Ovariectomy augments pressure overload-induced hypertrophy associated with changes in Akt and nitric oxide synthase signaling pathways in female rats.

Abstract

To elucidate the molecular mechanism underlying estrogen-mediated cardioprotection in left ventricular (LV) hypertrophy and remodeling, we analyzed myocardial hypertrophy as well as cardiac function and hypertrophy-related protein expression in ovariectomized, aortic-banded rats. Wistar rats subjected to bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis. Effects on LV morphology and function were assessed using echocardiography, and expression of protein levels was determined by Western blot analysis. The heart-to-body weight ratio was most significantly increased in the OVX-pressure overload (PO) group compared with the OVX group and in the PO group compared with sham. The LV weight-to-body weight ratio was also significantly increased in the OVX-PO group compared with the OVX group and in the PO group compared with sham. The most significant increases in LV end diastolic pressure, LV developed pressure, and +/-dp/dt(max) were observed in the OVX-PO group compared with the OVX group and represent compensatory phenotypes against hypertrophy. Both endothelial nitric oxide (eNOS) synthase expression and activity was markedly reduced in the OVX-PO group, and protein kinase B (Akt) activity was largely attenuated. Marked breakdown of dystrophin was also seen in hearts of OVX-PO groups. Finally, significantly increased mortality was observed in the OVX-PO group following chronic isoproterenol administration. Our results demonstrate that rats subjected to ovariectomy are unable to compensate for hypertrophy, showed deteriorated heart function, and demonstrated increased mortality. Simultaneous impairment of eNOS and Akt activities and reduced dystrophin by ovariectomy likely contribute to cardiac decompensation during PO-induced hypertrophy in ovariectomized rats.

• Authors: Md Shenuarin Bhuiyan, Norifumi Shioda, Kohji Fukunaga
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 293 Issue 6 Pg. E1606-14 (Dec 2007) ISSN: 0193-1849 [Print] United States
• PMID: 17878225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cav3 protein, rat
• Caveolin 3
• Dystrophin
• Estrogens
• Heat-Shock Proteins
• Myosin Light Chains
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type III
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases
• Isoproterenol

Topics

• Animals
• Aorta, Abdominal (surgery)
• Aortic Valve Stenosis (complications)
• Blood Pressure (physiology)
• Body Weight (physiology)
• Caveolin 3 (metabolism)
• Dystrophin (metabolism)
• Estrogens (blood)
• Female
• Heart (drug effects, physiopathology)
• Heart Rate (physiology)
• Heat-Shock Proteins (metabolism)
• Hypertrophy, Left Ventricular (etiology, metabolism, physiopathology)
• Isoproterenol (pharmacology)
• Myocardium (metabolism, pathology)
• Myosin Light Chains (metabolism)
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Ovariectomy
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Wistar
• Survival Analysis
• p38 Mitogen-Activated Protein Kinases (metabolism)