Beta-adrenergic responsiveness in cultured aorta smooth muscle cells. Effects of subculture and aging.
beta-Adrenoceptor-mediated vasorelaxation is diminished in vessels from a variety of aged species including humans. This phenomenon was studied for the first time in cultured aorta smooth muscle cells (ASMC) from young (4- to 6-month) and old (24- to 26-month) F-344 rats. Cyclic AMP (cAMP) accumulation was assessed following isoproterenol and forskolin stimulations in primary cultures and after 1-4 passages of aorta smooth muscle cells. Isoproterenol and forskolin increased cAMP accumulation 6- and 10-fold, respectively, in primary cultures from young rats. Isoproterenol stimulation was reduced markedly in passaged cells. Forskolin stimulation was unaffected, indicating passage-related phenotypic changes in receptor-mediated stimulation, but not in post-receptor adenylate cyclase activation. The response to isoproterenol was diminished in old animals, but that to forskolin was unaltered. Thus, cultured ASMC from F-344 rats are highly responsive to beta-adrenoceptor stimulation and demonstrate age-related changes, but undergo phenotypic modulation during passage.
Crass
M F
MF
Department of Physiology, Texas Tech University Health Sciences Center, Lubbock 79430.
Borst
S E
SE
Scarpace
P J
PJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging; D000818:Animals; D001013:Aorta, Thoracic; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008858:Microscopy, Phase-Contrast; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol