Effects of oestrogen treatment and angiotensin‐converting enzyme inhibition on the microvasculature of ovariectomized spontaneously hypertensive rats

Abstract

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 17β-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 17β-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 17β-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 17β-oestradiol and/or captopril. In addition, 17β-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 17β-oestradiol replacement or captopril treatment and, to a significantly larger extent, by coadministration of both. We concluded that both 17β-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.

Nicotine and vascular endothelial dysfunction in female ovariectomized rats: role of estrogen replacement therapy

“…Estrogens are thought to contribute to the maintenance of normal endothelial function. The vasculoprotective effects of estrogen are mediated through genomic and non‐genomic mechanisms, and may be attributed to their ability to increase the availability of NO through activation of eNOS [20] . This contention is supported by the results obtained in this study that ERT increases the plasma concentration of NO and aortic eNOS expression and hence cGMP production.…”

“…Vasoconstrictor prostanoids, such as thromboxane A2 (TXA2), have also been implicated in the pathophysiology of vascular dysfunction during estrogen withdrawal and aging [19] . Previous studies suggest that the loss of endogenous estrogens leads to reduced bioavailability of endothelium‐derived NO and impaired endothelial function [20] . The increased NO production due to estrogen replacement therapy (ERT) might explain why it has beneficial effects on endothelial function.…”

“…[19] Previous studies suggest that the loss of endogenous estrogens leads to reduced bioavailability of endotheliumderived NO and impaired endothelial function. [20] The increased NO production due to estrogen replacement therapy (ERT) might explain why it has beneficial effects on endothelial function. Therefore, this study was undertaken to investigate the effect of ERT on ovariectomynicotine-induced VED in female rats exposed to nicotine at a lower dose level, similar to that received by passive smokers.…”

STIM1/Orai1 contributes to sex differences in vascular responses to calcium in spontaneously hypertensive rats

“…In accordance with other studies [39, 40], we observed that ovariectomy increased systolic blood pressure in female rats, which reveal the protective effect of sex-hormones in the blood pressure control. It is known that estrogen has protective vascular effects.…”

The contributions of muscarinic receptors and changes in plasma aldosterone levels to the anti-hypertensive effect of Tulbaghia violacea

“…Muscarine reduces BP, while atropine has various effects on BP, from increases [36-38], to no effect in normotensive Wistar Kyoto (WKY) rats and SHR [39,40], and decreases at doses of 5–50 mg/kg intravenously infused to conscious un-anaesthetized WKY rats and hypertensive rats (SHR, and Sprague–Dawley rats made hypertensive by subcutaneous implantation of deoxycorticosterone acetate) [41-43]. Atropine has also been reported to produce vasodilation [28,44]. …”