Nongenomic vasodilator action of progesterone on primate coronary arteries.
In the present investigation, we test the hypothesis that progesterone can rapidly relax, via a nongenomic mechanism, persistent flow occluding, agonist-activated coronary artery (CA) vasospasm, and hyperreactive vascular muscle cell (VMC) Ca(2+) responses in ovariectomized rhesus monkeys. CA vasospasm, induced by injection of 100 microM serotonin and 1 microM U-46619 (5-HT+U; 1 ml/30 s), resulted in a decrease in CA diameter (phi) from 1.8 +/- 0.2 to 0.3 +/- 0.1 mm at the site of focal constriction. Injection of 100 ng progesterone into the CA significantly relieved the severe vasoconstriction (1.3 +/- 0.2 mm) and reestablished distal flow in 3 min; the preconstriction phi was completely restored in 8.2 +/- 2.6 min (n = 6). Similarly, cell impermeant albumin-conjugated progesterone, but not albumin-conjugated 17 beta-estradiol, decreased 5-HT+U stimulated VMC Ca(2+) responses (250 +/- 34% of basal 30 min after stimulation) back to the prestimulation level (113 +/- 17% of basal) in 25 min (half time = 7 min). The presence of a rapid vasodilator action of progesterone in the primate CA and isolated VMC suggests its benefits in hormone replacement therapy may also include nongenomic vascular relaxant actions.
Minshall
Richard D
RD
Oregon Regional Primate Research Center, Beaverton 97006, Oregon, USA.
Pavcnik
Dusan
D
Browne
David L
DL
Hermsmeyer
Kent
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003329:Coronary Vasospasm / Q000139:chemically induced / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007269:Injections, Intra-Arterial; D008253:Macaca mulatta; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*; D012701:Serotonin; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
D004338:Drug Combinations; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D012710:Serum Albumin, Bovine; D012701:Serotonin; D011374:Progesterone; D004958:Estradiol; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002118:Calcium