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This Article Full Text Full Text (PDF) All Versions of this Article: 288/5/H2457    most recent 01090.2004v2 01090.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Schutzer, W. E. Articles by Mader, S. L. Search for Related Content PubMed PubMed Citation Articles by Schutzer, W. E. Articles by Mader, S. L.

Decline in caveolin-1 expression and scaffolding of G protein receptor kinase-2 with age in Fischer 344 aortic vascular smooth muscle

¹Portland Veterans Affairs Medical Center, Research Service, and ²Oregon Health and Science University, School of Medicine, Portland, Oregon

Submitted 2 October 2004 ; accepted in final form 16 December 2004

-Adrenergic receptor (-AR)-mediated vasorelaxation declines with age in humans and animal models. This is not caused by changes in expression of -AR, Gs, adenylyl cyclase, or protein kinase A but is associated with decreased cAMP production. Expression and activity of G protein receptor kinase-2 (GRK-2), which phosphorylates and desensitizes the -AR, increases with age in rat aortic tissue. Caveolin scaffolds the -AR, GRK, and other proteins within "signaling pockets" and inhibits GRK activity when bound. We questioned the effect of age on caveolin-1 expression and interaction between caveolin-1 and GRK-2 in vascular smooth muscle (VSM) isolated from 2-, 6-, 12-, and 24-mo-old male Fischer 344 rat aorta. Western blot analysis found expression of caveolin-1 declined with age (6-, 12- and 24-mo-old rat aortas express 92, 50, and 42% of 2-mo-old rat aortas, respectively). Results from density-buoyancy analysis showed a lower percentage of GRK in caveolin-1-specific fractions with age (6-, 12- and 24-mo-old rat aortas express 95, 56, and 12% of 2-mo-old rat aortas, respectively). Coimmunoprecipitation confirmed this finding; density of GRK in caveolin-1 immunoprecipitates was 97, 30, and 21% of 2-mo-old aortas compared with 6-, 12- and 24-mo-old animals, respectively. Immunohistocytochemistry and confocal microscopy confirmed that GRK-2 and caveolin-1 colocalize in VSM. These results suggest that in nonoverexpressed, intact tissue, the decline in -AR-mediated vasorelaxation may be caused by both a reduction in caveolin-1 expression and a reduction in binding of GRK-2 by caveolin-1. This could lead to an increase in the fraction of free GRK-2, which could phosphorylate and desensitize the -AR.

aging; aorta; -adrenergic; blood vessel; caveolae; hypertension

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