Hesperidin inhibits L-NAME-induced vascular and renal alterations in rats by suppressing the renin-angiotensin system, transforming growth factor-β1, and oxidative stress.

The protective effect of hesperidin on vascular and renal alterations and possible underlying mechanisms involved in Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats were investigated in this study. Male Sprague-Dawley rats were administered L-NAME (40 mg/kg/day), L-NAME plus hesperidin (30 mg/kg/day), and L-NAME plus captopril (2.5 mg/kg/day) for 5 weeks. Hesperidin and captopril significantly prevented L-NAME-induced hypertension, vascular and renal dysfunction, intrarenal artery remodelling, glomerular extracellular matrix accumulation, and renal fibrosis. The preventive treatment with hesperidin and captopril also significantly decreased serum angiotensin-converting enzyme activity and plasma transforming growth factor-β1 (TGF-β1) levels and downregulated angiotensin II receptor type I and TGF-β1 protein expression in the kidneys. In addition, decreased malondialdehyde levels and increased superoxide dismutase activity in the plasma and kidney were observed after co-treatment with hesperidin or captopril. These findings suggest that hesperidin inhibits L-NAME-induced vascular and renal alterations in rats. The possible mechanism may be related to the suppression of the activation of the renin-angiotensin system and expression of TGF-β1, and reduction of oxidative stress.

Bunbupha S ，Apaijit K ，Potue P ，Maneesai P ，Pakdeechote P ... -  《-》

Hesperidin Prevents Nitric Oxide Deficiency-Induced Cardiovascular Remodeling in Rats via Suppressing TGF-β1 and MMPs Protein Expression.

Maneesai P ，Bunbupha S ，Potue P ，Berkban T ，Kukongviriyapan U ，Kukongviriyapan V ，Prachaney P ，Pakdeechote P ... -  《Nutrients》

Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in L-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT₁R Expression.

Maneesai P ，Prasarttong P ，Bunbupha S ，Kukongviriyapan U ，Kukongviriyapan V ，Tangsucharit P ，Prachaney P ，Pakdeechote P ... -  《Nutrients》

Carthamus Tinctorius L. extract attenuates cardiac remodeling in L-NAME-induced hypertensive rats by inhibiting the NADPH oxidase-mediated TGF-β1 and MMP-9 pathway.

Carthamus tinctorius L. (CT) has been widely used in Asian countries as a beverage and a folk medicine. The current study investigates the effect of CT extract on cardiac remodeling and possible mechanisms involved in Nw-nitro-l-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats were administrated with L-NAME (40mg/kg/day) for five weeks to induce hypertension. Hypertensive rats were treated with CT extract (300mg/kg/day) or captopril (5mg/kg/day) or vehicle for a further two weeks. Treatment of hypertensive rats with CT extract or captopril significantly decreased systolic blood pressure, left ventricular (LV) hypertrophy and fibrosis, small intramyocardial coronary artery remodeling, and cardiac weight index. CT extract or captopril increased plasma nitric oxide metabolite (NOx) levels and reduced plasma transforming growth factor β1 (TGF-β1) level, together with downregulation of cardiac TGF-β1 and matrix metalloproteinases-9 (MMP-9) expression. In addition, decreased plasma malondialdehyde (MDA) levels, consistent with downregulation of NADPH oxidase subunit gp91phox expression in heart tissue, was also observed after CT extract or captopril treatment. These findings suggest that CT extract alleviates cardiac remodeling in L-NAME-induced hypertensive rats, which is possibly related to inhibition of the NADPH oxidase-mediated TGF-β1-MMP-9 pathway.

Bunbupha S ，Pakdeechote P ，Maneesai P ，Prachaney P ，Boonprom P ... -  《-》

Locally activated renin-angiotensin system associated with TGF-beta1 as a major factor for renal injury induced by chronic inhibition of nitric oxide synthase in rats.

:Chronic inhibition of nitric oxide synthase (NOS) is known to cause renal parenchymal injury with systemic hypertension. To elucidate the pathogenetic mechanism in renal damage induced by NOS inhibition, N(omega)-nitro-L-arginine methyl ester (L-NAME) was given orally for 12 wk in Wistar rats, and the roles of tissue renin-angiotensin system and transforming growth factor-beta1 (TGF-beta1) were investigated. BP and urinary protein excretion increased significantly in L-NAME rats compared with control rats, and glomerulosclerosis and interstitial fibrosis developed. In L-NAME rats, the cortical tissue levels of angiotensin-converting enzyme activity and angiotensin II were significantly higher than those in control rats. The cortical mRNA expressions of both TGF-beta1 and fibronectin were significantly elevated in L-NAME rats. Immunohistochemically, increased expressions of both fibronectin and alpha-smooth muscle actin were also revealed in L-NAME rats. In L-NAME rats, these histologic injuries and the increased expression of TGF-beta1 were equally ameliorated by either angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist, but not by hydralazine. In conclusion, the locally activated renin-angiotensin system in connection with the increased TGF-beta1 expression is a major pathogenetic feature of renal injury in chronically NOS-inhibited rats.

Kashiwagi M ，Shinozaki M ，Hirakata H ，Tamaki K ，Hirano T ，Tokumoto M ，Goto H ，Okuda S ，Fujishima M ... -  《JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY》