Nebivolol induced concentration-dependent relaxation in rat thoracic aorta through both inhibition of alpha1-adrenoceptors (pA2 = 6.5) and activation of beta3-adrenoceptors.
Does nebivolol induce vasodilatation via alpha1 and beta3-adrenoceptors in rat thoracic aorta?
Nebivolol induces vasodilatation in rat aorta through both inhibition of alpha1-adrenoceptors and activation of beta3-adrenoceptors, involving the endothelium and NO pathway.
Effect estimate: pA2 6.5
Nebivolol, a selective beta-adrenoceptor (beta1-AR) antagonist, induces vasodilatation by an endothelium- and NO-cGMP-dependent pathway. However, the mechanisms involved in the vascular effect of nebivolol have not been established. Thus, we evaluated the role of alpha1 and beta3-ARs in nebivolol-induced vasodilatation. The responses to nebivolol were investigated in vitro in thoracic aortic rings isolated from male Sprague-Dawley rats. Nebivolol (0.1-10 microM) significantly shifted the concentration-response curve to phenylephrine, an alpha1-AR agonist, to the right in a concentration-dependent manner (pA2 = 6.5). Conversely, the concentration-response curve to endothelin 1 (ET1) was unaffected by nebivolol. In ET1-precontracted rings, nebivolol induced a concentration-dependent relaxation, which was unaffected by nadolol (a beta1/beta2-AR antagonist) but was significantly reduced by L-748,337 (a beta3-AR antagonist), endothelium removal or pretreatment with L-NMMA (an NOS inhibitor). Similar results were obtained with a beta3-AR agonist, SR 58611A. It was concluded that, in rat aorta, nebivolol-induced relaxation results from both inhibition of alpha1-ARs and activation of beta3-ARs. In addition, we confirmed that the endothelium and the NO pathway are involved in the vascular effect of nebivolol. The identification of these vascular targets of nebivolol indicate that it has therapeutic potential for the treatment of pathological conditions associated with an elevation of sympathetic tone, such as heart failure and hypertension.
Rozec et al. (Mon,) reported a other. Nebivolol was evaluated on Vasodilatation/relaxation of thoracic aortic rings (pA2 6.5). Nebivolol induced concentration-dependent relaxation in rat thoracic aorta through both inhibition of alpha1-adrenoceptors (pA2 = 6.5) and activation of beta3-adrenoceptors.