β2-adrenergic receptor gene delivery to the endothelium corrects impaired adrenergic vasorelaxation in hypertension

Guido Iaccarino, Ersilia Cipolletta, Antonia Fiorillo, Mario Annecchiarico, Michele Ciccarelli, Vincenzo Cimini, Walter J. Koch, Bruno Trimarco

Research output: Contribution to journalArticlepeer-review

Abstract

Background - Impaired β-adrenergic receptor (AR)-mediated vasorelaxation in hypertension plays a role in increased peripheral vascular resistance and blood pressure. Because the β2AR is the most abundant vascular AR subtype, we sought to enhance βAR vasorelaxation by overexpressing β2ARs via adenoviral-mediated gene transfer (ADβ2AR) 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 ADβ2AR 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 β2AR overexpression (2-fold) was studied in isolated organ baths. ADβ2AR carotid responses to α1AR and α2AR agonists were not affected, whereas responses to epinephrine were altered and βAR-mediated vasorelaxation was enhanced after β2AR overexpression. As expected, βAR-mediated vasodilatation in control carotids of SHR rats was significantly less than in similar control WKY carotid arteries. ADβ2AR treatment enhanced βAR vasorelaxation in SHR to levels similar to those seen in ADβ2AR WKY carotids. Conclusions - Our results demonstrate a critical role for the endothelium in βAR-mediated vasorelaxation and suggest that impaired βAR signaling may account for dysfunctional βAR vasorelaxation in hypertension rather than impaired endothelium-dependent nitric oxide metabolism.

Original languageEnglish
Pages (from-to)349-355
Number of pages7
JournalCirculation
Volume106
Issue number3
DOIs
Publication statusPublished - Jul 16 2002

Keywords

  • Endothelium
  • Gene therapy
  • Hypertension
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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