Chronic cyclic strain reduces adenylate cyclase activity and stimulatory G protein subunit levels in coronary smooth muscle cells.
Previous studies from this laboratory have demonstrated that acute cyclic strain causes a reduction in adenylate cyclase activity in cultured coronary vascular smooth muscle cells. The objective of this study was to test the hypothesis that chronic cyclic strain of coronary vascular smooth muscle cells also causes inhibition of adenylate cyclase activity and that this may be related to changes in G protein steady-state levels. Cultured smooth muscle cells obtained from porcine coronary artery were subjected to 24 h of cyclic strain of 20 kPa (24% maximum strain) at 60 cycles/min. Unstretched cells served as controls. Basal, Gpp(NH)p, and forskolin plus Mn(2+)-stimulated adenylate cyclase activities were inhibited significantly in stretched versus unstretched vascular smooth muscle cells. The reduction in adenylate cyclase activity observed after 24 h of cyclic strain was associated with a significant (P < 0.05 vs controls) reduction in steady-state levels of Gs alpha 45, whereas Gi alpha 1,2 and G beta levels remained unchanged. The data support the hypothesis that adenylate cyclase activity and G protein steady-state levels in coronary smooth muscle are sensitive to chronic cyclic strain. It suggests that the G protein adenylate cyclase effector pathway may play an important role in the subacute adaptation of the coronary circulation to changes in intravascular pressure.
Wiersbitzky
M
M
Department of Medicine, Rhode Island Hospital, Brown University, Providence 02903.
Mills
I
I
Sumpio
B E
BE
Gewirtz
H
H
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D010507:Periodicity; D013314:Stress, Mechanical; D013552:Swine
D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases