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

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Bergman MR, Kao RH, McCune SA, Holycross BJ

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

Am J Physiol. 1999 Aug;277(2 Pt 2):H543-50.

PubMed ID

10444479 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amrinone	Tumor necrosis factor	Protein	Humans	Unknown	Inhibitor	Details