Altered myocardial G_sprotein and adenylyl cyclase signaling in rats exposed to chronic hypoxia and normoxic recovery

Abstract

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.

Effect of sustained hypobaric hypoxia during maturation and aging on rat myocardium. I. Mechanical activity

“…Adaptation of adult rats to intermittent high-altitude hypoxia for 5 wk increased RV contractile function, determined as developed pressure, maximal rate of pressure development, and maximal rate of pressure fall (27). The increase of the same parameters in the LV as reported in this study suggests that they are caused by adaptation to hypoxia rather than by RV hypertrophy.…”

Chronic intermittent hypobaric hypoxia decreases β-adrenoceptor activity in right ventricular papillary muscle

“…On the other hand, there was a report that chronic hypoxia did not appreciably affect the content of the stimulatory G protein (9). In the present study, we found that the biologically active isoform, G s ␣ (45 kDa), was reduced in myocardium in CIHH rats, suggesting that the reduced activity of ␤-adrenergic receptor was related with the reduction of G s ␣ protein.…”

Chronic prenatal hypoxia sensitizes β-adrenoceptors in the embryonic heart but causes postnatal desensitization

“…The hypoxic decrease of ␤-AR density and function in the adult animal is reversible with normoxic recovery (11). However, exposure of the 1-day-old neonate to hypoxia over 10 days and subsequent normoxic recovery for 11 wk renders an adult animal that has a maintained receptor density but a lowered sensitivity to ␤-AR agonist stimulation (25).…”