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) Ca²⁺ 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 (φ) 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 φ was completely restored in 8.2 ± 2.6 min (n = 6). Similarly, cell impermeant albumin-conjugated progesterone, but not albumin-conjugated 17β-estradiol, decreased 5-HT+U stimulated VMC Ca²⁺ 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.