Bergman M R, Kao R H, McCune S A, Holycross B J
College of Pharmacy, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Columbus, Ohio 43210, USA.
Am J Physiol. 1999 Aug;277(2):H543-50. doi: 10.1152/ajpheart.1999.277.2.H543.
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.
