Low-affinity state beta1-adrenoceptor (β
1-AR) was functionally expressed in some blood vessels
and was different from β
1, β
2 and β
3-AR. In rat aorta, low-affinity state β
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 β
1-AR agonists (CGP 12177, cyanopindolol or alprenolol)
and to NS 1619, a large conductance Ca
2+-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 β
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 β
1-AR effect only in SHRs groups. In 12 weeks old WKY rats, CGP 12177-induced relaxation was insensitive to glibenclamide, a
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channel blocker, but was reduced by TEA or iberiotoxin, two large conductance Ca
2+-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 β
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.
