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Am J Physiol Heart Circ Physiol 277: H543-H550, 1999;
0363-6135/99 $5.00
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Vol. 277, Issue 2, H543-H550, August 1999

Myocardial tumor necrosis factor-alpha secretion in hypertensive and heart failure-prone rats

Marina R. Bergman1, Ruey H. Kao1, Sylvia A. McCune2, and Bethany J. Holycross3

1 College of Pharmacy; 2 Department of Food Science and Technology, College of Food, Agriculture and Environmental Sciences; and 3 Department of Medical Biochemistry, College of Medicine, The Ohio State University, Columbus, Ohio 43210

Acute increases in blood pressure (BP) increase myocardial tumor necrosis factor (TNF)-alpha production, but it is not known whether chronic hypertensive stress elevates myocardial TNF-alpha production, possibly contributing to cardiac remodeling, decreased cardiac function, and faster progression to heart failure. BP, cardiac function, and size were evaluated in normotensive [Sprague-Dawley (SD)], spontaneously hypertensive (SHR), and spontaneously hypertensive heart failure-prone (SHHF) rats at 6, 12, 15, and 18 mo of age and in failing SHHF. Left ventricular tissues were evaluated for secretion of bioactive TNF-alpha and inhibition of TNF-alpha secretion by phosphodiesterase inhibitors. All ventricles secreted bioactive and immunoreactive TNF-alpha , but secretion decreased with age. SHR and SHHF rats secreted more TNF-alpha than SD rats at 6 mo of age, but only failing SHHF rats secreted significantly more TNF-alpha at 18 mo. Amrinone inhibited TNF-alpha secretion in all rats and was less potent but more efficacious than RO-201724 in all strains. TNF-alpha secretion correlated with BP and left ventricular mass in 6-mo-old rats, but this relationship disappeared with age. Results suggest that hypertension and/or cardiac remodeling is associated with elevated myocardial TNF-alpha , and, although hypertension, per se, did not maintain elevated cardiac TNF-alpha levels, SHHF rats increase TNF-alpha production during the end stages of failure.

spontaneously hypertensive rats; SHHF/Mcc-facp rats; phosphodiesterase inhibitors; amrinone; RO-201724


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