Differential regulation of G protein expression in rat hearts exposed to chronic hypoxia

Chronic hypoxia impairs adrenergic responsiveness. A modulation of G(s) and/or G(i) protein alpha-subunits may be associated with the downregulation of the beta-adrenergic receptors previously found in chronic hypoxia. G protein gene expression and protein level and function in rat hearts exposed to a 30-day hypobaric chronic hypoxia were compared with control rat hearts. No change was observed in G alpha(s) mRNA levels in either right or left ventricles. In right ventricles, mRNA levels of G alpha(i-2) increased by 40% (P < 0.05), but not in left ventricles. In both left and right ventricles, chronic hypoxia did not modify G alpha(i-2) and G alpha(s) protein amounts, but significantly decreased functional activity of G alpha(s). In conclusion, gene expression, protein levels of G alpha(s) and G alpha(i-2), and activity of G alpha(s) do not change in parallel fashion with chronic hypoxia. In chronic hypoxic right ventricles, although the mRNA level of G alpha(i-2) is increased, the protein level is unchanged. One potential mechanism of desensitization to catecholamines in chronic hypoxia appears to involve a decreased functional activity of G alpha(s) in spite of normal mRNA and protein levels.