRs groups. In 12 weeks old WKY rats, CGP 12177-induced relaxation was insensitive to glibenclamide, a K(ATP)+ 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 beta1-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.
Mallem
Mohamed Yassine
MY
UPSP 5304 de Physiopathologie Animale et de Pharmacologie Fonctionnelle, Ecole Nationale Vétérinaire, Nantes, France.
Reculeau
Olivier
O
Le Coz
Olivier
O
Gogny
Marc
M
Desfontis
Jean-Claude
JC
D058665:Adrenergic beta-1 Receptor Agonists; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D058665:Adrenergic beta-1 Receptor Agonists; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; C047975:cyanopindolol; D004656:Enalapril; D000526:Alprenolol; D010869:Pindolol; D019808:Losartan; C033394:CGP 12177