Regulation of aortic smooth muscle relaxation in spontaneously hypertensive rats

Abstract

Hypertension may be caused by excessive vasoconstriction that can occur through a variety of dysfunctions in cellular mechanisms. Estrogen has been postulated to have protective properties against various cardiovascular pathologies and reported to play numerous direct and indirect roles within vascular smooth muscle. Therefore, the goals of this study were to examine two specific cellular mechanisms, the Rho-kinase pathway and the sarcoplasmic reticulum Ca²⁺-ATPase pump, that regulate smooth muscle activity in Spontaneously Hypertensive Rats (SHR). We also investigated whether ovariectomy caused differences in the effectiveness of these cellular pathways in aortic smooth muscle. The aortas from ovariectomized SHR were isolated, attached to force transducers, and placed in water jacketed chambers. All chambers were contracted with phenylephrine (PE) and treated with cyclopizonic acid (CPA), a sarcoplasmic reticulum Ca²⁺-ATPase pump inhibitor, or Y-27632, a Rho-kinase inhibitor. The tissues treated with CPA were relaxed with sodium nitroprusside (SNP), whereas Y-27632 was the relaxing agent in that group. As a result of our study, it was found that the cellular mechanisms that regulate contraction and relaxation in aortic smooth muscle are altered in SHR and were also significantly affected by ovariectomy. Our results also demonstrated that CPA and Y-27632 treatment significantly inhibited relaxation of aortic rings from ovariectomized spontaneous hypertensive rats. Together, these results suggest: (1) estrogen plays an important role in maintaining the function of the SR Ca²⁺-ATPase pump; and (2) estrogen has a facilitatory role in maintaining the integrity of the Ca²⁺-desensitization pathway (Rho-kinase -- myosin phosphatase interaction) in spontaneous hypertensive rats.