Nongenomic vasodilator action of progesterone on primate coronary arteries

• Published in: Journal of applied physiology (1985) 2002-02, Vol.92 (2), p.701-708
• Main Authors: Minshall, Richard D, Pavcnik, Dusan, Browne, David L, Hermsmeyer, Kent
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Biological and medical sciences; Calcium - metabolism; Coronary Vasospasm - chemically induced; Coronary Vasospasm - physiopathology; Coronary vessels; Coronary Vessels - drug effects; Coronary Vessels - physiopathology; Drug Combinations; Estradiol - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Gynecology; Heart; Hormones; Injections, Intra-Arterial; Macaca mulatta; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Ovariectomy; Progesterone - administration & dosage; Progesterone - pharmacology; Serotonin; Serum Albumin, Bovine - pharmacology; Ultrasonic imaging; Vasoconstriction - drug effects; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents - pharmacology; Vertebrates: cardiovascular system
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00689.2001

1  Oregon Regional Primate Research Center, Beaverton 97006; and 2  The Dotter Interventional Institute, Oregon Health Sciences University, and 3  Dimera LLC, Portland, Oregon 97210 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 µM serotonin and 1 µM U-46619 (5-HT+U; 1 ml/30 s), resulted in a decrease in CA diameter ( ) 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  was completely restored in 8.2   ± 2.6 min ( n  = 6). Similarly, cell impermeant albumin-conjugated progesterone, but not albumin-conjugated 17 -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. vasospasm; angiography; ovarian steroids; nongenomic effects; low-dose progesterone; vascular muscle cell