A Newly Developed Angiotensin II Type 1 Receptor Antagonist, CS866, Promotes Regression of Cardiac Hypertrophy by Reducing Integrin .BETA.1 Expression
スポンサーリンク
概要
- 論文の詳細を見る
<B>Previous studies have demonstrated that integrins link the extracellular matrix to the hypertrophic response pathway of cardiac myocytes <I>in vitro</I>. To examine the direct relation between integrin β<SUB>1</SUB> and cardiac hypertrophy <I>in vivo</I>, we studied the effects of a newly developed angiotensin II type 1 (AT<SUB>1</SUB>) blocker, CS866 (ARB; 10 mg/kg/day), an angiotensin-converting enzyme inhibitor, temocapril (ACEI, 10 mg/kg/day), or both on modulation of integrin β<SUB>1</SUB> in the hypertrophied hearts of stroke-prone spontaneously hypertensive rats (SHRSP) 6 to 12 weeks of age. Treatments with ARB, ACEI, and combination therapy significantly reduced systolic blood pressure. However, the reduction in cardiac hypertrophy was greater in SHRSP treated with ARB or combination therapy than in those treated with ACEI. Multiplex reverse transcription-polymerase chain reaction revealed significantly higher mRNA expression of atrial natriuretic factor, AT<SUB>1</SUB> receptor, and integrin β<SUB>1</SUB> in untreated SHRSP than in normotensive Wistar-Kyoto rats (WKY). The mRNA levels of ANP, AT<SUB>1</SUB> receptor, and integrin β<SUB>1</SUB> in SHRSP were significantly decreased by treatment with ARB, ACEI, or combination therapy. Decreased mRNA expression of ANP, AT<SUB>1</SUB> receptor, and integrin β<SUB>1</SUB> in the treated SHRSP was associated with reductions in blood pressure; ARB and combination therapy produced greater decreases in expression than did ACEI. These observations suggest that CS866 has a beneficial effect on myocyte hypertrophy and that down-regulation of AT<SUB>1</SUB> receptor and suppression of integrin β<SUB>1</SUB> participate in the regression of pressure-induced cardiac hypertrophy <I>in vivo</I>. The correlation between the expression of integrin β<SUB>1</SUB> and AT<SUB>1</SUB> receptor was significant. Our results also suggest that integrin expression by myocytes might be modulated by angiotensin II <I>via</I> AT<SUB>1</SUB> receptor. (<I>Hypertens Res </I>2003; 26: 737-742)</B>
- 日本高血圧学会の論文
日本高血圧学会 | 論文
- Telmisartan treatment decreases Visceral Fat Accumulation and improves Serum Levels of Adiponectin and Vascular Inflammation Markers in Japanese Hypertensive Patients.
- The Effects of Verapamil SR and Bisoprolol on Reducing the Sympathetic Nervous System's Activity.
- The Role of Renal Dopamine in the Reduction of High Blood Pressure by β1-Selective β-Blocker with Intrinsic Sympathomimetic Activity in Spontaneously Hypertensive Rats
- Effects of Long-Term Antihypertensive Therapy on Physical Fitness of Men with Mild Hypertension.
- Prediction of Progression of Left Ventricular Hypertrophy in Mild Hypertension: 5-Year Observations without Pharmacological Intervention.