Oxygen and cyclic nucleotides in human umbilical artery.
In the human umbilical artery O2 has a direct contractile effect and is also required for induction of contraction by several other agents. Agonist that cause contraction (bradykinin, histamine, and serotonin) cause accumulation of guanosine 3':5'-monophosphate (cGMP) without altering adenosine 3':5'-monophosphate (cAMP). They appear to act through two different mechanisms: one Ca++-dependent, the other Ca++-inhibited. O2 increased the cGMP content of the artery in a Ca++-dependent manner without affecting the cAMP content. Inhibitors of oxidative phosphorylation (oligomycin and 2,4-dinitrophenol) did not diminish this effect of O2. O2 was required for demonstration of the Ca++-dependent accumulation of cGMP in response to bradykinin, histamine, and ionophore A23187. The effect of the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine on basal cGMP content and on the bradykinin-induced accumulation was also dependent on the presence of O2. Methylene blue and sodium ascorbate caused cGMP accumulation in O2-deprived arteries. Their effects were not diminished in Ca++-depleted arteries and, in fact, seemed to be inhibited when 2.7 mM Ca++ was present in the medium. The effects of these agents and of serotonin on cGMP, which were inhibited by Ca++, were also inhibited by O2. These non Ca++-, non O2-dependent agents (methylene blue, ascorbate, and serotonin) did not, however, permit demonstration of the effects of the Ca++- and O2-dependent agonists on O2-deprived arteries. It appears that there are in the umbilical artery (and probably in other tissues also) at least two separate mechanisms for control of cGMP synthesis that are influenced differently by Ca++- and O2-linked processes.
D000693:Anaerobiosis; D001205:Ascorbic Acid / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004140:Dinitrophenols / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008751:Methylene Blue / Q000494:pharmacology; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011247:Pregnancy; D011458:Prostaglandins E / Q000494:pharmacology; D014469:Umbilical Arteries / Q000187:drug effects / Q000378:metabolism*
D004140:Dinitrophenols; D009840:Oligomycins; D011458:Prostaglandins E; D000001:Calcimycin; D006632:Histamine; D000242:Cyclic AMP; D006152:Cyclic GMP; D001205:Ascorbic Acid; D001920:Bradykinin; D002118:Calcium; D008751:Methylene Blue