Giménez Jose, Garcia Paz M, Bonacasa Barbara, Carbonell Luis F, Quesada Tomas, Hernández Isabel
Departament of Physiology, Facultad de Medicina, Universidad de Murcia, Spain.
Exp Physiol. 2006 Jan;91(1):261-8. doi: 10.1113/expphysiol.2005.032060. Epub 2005 Nov 10.
We investigated the role of oestrogen in the function and structure of the microcirculation of female spontaneously hypertensive rats (SHRs), and evaluated the effect of 17beta-oestradiol on their cardiovascular response to pharmacological agents that block the formation of angiotensin II. Ten-week-old SHRs were randomly assigned to the following groups: intact, ovariectomized, and ovariectomized treated with 17beta-oestradiol (1.5 mg delivered over 60 days) and/or captopril (5 mg kg(-1) day(-1) for 8 weeks). Systolic blood pressure was determined from the time of ovariectomy up to 18 weeks of age, at which time endothelial function and microvascular density in skeletal muscle were evaluated. Both 17beta-oestradiol and captopril prevented development of hypertension in ovariectomized rats. Furthermore, coadministration of both drugs had a greater antihypertensive effect than either one alone. Acetylcholine-induced vasodilatation was impaired in ovariectomized SHRs, and the response was improved by treatment with 17beta-oestradiol and/or captopril. In addition, 17beta-oestradiol replacement in ovariectomized rats enhanced the effect of captopril on acetylcholine-induced vasodilatation. Ovariectomized rats also showed lower microvascular density than intact rats, an effect that was prevented by 17beta-oestradiol replacement or captopril treatment and, to a significantly larger extent, by coadministration of both. We concluded that both 17beta-oestradiol and captopril attenuated the development of hypertension and improved the impairment in microvascular density of ovariectomized SHRs. Moreover, when simultaneously administered, oestradiol and captopril had an additive effect on blood pressure and the microvasculature.
我们研究了雌激素在雌性自发性高血压大鼠(SHRs)微循环功能和结构中的作用,并评估了17β-雌二醇对其心血管系统对阻断血管紧张素II形成的药物反应的影响。将10周龄的SHRs随机分为以下几组:完整组、去卵巢组、去卵巢并用17β-雌二醇(60天内给予1.5mg)和/或卡托普利(5mg kg⁻¹ 每日,共8周)治疗组。从去卵巢时起至18周龄测定收缩压,此时评估骨骼肌的内皮功能和微血管密度。17β-雌二醇和卡托普利均可预防去卵巢大鼠高血压的发生。此外,两种药物联合使用的降压效果比单独使用任一药物更强。去卵巢的SHRs中乙酰胆碱诱导的血管舒张受损,而用17β-雌二醇和/或卡托普利治疗可改善这种反应。此外,去卵巢大鼠补充17β-雌二醇可增强卡托普利对乙酰胆碱诱导血管舒张的作用。去卵巢大鼠的微血管密度也低于完整大鼠,17β-雌二醇替代或卡托普利治疗可预防这种作用,而两者联合使用在更大程度上可预防。我们得出结论,17β-雌二醇和卡托普利均可减轻去卵巢SHRs高血压的发展并改善微血管密度的损害。此外,雌二醇和卡托普利同时给药时,对血压和微血管系统具有相加作用。