DIFFERENTIAL REGULATION OF G-PROTEIN EXPRESSION IN RAT HEARTS EXPOSEDTO CHRONIC HYPOXIA

Chronic hypoxia impairs adrenergic responsiveness. A modulation of G(s ) and/or G(i) protein alpha-subunits may be associated with the downre gulation of the beta-adrenergic receptors previously found in chronic hypoxia. G protein gene expression and protein level and function in r at hearts exposed to a 30-day hypobaric chronic hypoxia were compared with control rat hearts. No change was observed in G alpha(s) mRNA lev els in either right or left ventricles. In right ventricles, mRNA leve ls of G alpha(i-2) increased by 40% (P < 0.05), but not in left ventri cles. In both left and right ventricles, chronic hypoxia did not modif y G alpha(i-2) and G alpha(s) protein amounts, but significantly decre ased 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 alp ha(s) do not change in parallel fashion with chronic hypoxia. In chron ic hypoxic right ventricles, although the mRNA level of G alpha(i-2) i s increased, the protein level is unchanged. One potential mechanism o f desensitization to catecholamines in chronic hypoxia appears to invo lve a decreased functional activity of G alpha(s) in spite of normal m RNA and protein levels.