Nongenomic action of progesterone in rat aorta: role of nitric oxide and prostaglandins.
The mechanism of action of progesterone (Pg) on rat vascular tissue was investigated. We obtained evidence that 10-nM Pg inhibited platelet aggregation at 1-5 min. Previously, we reported that nitric oxide (NO) mediated this antiaggregatory effect. Rat aortic strips (RAS) NO synthase (NOS) activity in response to "in vitro" treatment with other sex steroids hormones was measured. The stimulatory action of Pg on NO production was specific for ovarian hormones and depends on sex. The effect was nongenomic since cycloheximide did not suppress the increment in NO induced by Pg. Finally, we demonstrated that Pg (5 min) increased prostacyclin release (42-182% above control) in a dose-dependent manner (1-100 nM). Indeed, indomethacin (10 microM) completely suppressed the increment in citrulline levels induced by the hormone. These results suggest that Pg exerts a direct nongenomic action on rat aortic metabolism, which involves NOS and cyclooxygenase (COX) activation and a cross-talk between NO- and prostacyclin (PGI(2))-dependent pathways.
Selles
Juana
J
Cátedra de Analisis Clínicos II, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000ICN, Bahia Blanca, Argentina.
Polini
Nélida
N
Alvarez
Cristina
C
Massheimer
Virginia
V
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D046508:Culture Techniques; D011464:Epoprostenol / Q000502:physiology*; D005260:Female; D016678:Genome; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
D012739:Gonadal Steroid Hormones; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D011374:Progesterone; D001120:Arginine; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases