A NOVEL, NONGENOMIC ACTION OF ESTROGEN ON THE CARDIOVASCULAR-SYSTEM

To examine the time course and mechanisms of action of single doses of estrogen on the skin microvasculature, two double-blind placebo-contr olled cross-over studies were conducted in healthy young men using the noninvasive technique of laser Doppler velocimetry with iontophoretic application of vasodilator substances. Estradiol (2 mg sublingually) produced a significant increase in the response to the endothelial vas odilator acetylcholine (ACh) after 15 min, but not after 20 or 30 min. The mean plasma estradiol concentration increased from 89.4 +/- 9 pmo l/L at baseline to 486.6 +/- 218 pmol/L at 15 min. An iv bolus of 25 m g conjugated equine estrogens produced significant increases in the re sponses to ACh at 15 and 20 min but not at 30 min. There was no change in responses to the nonendothelial vasodilators sodium nitroprusside or nicotine, and administration of placebo produced no change in ACh r esponses at any time point. These experiments show that, at plasma est radiol concentrations within the physiological range for premenopausal women, estrogens act directly on the cutaneous microvasculature throu gh a rapid onset, rapid offset, nongenomic mechanism that is specific to the endothelium; in addition, it supports the view that estrogens c an act on the male cardiovascular system in a manner that is potential ly clinically beneficial.