Progesterone and modulation of endothelium-dependent responses in canine coronary arteries.
Chronic treatment with estrogens enhances some endothelium-dependent relaxations. Whether or not progesterone would exert a similar effect is unknown. Experiments were designed to determine the effect of chronic treatment with progesterone on endothelium-dependent responses. Adult female dogs were ovariectomized and pellets containing carrier substance, estrogen, progesterone, or estrogen plus progesterone were implanted subcutaneously. After 14-21 days coronary arteries were removed, cut into rings, and suspended for the measurement of isometric force in organ chambers in the presence of indomethacin. Endothelium-dependent relaxations to ADP, bradykinin, or the calcium ionophore did not differ among groups. However, relaxations to acetylcholine and to the alpha 2-adrenergic agonist BHT-920 were greater in the estrogen-treated group than in the estrogen plus progesterone-treated group. In rings without endothelium, relaxations to nitric oxide and isoproterenol did not differ among groups. However, relaxations of the smooth muscle to ADP were greater in the progesterone-treated group than in the progesterone plus estrogen group. These results suggest that progesterone alone minimally affects endothelium-dependent responses. However, progesterone seems to antagonize the stimulatory effects of estrogen on two endothelium-dependent responses that are associated with pertussis toxin-sensitive guanine nucleotide regulatory proteins and the production of nitric oxide. These studies suggest that a specific receptor/second messenger system can be modulated by female reproductive steroid hormones.
Department of Physiology and Biophysics, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
V M
VM
Miller
P M
PM
Vanhoutte
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D001381:Azepines / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D004967:Estrogens / Q000097:blood / Q000494:pharmacology; D005260:Female; D011374:Progesterone / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D004967:Estrogens; D011374:Progesterone; D000244:Adenosine Diphosphate; C024763:talipexole; D000109:Acetylcholine