Beta-adrenergic responsiveness in cultured vascular smooth muscle cells and fibroblasts: effect of age.
beta-Adrenergic agonists stimulate cyclic 3',5'-adenosine monophosphate (cAMP) accumulation and relaxation in vascular smooth muscle; both of these responses decline in rat aorta with increasing age. To ascertain whether the deficit in beta-receptor stimulated cAMP accumulation persists in isolated aortic smooth muscle cells, the effect of isoproterenol on cAMP accumulation was measured in cultured vascular smooth muscle cells (VSMC) and vascular fibroblasts taken from young (4-6 weeks) and older (8-12 months) Fischer 344 male rats. Immunofluorescent staining confirmed the identity of VSMC as distinct from fibroblasts. Isoproterenol stimulated cAMP accumulation in a time- and concentration-dependent manner in both cell types; maximal cAMP accumulation induced by beta-adrenergic stimulation in cultured cells was much higher than those seen in the intact aorta. While there was a blunting of cAMP response to isoproterenol in fibroblasts cultured from the older rats, the response in VSMC cultured from the older rats was actually increased compared to the VSMC cultured from the younger rats. In contrast, activation of cAMP accumulation in the cultured cells by forskolin was similar in cells from older and young animals. The results suggest that the blunting in isoproterenol-stimulated cAMP accumulation found in aortas from older animals is not seen in VSMC cultured from these animals; whether this change in the culture reflects removal of some extrinsic factor in the older rats or is a consequence of intrinsic changes in the cells in culture requires further investigation.
Chin
J H
JH
Department of Medicine, Stanford University School of Medicine, Palo Alto, California 94304.
Hoffman
B B
BB
D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000166:cytology; D002478:Cells, Cultured; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D007545:Isoproterenol; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012044:Regression Analysis
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000242:Cyclic AMP; D007545:Isoproterenol