This Article Full Text Full Text (PDF) Services Download to citation manager PubMed PubMed Citation

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.