Vascular smooth muscle cell polyploidy and cardiomyocyte hypertrophy due to chronic NOS inhibition in vivo

Devlin, A. M., Brosnan, M. J., Graham, D. , Morton, J. J., McPhaden, A. R., McIntyre, M., Hamilton, C. A., Reid, J. L. and Dominiczak, A. F. (1998) Vascular smooth muscle cell polyploidy and cardiomyocyte hypertrophy due to chronic NOS inhibition in vivo. American Journal of Physiology: Heart and Circulatory Physiology, 274(1), H52-H59. (PMID:9458851)

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Publisher's URL: http://ajpheart.physiology.org/content/274/1/H52

Abstract

To assess the vascular and cardiac response to NO (nitric oxide) synthase (NOS) blockade in vivo, Wistar-Kyoto rats (WKY) were treated for 3 wk withN G-nitro-L-arginine methyl ester (L-NAME; 10 mg ⋅ kg−1 ⋅ day−1).L-NAME treatment induced hypertension that was associated with increased plasma renin activity. Flow cytometry cell cycle DNA analysis showed that aortic vascular smooth muscle cells (VSMC) fromL-NAME-treated WKY had a significantly higher polyploid population compared with WKY controls. Using organ bath experiments, we have shown that aortic rings fromL-NAME-treated WKY have an increased contractile response to phenylephrine and impaired relaxation to carbachol compared with control rings. NOS blockade in vivo caused a significant increase in cardiac and left ventricular hypertrophy. Northern mRNA analysis of the myocardium showed thatL-NAME treatment caused reexpression of the fetal skeletal α-actin isoform without alterations in collagen type I expression, a pattern indicating true hypertrophy of the cardiomyocytes. These studies provide further insight to confirm that NO deficiency in vivo results in the development of vascular and cardiac hypertrophy.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Graham, Dr Delyth and Hamilton, Dr Carlene and Dominiczak, Professor Anna and Morton, Dr James and McIntyre, Dr Martin and McPhaden, Dr Allan and Reid, Professor John
Authors: Devlin, A. M., Brosnan, M. J., Graham, D., Morton, J. J., McPhaden, A. R., McIntyre, M., Hamilton, C. A., Reid, J. L., and Dominiczak, A. F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > General Practice and Primary Care
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > MRC/CSO Unit
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:American Journal of Physiology: Heart and Circulatory Physiology
Journal Abbr.:AJP: Heart and circulatory physiology
Publisher:American Physiological Society
ISSN:0363-6135
ISSN (Online):1522-1539

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