Modulation of coronary vascular resistance in female rabbits by estrogen and progesterone.
OBJECTIVE
To study the roles of estradiol and various progestins on the regulation of coronary flow in female rabbits.


METHODS
Ovariectomized adult female rabbits were treated with estradiol, with progesterone (or one of the following synthetic progestins: megace, norethindrone, or medroxyprogesterone acetate), or with both an estradiol and a progestin. Hearts were isolated and perfused at constant pressure by a modified Langendorff technique. Changes in coronary flow were determined at baseline and in response to direct infusion into the coronary circulation of NG-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide (NO) synthase.


RESULTS
Coronary flow rates were 40-50% greater in hearts of animals treated with estradiol than in control hearts of animals not treated with the hormone. Treatment of the animals with progestin alone had little effect on coronary flow. However, when administered with estradiol, it abrogated the estradiol-related increase in coronary flow. The increments in coronary flow evoked by estradiol were virtually abolished by L-NNA, an inhibitor of NO synthase. In hearts of animals treated with estradiol plus progesterone, L-NNA had no additional inhibitory effect on coronary flow to that of progesterone.


CONCLUSIONS
Estradiol decreases coronary vascular resistance (CVR) and hence increases coronary flow. Progestins attenuate this effect of estradiol.
Gorodeski
G I
GI
Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Yang
T
T
Levy
M N
MN
Goldfarb
J
J
Utian
W H
WH
D000818:Animals; D001783:Blood Flow Velocity; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D019290:Megestrol Acetate / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009640:Norethindrone / Q000494:pharmacology; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects*
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D011374:Progesterone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D019001:Nitric Oxide Synthase; D009640:Norethindrone; D019290:Megestrol Acetate