HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Schutzer, W. E. Articles by Mader, S. L. PubMed PubMed Citation Articles by Schutzer, W. E. Articles by Mader, S. L.

Effect of Age on Vascular ß₂-Adrenergic Receptor Desensitization Is Not Mediated by the Receptor Coupling to Gi Proteins

¹ Portland VA Medical Center, Research Service, Oregon.
² Oregon Health & Science University, School of Medicine, Portland.

Address correspondence to Scott L. Mader, MD, Portland VA Medical Center, Research Service–R&D 26, 3710 SW US Veterans Hospital Rd., Portland, OR 97201. E-mail: scott.mader{at}med.va.gov

Beta-adrenergic receptor (ß-AR)-mediated vasorelaxation declines with age. In the vasculature, ß₂-AR undergoes protein kinase A-mediated desensitization that causes a switch in the G protein coupled to ß₂-AR; Gi links instead of Gs. We exposed Fischer 344 rat aortae of increasing age to a desensitizing dose of isoproterenol, and determined its effect on ß₂-AR-mediated vasorelaxation. Desensitization decreased ß₂-AR-mediated vasorelaxation in young aortae only. Subsequently, we used pertussis toxin to block Gi to determine whether changes in ß₂-AR/G protein coupling occurred. Gi inhibition did not reverse desensitization or the age-related change, but there appears to be a population of ß₂-AR linked to Gi, as pertussis toxin treatment improved ß₂-AR-mediated vasorelaxation in aortae from animals of all ages. These findings suggest aortic ß₂-AR in older animals may be maximally desensitized, which would explain impaired vasorelaxation. Our results also imply that protein kinase A-mediated ß₂-AR desensitization may not be responsible for the age-related decline.