期刊
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
卷 56, 期 2, 页码 203-211出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0b013e3181e92a01
关键词
aldosterone receptor blockade; adrenergic activation; hypertension; myocardial interstitium; apoptosis
资金
- South African National Research Foundation
- Medical Research Council of South Africa
Although in hypertension beta-adrenoreceptor activation promotes the transition from cardiac hypertrophy to pump dysfunction, the use of b-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 MMPexpression; 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 beta-adrenoreceptor activation responsible for the transition from concentric cardiac hypertrophy to pump dysfunction in hypertension.
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