Estrogen Protects Vasomotor Functions in Rats During Catecholamine Stress

Abstract

The incidence of dysfunctional vasomotor diseases has mostly occurred in postmenopausal women but not in premenopausal women. Hence, this study sought to investigate the impact of estrogen deficiency during catecholamine stress on vasomotor function. Also, attempts were made to utilize estrogen replacement therapy to mitigate the adverse effects (pathological remodeling) of stress on the aortic vessels to preserve vasomotor functions. To do this, female Sprague-Dawley (SD) rats were ovariectomized (OVX) along with sham operations (Sham). Day 14 after OVX operation, 17-estradiol (E2) was subcutaneously implanted (OVX+E2). Day 35 after operation, stress was induced by isoproterenol (ISO) subcutaneous injections. Clinically relevant blood pressure indexes (systolic, diastolic, and mean atrial blood pressures) were assessed in the rats. Aortic vascular ring tensions were assessed in vitro to ascertain the impact of E2 on their vasomotor function. Aortic vascular rings (AVRs) from OVX+ISO exhibited a significant increase in contractility in response to phenylephrine than AVRs isolated from Sham+ISO rats. Also, sera levels of nitric oxide (NO) and endothelin-1 (ET-1) and the expression of p-eNOS/eNOS from vascular tissues were ascertained. We demonstrate that, during stress, E2 prevented excessive weight gain and OVX rats had higher blood pressures than those in the Sham group. Further, we showed that E2 decreases ET-1 expressions during stress while upregulating NO expressions via enhancing eNOS activities to facilitate vasomotor functions. Finally, histological assessment revealed the E2 treatments during stress preserved vasomotor functions by preventing excessive intima-media thickening and collagen depositions in the aortic vascular walls.

Estrogen Attenuates Chronic Stress-Induced Cardiomyopathy by Adaptively Regulating Macrophage Polarizations via β2-Adrenergic Receptor Modulation

“…The estrous cycle in the Shams causing alterations in E 2E ndo levels while E 2E xo treatment dosage used remained constant might also account for the shown slight variations in E 2E ndo and E 2E xo effects. Therefore, we stand with Zhang et al (2021) in suggesting that E 2 RT should be given at dosages that mimic the concentrations of the estrous cycle to eliminate the observed variations in its cardioprotection efficacy. This will enhance the exploitation of the therapeutic potentials of E 2 RT in attenuation/prevention of CSC via immunomodulation in postmenopausal women.…”

“…All standard animal house boundary protocols were observed. After ensuring the SD rats were in the same menstrual phase through vaginal mucus examination, bilateral ovariectomy (OVX) and sham surgeries were done as we previously described ( Zhang et al, 2021 ).…”

“…As illustrated ( Figure 1A ), 2 weeks after ovariectomy, the rats were intraperitoneally injected with 40 μg/kg/day of estradiol (E 2 ) (E2758; Sigma, St. Louis, MO, United States) for 31 days, as done previously ( Zhang et al, 2021 ). Olive oils of equivalent amounts were administered as a placebo to the control groups.…”

“…The dosage of E 2 employed was to mimic its physiological levels in rats, as we had demonstrated previously ( Liu et al, 2012 ; Zhang et al, 2021 ). Also, rather than the high dosage of ISO used in acute stress models, as done previously ( Youssef et al, 2021 ), a relatively milder dosage was used due to the prolonged duration (10 days) of the catecholamine treatment ( Zhang et al, 2021 ).…”

“…The myocardial sectionings were deparaffinized before performing Masson’s trichrome (Maxim Biotechnologies, Fuzhou, China), hematoxylin and eosin (H&E), and immunohistochemical (IHC) staining as previously described ( Zhang et al, 2021 ). The trichome staining were done to ascertain the collagen volume fraction (CVF) while H&E staining were done to assess cardiomyocyte diameters and help depict the extent of myocardial hypertrophy.…”