Effects of adrenergic receptor antagonists on cardiac morphological and functional alterations in rats harboring pheochromocytoma.
New England Deaconness Hospital rats harboring a transplantable pheochromocytoma exhibit plasma norepinephrine concentrations 20-fold higher than controls. A cardiomyopathy (CM) characterized by multifocal areas of interstitial and replacement fibrosis, mixed inflammatory infiltrates and contraction band necrosis is evident 35 to 45 days after tumor implantation. Using a morphological scoring system of 0 (no cardiac damage) to 3 (involvement of almost the complete ventricular cross-section sampled), a CM score of 1.8 +/- 0.1 was found in rats harboring pheochromocytoma, a significant increase over that in age- and sex-matched controls (0.4 +/- 0.1, P less than .001). The pheochromocytoma rats also had hypertension (systolic blood pressure = 182 +/- 4 vs. 131 +/- 2 mm Hg in controls, P less than .001). In an effort to prevent the CM, rats harboring pheochromocytoma were treated with either the beta receptor antagonist timolol, the alpha receptor antagonists phentolamine or phenoxybenzamine or the nonspecific vasodilator hydralazine. Hydralazine normalized systolic blood pressure (135 +/- 6 mm Hg), whereas timolol (144 +/- 5 mm Hg), phenoxybenzamine (166 +/- 5 mm Hg) or phentolamine (154 +/- 10 mm Hg) only moderately decreased blood pressure in rats harboring pheochromocytoma. Hydralazine had no effect on CM score (1.8 +/- 0.1). Timolol markedly attenuated the CM score (0.6 +/- 0.1), whereas the alpha adrenergic antagonists were not as effective (phenoxybenzamine CM score = 1.3 +/- 0.2; phentolamine CM score = 1.7 +/- 0.2). Furthermore, timolol prevented desensitization of beta adrenergic receptor-mediated contraction in the hearts of rats harboring pheochromocytoma.(ABSTRACT TRUNCATED AT 250 WORDS)
D000310:Adrenal Gland Neoplasms / Q000150:complications* / Q000503:physiopathology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology*; D006339:Heart Rate; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000150:complications; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010673:Pheochromocytoma / Q000150:complications* / Q000503:physiopathology; D051381:Rats; D013999:Timolol / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D010643:Phenoxybenzamine; D006830:Hydralazine; D013999:Timolol; D009638:Norepinephrine; D010646:Phentolamine