Adrenoreceptor blockade in angiotensin-induced hypertension: effect on rat coronary arteries and myocardium.
Adrenoreceptor blockade has been used to separate the actions of elevated blood pressure, angiotensin II, and catecholamines on the coronary vasculature and myocardium of rats. Twenty-two male Wistar-Kyoto rats received phentolamine (an alpha-receptor blocker, 10 mg/kg body weight) and/or propranolol (a beta-receptor blocker, 1 mg/kg body weight) followed by an infusion for 2 hours of angiotensin amide (1.7 micrograms/min/kg) or saline. Sections of left ventricle were examined by light and electron microscopy. Blood pressure was elevated only in animals receiving angiotensin II with or without propranolol. Epicardial arteries were devoid of lesions in all animals. Small intramural arteries and arterioles in the hypertensive animals exhibited vasoconstriction, endothelial cell vacuolization with bleb formation, and medial smooth muscle cell fragmentation and necrosis. Foci of irreversible ischemic or anoxic myocardial injury consisting of contraction zones and bands and translocated mitochondria with granular matrix densities were seen in angiotensin-infused animals. Similar but less severe myocardial changes were found in the animals pretreated with propranolol. Vascular lesions were also seen in animals receiving phentolamine, propranolol, and angiotensin II; but myocardial alterations consisted solely of areas with contraction zones. Vascular but not myocardial lesions were observed in animals that received angiotensin II and phentolamine. It is concluded that angiotensin II can produce vascular injury in the absence of elevated systemic blood pressure or catecholamine effects. In contrast, irreversible myocardial injury seems to depend upon the increased pressure and/or coronary artery vasoconstriction associated with angiotensin administration.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology* / Q000648:ultrastructure; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction
D000317:Adrenergic alpha-Antagonists; D000804:Angiotensin II; D011433:Propranolol; D010646:Phentolamine