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Revista chilena de cardiología

versión On-line ISSN 0718-8560

Resumen

NOVOA, Ulises; OCARANZA, María Paz; MORA, Italo  y  JALIL, Jorge. Effectiveness of the combined use of a Rho-kinase inhibitor and an Angiotensin II receptor antagonist in the prevention of left ventricular hypertrophy in hypertensive rats. Rev Chil Cardiol [online]. 2010, vol.29, n.2, pp.221-232. ISSN 0718-8560.  http://dx.doi.org/10.4067/S0718-85602010000200008.

Background: The effect of cardiac Rho-kinase (ROCK) on hypertension (HT) and cardiac hypertrophy prevention and also the combined anti-hypertensive treatment have been scarcely studied. We hypothesized that the addition of a ROCK inhibitor to conventional anti-hypertensive treatment may have additional beneficial effects. Ainv to determine ventricular ROCK activity and ventricular remodeling in hypertensive rats treated with Angiotensin II inhibition with the addition of a ROCK inhibitor. Methods: Sprague-Dawley rats weighing 150 grams had one kidney removed and received deoxycortisterone acétate (DOCA, 100 mg/kg/week, during 6 weeks). Unilaterally nephrectomized rats were used as controls. The other 3 groups received DOCA along with the Angiotensin II receptor blocker candesartan (10 mg/kg/day) or the combination of both agents (5 and 25 mg/kg/day, respectively) and ROCK inhibitor fasudil (50 mg/kg/day) for 3 weeks starting 3 weeks after surgery. Body mass (BM), systolic blood pressure (SBP) and relative cardiac mass (RCM) were measured. In addition, myosin phosphatase (MYPT-1) phosphorylation was measured as an indicator of ROCK activation. Cardiac infiltration of macrophages/monocytes (ED1 positive cells), collagen I protein contení (by Western Blot) and also cardiac gene expression of NADPH oxydase GP91 subunit and eNOS were determined by RT-PCR. Results: In hypertensive rats we observed cardiac hypertrophy by 63% (p < 0.05), a 300% increase in cardiac MYPT-1 phosphorylation (p< 0.05), 14 times increase in myocardial collagen type 1,270% increase in ED1 cells, a 75% increased gene expression of NADPH oxydase GP91 subunit and a 37% reduction (p< 0.05) in the gene expression of cardiac eNOS. In hypertensive DOCA rats treated during 3 week with candesartan, fasudil or the combination of both, we observed a significant reduction in cardiac hypertrophy and normalization of SBP, MYPT-1 phosphorylation, collagen type I, number of ED1 cells, genic expression of NADPH oxydase GP91 subunit and in the genic expression of cardiac eNOS. Conclusión: The combined use of a ROCK inhibitor and a low dose Angiotensin II receptor blocker was as effective as full doses of both isolated agents in the prevention of cardiac hypertrophy and hypertensive experimental cardiac remodeling (Fondecyt 1085208)

Palabras clave : Rho-kinase; Angiotensin II receptor antagonist; left ventricular hypertrophy.

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