Zidovudine-induced alterations in the heart and vascular smooth muscle of the rat

• Published in: Cardiovascular research 2003-10, Vol.60 (1), p.147-155
• Main Authors: RUGA, Ezia, BOVA, Sergio, NUSSDORFER, Gastone, MAZZOCCHI, Giuseppina, REBUFFAT, Piera, MILANESI, Ornella, CARGNELLI, Gabriella
• Format: Article
• Language: English
• Subjects: Animals; Anti-HIV Agents - pharmacology; Aorta - drug effects; Biological and medical sciences; Carbachol - pharmacology; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Echocardiography; Endothelium, Vascular - drug effects; Heart - drug effects; Heart Ventricles - ultrastructure; In Vitro Techniques; Male; Medical sciences; Microscopy, Electron; Muscle, Smooth, Vascular - drug effects; Myocardial Contraction - drug effects; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - ultrastructure; Pharmacology. Drug treatments; Phenylephrine - pharmacology; Potassium Chloride - pharmacology; Rats; Rats, Inbred WKY; Toxicity: cardiovascular system; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - pharmacology; Zidovudine - pharmacology
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/S0008-6363(03)00364-X

We investigated the effects of zidovudine (AZT) on cardiac and vascular smooth muscle function and morphology in rats. Four adult male Wistar-Kyoto rats received AZT in drinking water for 240 days; four rats served as controls. Echocardiographic examination and systolic blood pressure (SBP) measurement were performed. At the end of treatment the rats were sacrificed, their hearts were weighed and vascular smooth muscle contractile and relaxing properties were evaluated in vitro on endothelium-intact aortic rings. Morphological studies were performed on cardiac and aortic myocytes by light and electron microscopy. AZT-treated rats (AZT-Rs) showed higher SBP, greater heart weight and, as revealed by echocardiography, greater interventricular septum thickness. Electron microscopy revealed mitochondrial swelling in myocardiocytes in AZT-Rs. Reduced response to contractile stimuli and enhanced relaxation in response to charbacol were observed in the aortic rings of AZT-Rs. The aortic myocytes of AZT-Rs contained apparently unaffected ultrastructural features, but light microscopy suggested their marked enlargement. AZT treatment for 240 days in rats induces a modest increase in SBP, hypertrophy of the interventricular septum and modified vascular smooth muscle responsiveness. The role of mitochondria in these AZT-induced cardiovascular alterations remains to be established.