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

Acute increases in blood pressure (BP) increase myocardial tumor necrosis f actor (TNF)-alpha production, but it is not known whether chronic hypertens ive stress elevates myocardial TNF-alpha production, possibly contributing to cardiac remodeling, decreased cardiac function, and faster progression t o heart failure. BP, cardiac function, and size were evaluated in normotens ive [Sprague-Dawley (SD)], spontaneously hypertensive (SHR), and spontaneou sly 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 secre tion of bioactive TNF-alpha and inhibition of TNF-alpha secretion by phosph odiesterase inhibitors. All ventricles secreted bioactive and immunoreactiv e TNF-alpha, but secretion decreased with age. SHR and SHHF rats secreted m ore TNF-alpha than SD rats at 6 mo of age, but only failing SHHF rats secre ted significantly more TNF-alpha at 18 mo. Amrinone inhibited TNF-alpha sec retion 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 ele vated myocardial TNF-alpha, and, although hypertension, per se, did not mai ntain elevated cardiac TNF-alpha levels, SHHF rats increase TNF-alpha produ ction during the end stages of failure.