β-Adrenoceptor-mediated vascular relaxation in spontaneously hypertensive rats

Although the impairment of beta-adrenoceptor (β-AR)-induced vascular relaxation to isoprenaline has been extensively described, discrepancy persisted in the literature. In this work, we investigated β-AR-induced relaxation in spontaneously hypertensive and normotensive rats aorta. We attempted to determine β-AR subtypes involved in order to understand the conflicting data regarding the β-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 (α1-AR agonist). Then, cumulative concentration-relaxation curves (CCRC) to AR agonists were constructed. In intact aortic rings from both strains, isoprenaline (a nonselective β-AR agonist) (0.001-10 μM) induced similar concentration-dependent relaxations. CCRC was shifted to the right and upward in the presence of nadolol (a nonspecific β1 and β2-AR antagonist) (10 μM). 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 β1-AR antagonist). In endothelium-denuded rings, SR 58611A (a preferential β3-AR agonist) (0.1-30 μM) produced a very small relaxation in both strains. In WKY rats, CGP 12177 (CGP) (0.1-30 μM) and cyanopindolol (0.01-3 μM) (partial β3-AR and low-affinity-state β1-AR agonists with β1-AR and β2-AR antagonistic properties) produced endothelium-independent relaxations. CGP-induced effect was significantly inhibited by CGP 20712A (10 μM) or bupranolol (10 μM) (low-affinity-state β1-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 β1-AR. Gi protein overexpression and/or overstimulation may be possible factors that contribute to this alteration in hypertension.