Estrogen alters relative contributions of nitric oxide and cyclooxygenase products to endothelium-dependent vasodilation

The purpose of this study was to determine the effects of in vivo estrogen manipulations on mechanisms of endothelium-dependent vasodilation. Ovary-in tact, ovariectomized (OVX), or OVX with estrogen replacement (OVX + E-2) fe male Sprague-Dawley rats were studied (n = 8). Mesenteric arteries (similar to 300 mu m) were isolated, cannulated, and pressurized to 60 mm Hg in an arteriograph containing bicarbonate buffer and vessel diameter was monitore d. Concentration-response curves to the endothelium-dependent histamine H-1 agonist 2-thiazolylethylamine (2-TEA; 1 nM-100 mu M) and to acetylcholine (1 nM-10 mu M) were performed in preconstricted arteries. The effect of N o mega-nitro-L-arginine (LNA; 100 mu M) or LNA + indomethacin (INDO) (10 mu M ) on agonist-induced vasodilation was determined. There was no difference b etween treatment groups in the sensitivity of mesenteric arteries to 2-TEA or acetylcholine. LNA produced a significant decrease in sensitivity to 2-T EA in arteries from ovary-intact and OVX + E-2 rats but not in those from O VX rats. The addition of INDO produced a small additional decrease in sensi tivity to 2-TEA in arteries from ovary-intact rats, a significant decrease in OVX, and no shift in OVX 1 E-2. LNA 1 INDO produced a similar degree of inhibition of the 2-TEA response in the three treatment groups. In contrast , when acetylcholine was used, the decrease in sensitivity produced by LNA or LNA + INDO was similar in the three rat groups. We conclude that estroge n increases the nitric oxide component of endothelium-dependent dilation an d decreases the cyclooxygenase component. These effects of estrogen appear to be agonist-specific. Our findings suggest that estrogen modulates cross talk between the nitric oxide synthase and cyclooxygenase pathways of vasod ilation.