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Cardiovascular Research 2003 60(1):147-155; doi:10.1016/S0008-6363(03)00364-X
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

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

Ezia Rugaa, Sergio Bovab,*, Gastone Nussdorferc, Giuseppina Mazzocchic, Piera Rebuffatc, Ornella Milanesia and Gabriella Cargnellib

aDepartment of Pediatrics, University of Padova, Padova, Italy
bDepartment of Pharmacology and Anesthesiology, University of Padova, Padova, Italy
cDepartment of Human Anatomy and Physiology, University of Padova, Padova, Italy

*Corresponding author. Department of Pharmacology and Anesthesiology, L.go E. Meneghetti 2, 35131 Padova, Italy. Tel.: +39-049-827-5098; fax: +39-049-827-5093. Email address: sergio.bova{at}unipd.it

Objective: We investigated the effects of zidovudine (AZT) on cardiac and vascular smooth muscle function and morphology in rats. Methods: 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. Results: 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. Conclusions: 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.

KEYWORDS Blood pressure; Contractile function; Electron microscopy; Heart; Mitochondria; Smooth muscle; Zidovudine

Time for primary review 28 days.


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