論文ID: JNMS.2021_88-303
Background: Although heart failure (HF) with preserved ejection fraction (HFpEF) is more common in postmenopausal women than in men, the effect of sex hormones on cardiac diastolic function remains unclear. We examined the effect of gonadectomy with or without an angiotensin receptor blocker, olmesartan (Olm), in an isoproterenol (ISO) -induced mouse model of left ventricular hypertrophy (LVH) and cardiac diastolic dysfunction. Methods: ISO or ISO with Olm were administered for 28 days in sham-operated male and female, castrated (CAS), and ovariectomized (OVX) mice. The LV ejection fraction (EF) and E/A ratio were analyzed using echocardiography, and the LV and lung weight corrected by tibial length were determined as indices of LVH and lung congestion, respectively.
Results: On echocardiography, the systolic function did not differ between the four groups. The LV/tibial length (TL) and Lung/TL significantly increased in all groups. The LV/TL was lower in castrated-ISO vs. Male-Sham-ISO, but did not differ between Female-Sham-ISO and OVX-ISO. However, the Lung/TL of OVX-ISO was greater than that of Female-Sham-ISO. Olm prevented LV hypertrophy in all groups. The decreased E/A and increased lung weight were improved by Olm in Male-Sham and OVX-ISO, but not in the others.
Conclusion: These gender differences suggest that sex hormones play a pivotal role in modulating cardiac hypertrophy and diastolic dysfunction induced by chronic beta-adrenoceptor stimulation, thereby affecting the therapeutic potential of angiotensin receptor blockade.
