Progesterone and modulation of endothelium-dependent responses in canine coronary arteries

Am J Physiol. 1991 Oct;261(4 Pt 2):R1022-7. doi: 10.1152/ajpregu.1991.261.4.R1022.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / pharmacology
  • Adenosine Diphosphate / pharmacology
  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Arteries
  • Azepines / pharmacology
  • Coronary Vessels / drug effects
  • Coronary Vessels / physiology*
  • Dogs
  • Endothelium, Vascular / physiology*
  • Estrogens / blood
  • Estrogens / pharmacology
  • Female
  • Progesterone / pharmacology*
  • Vasodilation / drug effects

Substances

  • Adrenergic alpha-Agonists
  • Azepines
  • Estrogens
  • Progesterone
  • Adenosine Diphosphate
  • talipexole
  • Acetylcholine