The effects of gonadectomy on left ventricular function and cardiac contractile proteins in male and female rats.

Abstract

To examine the influence of the sex hormones on mechanical properties and biochemistry of the adult heart, we studied left ventricular function and cardiac contractile proteins in hearts from 20-week-old male and female rats that had been gonadectomized at 18 days of age, compared with hearts from sham-operated animals. Testosterone and estradiol were not detectable in serum from male and female gonadectomized rats, respectively. The male rats had lower body and heart weights than male sham operated rats, whereas these values were higher in female gonadectomized than in female sham-operated rats. Left ventricular function was studied in a working heart apparatus at similar heart rate and at controlled levels of aortic diastolic pressure and left atrial pressure. At moderate left atrial pressure, end-diastolic pressure and volume per gram dry left ventricle were the same in all groups, but at high left atrial pressure, end-diastolic pressure, and volume per gram dry left ventricle were lower in male and female gonadectomized than in the respective sham-operated rats. Further increases in left atrial pressure were associated with mechanical alternans in male and female gonadectomized rats. Significantly (P less than 0.05) lower values for cardiac output, peak systolic pressure, ejection fraction, and myocardial oxygen consumption occurred in male gonadectomized compared with sham-operated rats at moderate and high left atrial pressure at higher levels of aortic diastolic pressure. Decreases in these values for female gonadectomized compared with sham-operated rats occurred only at high left atrial pressure. A significant downward shift in the mean force-velocity relationship was observed in all gonadectomized rats at both moderate and high left atrial pressure. In a follow-up study, when end-diastolic pressure was kept the same at both moderate and high left atrial pressure in female sham-operated and gonadectomized rats by reducing heart rate, decreases in contractile function in gonadectomized rats were observed at all preloads. Ca++-myosin ATPase activity was significantly reduced by 34% in male and by 19% in female gonadectomized rats when compared to respective sham-operated control hearts. These alterations in myosin ATPase activity were associated with a reduction in the V1 myosin isoenzyme and an increase in the V3 isoenzyme. Thus, left ventricular filling and left ventricular function were impaired in hearts of gonadectomized rats. Alterations in function were associated with depressed cardiac myosin ATPase activity in male and female gonadectomized rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Superinhibition of Sarcoplasmic Reticulum Function by Phospholamban Induces Cardiac Contractile Failure

“…However, the progression to failure was delayed in females (37), indicating that, despite a similar degree of LV hypertrophy between males and females, there were significant gender differences in the LV-adaptive response to pathological hypertrophy and depressed function, similar to recent studies in the TNF-␣ overexpression model and in a rat model of pressure overload hypertrophy (38). The etiology of these differences is unclear but may be related to: (a) a reduced adaptive hypertrophic reserve in males (39); (b) the lower mitochondria respiratory and lysosomal enzyme activity in females (40); (c) a higher percentage of the V1 myosin isozyme, which is up-regulated by estrogen in females (41); and (d) the intrinsic gender-specific differences in cardiac muscle physiology and biochemistry (42). Furthermore, estrogen signaling through the adult myocyte estrogen receptor may contribute to gender differences in gene expression in pathological hypertrophy (43).…”

The Effects of Biological Sex and Diet on the Development of Heart Failure

“…67 This shift can be reversed by sex-appropriate supplementation. 68 In SHHF rats, ovariectomy followed by estradiol treatment prevents left ventricular hypertrophy and hypertension, which delays the typical onset of CHF in these animals.…”

Adaptive mechanisms of left ventricular diastolic function to the physiologic load of pregnancy

“…Gonadectomy and sex hormone therapy are known to alter LV diastolic performance. 36 A documented difference in diastolic function between middle-aged men and women, and between pre-and postmenopausal women is thought to represent the influence of sex hormones. Specifically, a higher A wave velocity and a lower E/A ratio are seen in postmenopausal women and in men aged > 60 years.…”