Veliotes D.G.A., Norton G.R., Correia R.J., Strijdom H., Badenhorst D., Brooksbank R., Woodiwiss A.J.
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193, Johannesburg, South Africa; Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa
Veliotes, D.G.A., Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193, Johannesburg, South Africa; Norton, G.R., Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193, Johannesburg, South Africa; Correia, R.J., Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193, Johannesburg, South Africa; Strijdom, H., Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa; Badenhorst, D., Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193, Johannesburg, South Africa; Brooksbank, R., Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193, Johannesburg, South Africa; Woodiwiss, A.J., Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193, Johannesburg, South Africa
Although in hypertension β-adrenoreceptor activation promotes the transition from cardiac hypertrophy to pump dysfunction, the use of β-blockers is controversial. As adrenergic activation may mediate adverse effects on the heart through the renin-angiotensin-aldosterone system, we evaluated the effects of the aldosterone receptor blocker, spironolactone (SPIRO), on isoproterenol (ISO)-induced changes in left ventricular cavity size and pump function and the determinants thereof in spontaneously hypertensive rats (SHR). ISO administered for 4.5 months resulted in increases in left ventricular dimensions and a decrease in pump function in SHR but not in normotensive rats, changes that, without affecting blood pressure, were abolished by SPIRO. In SHR, 4-5 days of ISO increased myocardial matrix metalloproteinase-2 activity, which was associated with matrix metalloproteinase-2 but not tissue inhibitor of MMP expression; persisted at 4.5 months; and was prevented by SPIRO. Moreover, after 4.5 months, ISO increased non-cross-linked myocardial collagen concentrations in SHR, which was abolished by SPIRO. Although after 4.5 months, ISO was not associated with increased cardiomyocyte apoptosis, an early (4-5 days) ISO-induced apoptotic effect was noted, which was prevented by SPIRO. Hence, aldosterone receptor blockade may be sufficient to prevent those adverse effects of β-adrenoreceptor activation responsible for the transition from concentric cardiac hypertrophy to pump dysfunction in hypertension. © 2010 Lippincott Williams & Wilkins, Inc.
collagen; gelatinase A; isoprenaline; spironolactone; tissue inhibitor of metalloproteinase 2; adrenergic activity; adrenergic receptor blocking; animal experiment; animal model; animal tissue; apoptosis; article; cell structure; controlled study; cross linking; diastolic blood pressure; echocardiography; enzyme activity; heart left ventricle contraction; heart left ventricle filling pressure; heart left ventricle hypertrophy; heart left ventricle size; heart muscle cell; heart weight; hypertension; nonhuman; priority journal; protein expression; rat; systolic blood pressure; Adrenergic beta-Agonists; Aldosterone Antagonists; Animals; Apoptosis; Blood Pressure; Cardiomyopathy, Dilated; Hypertension; Hypertrophy, Left Ventricular; Isoproterenol; Matrix Metalloproteinase 2; Myocardial Contraction; Myocardium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Aldosterone; Renin-Angiotensin System; Spironolactone