Published online before print June 17, 2002, doi: 10.1161/01.CIR.0000022690.55143.56
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(Circulation. 2002;106:349.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
ß2-Adrenergic Receptor Gene Delivery to the Endothelium Corrects Impaired Adrenergic Vasorelaxation in Hypertension
From the Department of Clinical Medicine, Cardiovascular and Immunological Sciences (G.I., E.C., A.F., M.A., M.C., B.T.), and Biomorphological and Functional Sciences (V.C.), Federico II University, Naples, Italy; and the Department of Surgery (W.J.K.), Duke University Medical Center, Durham, NC.
Correspondence to Guido Iaccarino, MD, PhD, Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Federico II University, Via Pansini 5, 80131 Naples, Italy. E-mail guiaccar{at}unina.it
Background— Impaired ß-adrenergic receptor (AR)–mediated vasorelaxation in hypertension plays a role in increased peripheral vascular resistance and blood pressure. Because the ß2AR is the most abundant vascular AR subtype, we sought to enhance ßAR vasorelaxation by overexpressing ß2ARs via adenoviral-mediated gene transfer (ADß2AR) 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 ADß2AR 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 ß2AR overexpression (2-fold) was studied in isolated organ baths. ADß2AR carotid responses to 
1AR and 2AR agonists were not affected, whereas responses to epinephrine were altered and ßAR-mediated vasorelaxation was enhanced after ß2AR overexpression. As expected, ßAR-mediated vasodilatation in control carotids of SHR rats was significantly less than in similar control WKY carotid arteries. ADß2AR treatment enhanced ßAR vasorelaxation in SHR to levels similar to those seen in ADß2AR WKY carotids.
Conclusions— Our results demonstrate a critical role for the endothelium in ßAR-mediated vasorelaxation and suggest that impaired ßAR signaling may account for dysfunctional ßAR vasorelaxation in hypertension rather than impaired endothelium-dependent nitric oxide metabolism.
Key Words: endothelium • gene therapy • hypertension • signal transduction
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