The nongenomic protective effects of estrogen on the male cardiovascular system: clinical and therapeutic implications in aging men.
Although the preponderance of studies investigating the effects of estrogen on vasomotor tone and function have focused on women, a number of recent studies have intriguingly shown that estrogen's rapid vasodilatory properties is also preserved in men. Unlike classical steroid transcription mediated pathways, estrogen's acute vasodilatory effect is mediated by calcium dependent cell surface estrogen receptors that stimulate constitutive endothelial nitric oxide synthase (eNOS) activity. The transient release of eNOS derived nitric oxide exerts profound physiological effects on the vasculature exerting a state of cellular inhibition (i.e. vasodilation). Thus, the partial or complete attenuation of this rapid signaling system can promote endothelial dysfunction, an early pathophysiological event in atherosclerotic development. Consequently, human males experiencing age-related declines in testosterone and aromatase derived estradiol plasma levels may lose a vital cardioprotective mechanism that preserves proper endothelial function. Therapeutic strategies to preserve basal nitric oxide levels through the maintenance of normal physiological estradiol levels may confer cardiovascular benefits to aging males.
Cho
John J
JJ
Neuroscience Research Institute State University of New York Old Westbury, Old Westbury, NY 11568-0210, USA.
Cadet
Patrick
P
Salamon
Elliott
E
Mantione
Kirk
K
Stefano
George B
GB
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002320:Cardiovascular Physiological Phenomena; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology; D004967:Estrogens / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D015398:Signal Transduction; D013739:Testosterone / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D004967:Estrogens; D009569:Nitric Oxide; D013739:Testosterone; D004958:Estradiol; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III