Abstract
We evaluated the protective effects of long-term treatment with betaxolol, a specific β1-antagonist, on platelet-derived growth factor (PDGF) A-chain and transforming growth factor (TGF)-β1 gene expression in the left ventricle of Dahl salt-sensitive hypertensive rats fed a high-salt diet. In addition, we evaluated the relations between these effects and coronary microvascular remodeling, expression of extracellular signal-regulated kinases (ERK) belonging to one subfamily of mitogen-activated protein kinases, and expression of p70S6 kinase belonging to one subfamily of ribosomal S6 kinases. Betaxolol (0.9 mg⁄kg⁄day, subdepressor dose) was administered for 5 weeks, from 6 weeks of age to the left ventricular hypertrophy stage at 11 weeks of age. Increased PDGF A-chain and TGF-β1 mRNA and protein expression were suppressed by betaxolol. Upregulated activities of ERK1⁄2 and p70S6 kinase phosphorylations were decreased by betaxolol. Betaxolol administration resulted in significant improvements in the wall-to-lumen ratio, perivascular fibrosis and myocardial fibrosis. Thus, we conclude that ERK1⁄2 and p70S6 kinase activities may play a key role in coronary microvascular remodeling of Dahl salt-sensitive hypertensive rats, and that beneficial effects of betaxolol on cardiovascular remodeling may be at least partially mediated by decreased PDGF A-chain and TGF-β1 expression in the left ventricle. (Hypertens Res 2002; 25: 211-219)
