Altered myocardial Gs protein and adenylyl cyclase signaling in rats exposed to chronic hypoxia and normoxic recovery.
The present work has analyzed the consequences of chronic intermittent high-altitude hypoxia for functioning of the G protein-mediated adenylyl cyclase (AC) signaling system in the right (RV) and left ventricular (LV) myocardium in rats. Adaptation to hypoxia did not appreciably affect the number of beta-adrenoceptors and the content of predominantly membrane-bound alpha-subunit (G(s)alpha) of the stimulatory G protein, but it raised the amount of cytosolic G(s)alpha in RV. The levels of myocardial inhibitory Galpha protein were not altered. Activity of AC stimulated by GTP, fluoride, forskolin, or isoprotertenol was reduced by approximately 50% in RV from chronically hypoxic rats, and a weaker depression was also found in LV. In addition, hypoxia significantly diminished a functional activity of membrane-bound G(s)alpha in both RV and LV. The RV baseline contractile function was markedly increased in chronically hypoxic animals, and its sensitivity to beta-adrenergic stimulation was decreased. Animals recovering from hypoxia for 5 wk still exhibited markedly elevated levels of cytosolic G(s)alpha and significantly lower activity of AC in RV than did age-matched controls, but contractile responsiveness to beta-agonists was normal.
Hrbasová
Markéta
M
Faculty of Natural Sciences, Department of Physiology and Developmental Biology, Charles University, Vinicna 7, Prague 2, Czech Republic.
Novotny
Jiri
J
Hejnová
Lucie
L
Kolár
Frantisek
F
Neckár
Jan
J
Svoboda
Petr
P
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001274:Atmospheric Pressure; D001835:Body Weight; D002316:Cardiotonic Agents / Q000494:pharmacology; D002908:Chronic Disease; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction; D016278:Ventricular Function, Right
D002316:Cardiotonic Agents; D020033:Protein Isoforms; D011943:Receptors, Adrenergic, beta; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; D007545:Isoproterenol