Background: Impaired beta-adrenergic receptor (AR)-mediated vasorelaxation in hypertension plays a role in increased peripheral vascular resistance and blood pressure. Because the beta(2)AR is the most abundant vascular AR subtype, we sought to enhance betaAR vasorelaxation by overexpressing beta(2)ARs via adenoviral-mediated gene transfer (ADbeta(2)AR) to the vascular endothelium of the carotid artery.
Methods and results: In normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, we exposed the right common carotid artery to ADbeta(2)AR in situ for 15 minutes by injection into the lumen while the blood flow was interrupted. Control carotids received an empty vector (ADempty). Three days later, transgene expression and selective endothelial localization were confirmed in infected vessels. Vasoregulation after beta(2)AR overexpression (2-fold) was studied in isolated organ baths. ADbeta(2)AR carotid responses to alpha(1)AR and alpha(2)AR agonists were not affected, whereas responses to epinephrine were altered and betaAR-mediated vasorelaxation was enhanced after beta(2)AR overexpression. As expected, betaAR-mediated vasodilatation in control carotids of SHR rats was significantly less than in similar control WKY carotid arteries. ADbeta(2)AR treatment enhanced betaAR vasorelaxation in SHR to levels similar to those seen in ADbeta(2)AR WKY carotids.
Conclusions: Our results demonstrate a critical role for the endothelium in betaAR-mediated vasorelaxation and suggest that impaired betaAR signaling may account for dysfunctional betaAR vasorelaxation in hypertension rather than impaired endothelium-dependent nitric oxide metabolism.