Abstract

This continuation grant will attempt to identify factors important in the development of ventricular hypertrophies, mainly due to exercise and systolic overload either alone and combined. Renal hypertension and chronic swimming in the female rat will be the predominant interventions. We will explore why swimming results in cardiac hypertrophy and increased cardiac myosin isoenzyme v1, while running does not. Hemodynamics, hormones and blood gasses wil be investigated. The biochemistry of cardiac contraction and relaxation will be explored by studying sarcoplasmic reticulum and troponin-tropomyosin. Male and females will be investigated with gonadectomy and sex hormone cross-over studies, to explore why females respond with cardiac hyertrophy to swimming and males do not. The role of diastolic overload, unrelated to exercises, will be explored in combined ventricular hypertrophies using rats with arterivenous fistula. The role of catecholamines in the development of cardiac hypertrophy and the training effect will be studied in rats subjected to chronic dobutamine treatment. The effect of systolic loads, other than renal hypertension, will be investigated, including DOCA-salt hypertension (a low renin, high blood volume form of hypertension) and myocardial infarction (a different type of load) combined with swimming. Senescent rats will be exposed to hypertension and exercise to determine if their hearts respond to combined hypertrophy similarly or differently than hearts of adult rats.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL015498-15
Application #
3334969
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1978-01-01
Project End
1991-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
15
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Montefiore Medical Center (Bronx, NY)
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10467

  Publications

Roman, B B; Geenen, D L; Leitges, M et al. (2001) PKC-beta is not necessary for cardiac hypertrophy. Am J Physiol Heart Circ Physiol 280:H2264-70
Tian, R; Miao, W; Spindler, M et al. (1999) Long-term expression of protein kinase C in adult mouse hearts improves postischemic recovery. Proc Natl Acad Sci U S A 96:13536-41
Shizukuda, Y; Buttrick, P M; Geenen, D L et al. (1998) beta-adrenergic stimulation causes cardiocyte apoptosis: influence of tachycardia and hypertrophy. Am J Physiol 275:H961-8
Rybin, V O; Buttrick, P M; Steinberg, S F (1997) PKC-lambda is the atypical protein kinase C isoform expressed by immature ventricle. Am J Physiol 272:H1636-42
Stenbit, A E; Tsao, T S; Li, J et al. (1997) GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nat Med 3:1096-101
Malhotra, A; Nakouzi, A; Bowman, J et al. (1997) Expression and regulation of mutant forms of cardiac TnI in a reconstituted actomyosin system: role of kinase dependent phosphorylation. Mol Cell Biochem 170:99-107
Malhotra, A; Sanghi, V (1997) Regulation of contractile proteins in diabetic heart. Cardiovasc Res 34:34-40
Bowman, J C; Steinberg, S F; Jiang, T et al. (1997) Expression of protein kinase C beta in the heart causes hypertrophy in adult mice and sudden death in neonates. J Clin Invest 100:2189-95
Siri, F M; Malhotra, A; Factor, S M et al. (1997) Prolonged ejection duration helps to maintain pump performance of the renal-hypertensive-diabetic rat heart: correlations between isolated papillary muscle function and ventricular performance in situ. Cardiovasc Res 34:230-40
Geenen, D L; Malhotra, A; Scheuer, J et al. (1997) Repeated catecholamine surges alter cardiac isomyosin expression but not protein synthesis in the rat heart. J Mol Cell Cardiol 29:2711-6

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