Daidzein- A Caveolin Inhibitor Exerts Antihypertensive Effect and Improves Endothelium-Dependent Vasorelaxation in a Rat Model of DOCA-Salt-Induced Hypertension

Abstract

Daidzein- A caveolin inhibitor has antioxidant properties that could improve redox-sensitive vascular, cardiac and renal changes associated with deoxycorticosterone acetate/1% NaCl high salt (DOCA/HS)-induced hypertension. We investigated the possible involvement of caveolin and daidzein its inhibitor in hypertension and endothelial dysfunction in a mineralocorticoid-salt mouse model (DOCA-Salt). Hypertension was induced in sham control mice by nephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment for 6-weeks. (Control uninephrectomized mice drank 1% NaCl water). Nephrectomy + DOCA (40mg/kg, s.c: 6 weeks) administration increased mean arterial blood pressure in rats after 6 weeks as compared to normal control group. VED was assessed in terms of decreased serum nitrite/nitrate conc., reduced glutathione levels, ACh-induced endothelium-dependent vasorelaxation, and SNP-induced endothelium-independent Vasorelaxation. These rats received cotreatment of different doses of daidzein (0.2, 0.4mg/kg/day, sac) for 5 weeks. Daidzein (0.2mg/kg/day., and 0.4 mg/kg/day., sac for 1 week) and lisinopril 1mg/kg., p.o., 1 week) treatment for one week significantly ameliorated VED in hypertensive rats measured in terms of decreased reduced glutathione level, serum nitrite/nitrate conc. increased Ach-induced endothelium-dependent vasorelaxation as compared to the hypertensive group. However, sodium nitroprusside did not produce any change in SNP-induced endothelium-independent vasorelaxation that shows that effect is specifically due to the improvement of endothelium dysfunction. Our results demonstrate that daidzein reduces oxidative stress, prevents development and progression of hypertension as well as cardiac and renal hypertrophy in DOCA/HS-induced hypertension via modulation of activated eNOS, endogenous antioxidants, serum NO.