The objective of the research remains the elucidation of the biochemical mechanisms that underly the functional alterations accompanying cardiac hypertrophy. We have shown that the content and fatty acyl composition of phospholipids is altered in the pressure-overload hypertrophied rat heart. Alterations in the phospholipid composition of cellular membranes greatly influences membrane structure and function. The proposed studies are designed to: 1) determine the lipid composition of isolated mitochondrial, sarcoplasmic reticular and sarcolemmal membranes of the hypertrophied rat heart; 2) evaluate the structural and funcitonal consequences of the identified lipid alterations in these membranes; and 3) pursue the mechanisms underlying the acquisition of the changes in membrane lipid composition. Mitochondria, sarcoplasmic reticulum (SR) and sarcolemma (SL) will be isolated from hypertrophied hearts of rats subjected to abdominal aortic constriction. The content and fatty acyl composition of membrane phospholipids will be determined in these isolated subcellular fractions. A variety of membrane and membrane-related functions will be examined in vitro, including mitochondrial respiratory function, mitochondrial Ca++ uptake, SR Ca++ uptake and Ca++ - ATPase activity, SL Na+-Ca++ exchange and beta receptor function. Membrane structure will be examined by evaluating membrane fluidity using electron spin resonance spectroscopy. Studies of myocardial phospholipase and acyltransferase activities will be undertaken to determine if alterations in phospholipid deacylation-reacylation reactions contribute to altered membrane fatty acyl composition in hypertrophied hearts. Myocardial membrane lipid composition and membrane function will also be examined in spontaneously hypertensive rats with the progressive development of pressure overload (hypertension). Studies on membrane lipid metabolism and membrane structure-function relationships in cardiac hypertrohy may facilitate a better understanding of the biochemical factors that contribute to impaired contractile function in the pressure overloaded heart.
| O'Rourke, B; Reibel, D K; Thomas, A P (1992) Alpha-adrenergic modification of the Ca2+ transient and contraction in single rat cardiomyocytes. J Mol Cell Cardiol 24:809-20 |
| O'Rourke, B; Reibel, D K (1992) Effects of adrenoceptor blockade on cardiac hypertrophy and myocardial phospholipids. Proc Soc Exp Biol Med 200:95-100 |
| Foster, K A; Hock, C E; Reibel, D K (1991) Altered responsiveness of hypertrophied rat hearts to alpha- and beta-adrenergic stimulation. J Mol Cell Cardiol 23:91-101 |
| O'Rourke, B; Reibel, D K; Thomas, A P (1990) High-speed digital imaging of cytosolic Ca2+ and contraction in single cardiomyocytes. Am J Physiol 259:H230-42 |
| Reibel, D K; Holahan, M A; Hock, C E (1988) Effects of dietary fish oil on cardiac responsiveness to adrenoceptor stimulation. Am J Physiol 254:H494-9 |
| Hock, C E; Holahan, M A; Reibel, D K (1987) Effect of dietary fish oil on myocardial phospholipids and myocardial ischemic damage. Am J Physiol 252:H554-60 |
