nitroarginine and 2-(2-aminoethyl)thiazole

The purpose of this study was to determine the effects of in vivo estrogen manipulations on mechanisms of endothelium-dependent vasodilation. Ovary-intact, ovariectomized (OVX), or OVX with estrogen replacement (OVX + E(2)) female Sprague-Dawley rats were studied (n = 8). Mesenteric arteries (approximately 300 microm) were isolated, cannulated, and pressurized to 60 mm Hg in an arteriograph containing bicarbonate buffer and vessel diameter was monitored. Concentration-response curves to the endothelium-dependent histamine H(1) agonist 2-thiazolylethylamine (2-TEA; 1 nM-100 microM) and to acetylcholine (1 nM-10 microM) were performed in preconstricted arteries. The effect of Nomega-nitro-L-arginine (LNA; 100 microM) or LNA + indomethacin (INDO) (10 microM) on agonist-induced vasodilation was determined. There was no difference between treatment groups in the sensitivity of mesenteric arteries to 2-TEA or acetylcholine. LNA produced a significant decrease in sensitivity to 2-TEA in arteries from ovary-intact and OVX + E(2) rats but not in those from OVX rats. The addition of INDO produced a small additional decrease in sensitivity to 2-TEA in arteries from ovary-intact rats, a significant decrease in OVX, and no shift in OVX + E(2). LNA + 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 estrogen increases the nitric oxide component of endothelium-dependent dilation and 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 vasodilation.

Topics: Acetylcholine; Animals; Dose-Response Relationship, Drug; Drug Interactions; Estrogens; Female; In Vitro Techniques; Indomethacin; Mesenteric Arteries; Nitric Oxide; Nitroarginine; Ovariectomy; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Thiazoles