Effects of prolonged hypoxia on adenylate cyclase activity and beta-adrenergic receptors in pulmonary and systemic arteries of the rat.
Prolonged hypoxia causes pulmonary hypertension but no change in systemic vasomotor tone. In an effort to define the mechanisms involved, we determined the effects of 3 and 7 days of hypoxia on adenylate cyclase activity and beta-adrenergic receptor binding characteristics in pulmonary and systemic arteries in an adult rat model of hypoxic pulmonary vasoconstriction produced by hypobaria. Basal and stimulated adenylate cyclase activity were measured in crude membrane preparations by radioimmunoassay for cyclic AMP. Basal enzyme activity in pulmonary arteries did not change with hypoxia, whereas in systemic arteries it increased 3.5- and 5.3-fold following 3 and 7 days of hypoxia, respectively. GTP-stimulated activity in pulmonary arteries also did not change, but in systemic arteries it increased 7.1- and 5.5-fold. Isoproterenol-stimulated activity in pulmonary arteries was decreased to 49% of control-stimulated activity following 3 days but was similar to control-stimulated activity after 7 days of hypoxia; in systemic arteries it increased 5.6- and 4.6-fold. Sodium fluoride-stimulated activity in pulmonary arteries was unchanged, whereas in systemic arteries it increased 3.8- and 5.3-fold. In contrast, forskolin-stimulated activity, which also was not altered in pulmonary arteries, was increased by only 85% and 71% in systemic arteries. beta-Adrenergic receptors were studied with [125I]iodocyanopindolol. Seven days of hypoxia decreased receptor density by 37% and 57% in the pulmonary and systemic arteries, respectively. Receptor affinity for agonists was not altered. Thus, despite downregulation of beta-adrenergic receptors in both artery types, prolonged hypoxia has no sustained effect on adenylate cyclase activity in pulmonary arteries, whereas enzyme activity in systemic arteries is markedly increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Shaul
P W
PW
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
Muntz
K H
KH
DeBeltz
D
D
Buja
L M
LM
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D011506:Proteins / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013997:Time Factors
D011506:Proteins; D011943:Receptors, Adrenergic, beta; D004247:DNA; D000262:Adenylyl Cyclases