Beta-adrenoceptor-mediated vascular relaxation in spontaneously hypertensive rats.

Although the impairment of beta-adrenoceptor (beta-AR)-induced vascular relaxation to isoprenaline has been extensively described, discrepancy persisted in the literature. In this work, we investigated beta-AR-induced relaxation in spontaneously hypertensive and normotensive rats aorta. We attempted to determine beta-AR subtypes involved in order to understand the conflicting data regarding the beta-AR-induced vasodilation to isoprenaline. Aortic rings isolated from 12-week-old Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were placed in organ baths and constricted with phenylephrine (alpha1-AR agonist). Then, cumulative concentration-relaxation curves (CCRC) to AR agonists were constructed. In intact aortic rings from both strains, isoprenaline (a nonselective beta-AR agonist) (0.001-10 microM) induced similar concentration-dependent relaxations. CCRC was shifted to the right and upward in the presence of nadolol (a nonspecific beta1 and beta2-AR antagonist) (10 microM). After endothelium removal, the response to isoprenaline was partly inhibited in WKY rats, but was strongly inhibited in SHRs. In WKY rats, isoprenaline-induced endothelium-independent relaxation was not modified in the presence of nadolol but was inhibited in the presence of CGP 20712A (low-affinity-state beta1-AR antagonist). In endothelium-denuded rings, SR 58611A (a preferential beta3-AR agonist) (0.1-30 microM) produced a very small relaxation in both strains. In WKY rats, CGP 12177 (CGP) (0.1-30 microM) and cyanopindolol (0.01-3 microM) (partial beta3-AR and low-affinity-state beta1-AR agonists with beta1-AR and beta2-AR antagonistic properties) produced endothelium-independent relaxations. CGP-induced effect was significantly inhibited by CGP 20712A (10 microM) or bupranolol (10 microM) (low-affinity-state beta1-AR antagonists). In SHRs, similarly to the impaired endothelium-independent relaxation to isoprenaline, endothelium-independent relaxations to CGP and cyanopindolol were greatly blunted. These relaxations were not modified in the presence of CGP 20712A. In endothelium-denuded rings pretreated with pertussis toxin, CGP-induced relaxation was not modified in WKY rats, but was partly restored in SHRs. In conclusion, these results showed, that in 12-week-old SHRs, the endothelium-independent component of the relaxation to isoprenaline was impaired, and this impairment could involve the low-affinity-state beta1-AR. G(i) protein overexpression and/or overstimulation may be possible factors that contribute to this alteration in hypertension.