The present study was undertaken to investigate the functional expression of atypical β-adrenoceptors (β-AR) in aorta from Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) at 12 weeks old.

Rats were anaesthetised with pentobarbital (30 mg kg^-1 I.P.) and thoracic aortic rings were removed, isolated and suspended on stainless-steel wires in 5 ml organ baths containing Krebs solution (Mallem et al. 2002). Rings were constricted with phenylephrine (α₁-AR agonist) and cumulative concentration- relaxation curves to atypical β-AR agonists were constructed. Results are expressed as the percentage of relaxation from the steady-state contraction level induced by phenylephrine (mean ± S.E.M. of n experiments).

In intact WKY aorta, CGP 12177 (CGP) or cyanopindolol (partial β₃-AR and atypical β-AR agonists with β₁/β₂-AR antagonistic properties) produced concentration-dependent relaxation (pD₂ = 6.17 ± 0.05; E_max = 95.9 ± 1% n = 5, for cyanopindolol). In order to determine the role of the endothelium and nitric oxide (NO) in atypical β-AR-mediated relaxation, responses to CGP or to cyanopindolol were evaluated in endothelium-denuded aorta or after pretreatment with a NO synthase inhibitor (L-NMMA, 100 µM). Both CGP and cyanopindolol-induced relaxation were not modified by endothelium removal or after L-NMMA treatment. The CGP-induced endothelium-independent relaxation was not altered in the presence of 10 µM nadolol (β₁/β₂-AR antagonist) or 1 µM SR 59230 (β₃-AR antagonist) but was significantly reduced in the presence of CGP 20712A or bupranolol (atypical β-AR antagonists in higher concentrations) (P < 0.05 by ANOVA). The involvement of the cyclic AMP-dependent pathway in response to atypical β-AR agonists was evaluated in denuded aortic rings of WKY aorta. Endothelium-independent relaxation to CGP was inhibited by SQ 22536 or MDL 12330A, non-selective adenylyl cyclase inhibitors (P < 0.05 by ANOVA). In SHR aortic rings, CGP or cyanopindolol produced concentration-dependent relaxation similar to that obtained in WKY aorta (pD₂ = 6.09 ± 0.05; E_max = 96 ± 1% n = 5, for cyanopindolol). In contrast, the concentration-relaxation curve to CGP or cyanopindolol was significantly inhibited in endothelium-denuded rings or after L-NMMA treatment, suggesting that the atypical β-AR response was altered in SHR rats (P < 0.05 by ANOVA). Pertussis toxin treatment of SHR (10 µg kg^-1, I.P.) partly restored the endothelium-independent relaxation to CGP.

In conclusion, these results show that (1) atypical β-AR are functionally expressed in vascular smooth muscle of rat aorta, (2) they mediate a NO-independent vasorelaxation partly through a cAMP-dependent pathway, and (3) atypical β-AR relaxation is altered in hypertension and G_i protein pathway could be involved in this phenomenon.