Integrative cardiovascular study of adaptations induced by early ovariectomy in the hypertensive heart

Ovarian hormone deprivation may exacerbate hypertension-induced cardiac morphofunctional impairments. However, its effects on left ventricular contractility remain unclear. Herein, we investigated the effects of ovariectomy on hemodynamics, cardiac morphology, and function in vivo and ex vivo in isolated hearts of hypertensive rats (spontaneously hypertensive rats, SHRs) and compared these effects with those observed in normotensive controls (Wistar Kyoto, WKY). Eighteen-week-old SHR (n = 32) and WKY (n = 32) underwent ovariectomy or SHAM surgery. At 34 wk, groups were evaluated for hemodynamics using tail plethysmography, cardiac morphology, function by echocardiography, left ventricular contractility by the Langendorff technique, and fibrosis by histological examination. Two-way ANOVA revealed that SHR had reduced body mass and elevated blood pressure at baseline and after 16 wk of ovarian hormone deprivation. In addition, ovariectomy increased body mass and cardiac mass. Regarding cardiac morphofunctional analysis in vivo, SHR exhibited increased intraventricular septum thickness and reduced ejection and shortening fraction. In turn, ovariectomy increased heart rate and reduced stroke volume. The Langendorff technique demonstrated that the SHR exhibited increased coronary perfusion pressure, as well as reduced maximal derivatives of left ventricular pressure (dP/dT_max) and minimal derivatives of left ventricular pressure (dP/dT_min) in response to increased coronary flow. In addition, it showed reduced left ventricular pressure in response to dobutamine and salbutamol. Meanwhile, ovariectomy reduced the flow-mediated responses of left ventricular pressure, dP/dT_max, and dP/dT_min and increased the response of left ventricular pressure to dobutamine. Finally, left ventricular fibrosis was increased in SHR and ovariectomized rats. In conclusion, early ovarian hormone deprivation impaired cardiac morphology and function in normotensive and hypertensive rats, with the most prominent functional impairments observed in isolated hearts. These findings underscore the substantial impact of hormonal status on cardiac function, particularly in the context of hypertension.NEW & NOTEWORTHY This study reveals that early ovarian hormone deprivation worsens cardiac morphology and function in both normotensive and hypertensive rats. Using in vivo and ex vivo assessments, we found that the most pronounced effects of ovariectomy-namely, impaired left ventricular contractility and increased cardiac fibrosis-were observed in isolated hearts. These results underscore the synergistic detrimental impact of hypertension and ovarian hormone loss on cardiac health, reinforcing the importance of hormonal status in the progression of cardiovascular disease.