Effects of treatment with 17β-estradiol on the hypercholesterolemic rabbit middle cerebral artery

Objective: The effects of acute and long-term treatment with 17 beta-estradiol on the vasomotor responses of rabbit middle cerebral artery (RMCA) were investigated. Methods: For 8 weeks, male rabbits consumed standard chow (control group), standard chow + 1% cholesterol (cholesterol group) or 1% cholesterol chow + 17 beta-estradiol (i.m. injection 700 mu g per week) (estradiol group). The RMCA was precontracted with high K+ solution and exposed to agonists. Results: Acute exposure to 17 beta-estradiol strongly induced relaxation of the RMCA isolated from either control or cholesterol groups. This effect was endothelium independent. Incubation with 17 beta-estradiol shifted the calcium contraction curve to the right. High cholesterol diet impaired the relaxation induced by acetylcholine and did not alter relaxation to sodium nitroprusside or to papaverine. Chronic treatment with 17 beta-estradiol restored this impaired relaxation to acetylcholine. This protective effect of estradiol was significantly reduced in the presence of N-omega nitro-L-arginine methyl eater, a constitutive nitric oxide-synthase inhibitor and was not modified in the presence of aminoguanidine, an inducible nitric oxide-synthase inhibitor. Neither tetrabutylammonium, a blocker of calcium-activated Kt channels, nor glibenclamide, a blocker of ATP-sensitive K+ channels, affected concentration-response to acetylcholine in the RMCA of the estradiol group, whereas 4-aminopyridine, a blocker of voltage-dependent K+ channels strongly inhibited this relaxation. Conclusions: These results suggest that acute effects of 17 beta-estradiol in the RMCA is mediated through blockade of calcium entry into vascular smooth muscle cells. while chronic treatment with this hormone seems to be mediated by release of nitric oxide which activates voltage-dependent potassium channels. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.