Short-term transdermal estradiol enhances nitric oxide synthase III and estrogen receptor mRNA expression in arteries of women with coronary artery disease.

OBJECTIVE: To analyze the short-term effects of estradiol (E2) on the expression of nitric oxide synthase (NOS III) and estrogen receptors (ER) alpha and beta. METHODS: We studied 20 post-menopausal women with coronary artery disease (CAD) undergoing CABG surgery with left internal mammary artery (LIMA) grafting. Ten women received treatment with transdermal E2 prior to surgery (48-72 h) and 10 did not. The distal segment of the LIMA was excised and processed to determine mRNA expression of NOS III and ER alpha and beta (RT-PCR). Expression of NOS III and ER alpha and beta was measured in arbitrary densitometric units (ADUs) relative to GPdH expression, constitutively expressed in human vessels. RESULTS: NOS III and ER alpha and beta mRNA expression was enhanced in women treated with E2 as compared to the control group (NOS III: 1.69+/-0.61 versus 1.14+/-0.48 ADUs, p=0.04; ER alpha: 6.52+/-6.80 versus 1.83+/-1.22 ADUs, p=0.04; ER beta: 4.20+/-3.42 versus 1.56+/-0.59 ADUs, p=0.03). ER alpha, but not ER beta expression, correlated with NOS III expression (r=0.70, p<0.001). CONCLUSIONS: After treatment with E2, NOS III, ER alpha, and ER beta mRNA expression was enhanced in arterial vessels of postmenopausal women with CAD. NOS III mRNA expression was only correlated to ER alpha expression, suggesting that NOS III activation could be more mediated by ER alpha.