The Effect of Indapamide on Development of Myocardial Hypertrophy and Fibrosis in L-NAME-Induced Hypertension in Rat

Abstract

The aim of this study was to analyze the effect of indapamide and its combination with ACE inhibitor (captopril) and antioxidant (ProvinolsTM) on both myocardial hypertrophy and fibrosis. Wistar rats were treated with L-NAME (40 mg/kg/day, L); L-NAME plus indapamide (1 mg/kg/day), or captopril (10 mg/kg/day), or ProvinolsTM (40 mg/kg/day), or combination of indapamide with captopril, and indapamide with ProvinolsTM for 7 weeks. Blood pressure (BP), LV hypertrophy and fibrosis were determined. The content of collagens type I and III was evaluated morphometrically after picrosirius red staining. L-NAME treatment led to increased BP, LV hypertrophy, total fibrosis and relative content of collagens without the change in collagen type I/III ratio. Indapamide and captopril decreased BP, LV hypertrophy and the collagen ratio without affecting total fibrosis, while ProvinolsTM reduced BP, the collagen ratio and fibrosis without affecting LV hypertrophy. The combinations decreased all the parameters. Decrease of LV hypertrophy was achieved by drugs with the best reducing effect on BP, fibrosis reduction was reached by the antioxidant treatment with only partial effect on BP. Thus, the combination of antihypertensive and antioxidant treatment may represent a powerful tool in preventing myocardial remodeling induced by hypertension.

Effect of QiShenYiQi Pill on Myocardial Collagen Metabolism in Rats with Partial Abdominal Aortic Coarctation

“…By contrast, collagen type III mainly forms a slender fiber, and its stretch and rebound resilience are strong [ 19 ]. Increased levels of collagen type I can increase myocardial stiffness, while increased levels of collagen type III can increase ventricular compliance; therefore, the collagen type I/III ratio can be a good reflection of the degree of myocardial fibrosis [ 20 ]. In addition, a variety of myocardial collagen metabolism products, including PICP, PIIINP, and CTX-I, are involved in the process of myocardial fibrosis [ 21 ].…”

Physical training prevents oxidative stress in L‐NAME‐induced hypertension rats

“…L-NAME administration includes via drinking water, gavage and subcutaneous injection. Although most of the works induce hypertension through drinking water, 38,6,[9][10][11][12]8,15 Ribeiro et al 8 observed that average dairy water intake per box was 26% lower in L-NAME-treated rats than in controls. This way, we chose gavage administration to be sure on the dose ingested by rats and to be sure all rats were receiving the same dose.…”

“…[6][7][8] Several studies have administered in vivo an inhibitor of NO biosynthesis, the No-nitro-L-arginine methyl ester hydrochloride (L-NAME), an L-arginine analogue, to induce hypertension in rats. [9][10][11][12][13][14][15] In hypertension, the production of reactive oxygen species (ROS) is increased by various means and it can also cause other vascular diseases and disorders. 16 However, it still remains unclear whether increased ROS levels are a cause or a consequence of high BP.…”

“…Chronic inhibition of NO produces a volume‐dependent elevation of blood pressure (BP) and its physiological and pathological characteristics resemble essential hypertension . Several studies have administered in vivo an inhibitor of NO biosynthesis, the Nω‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME), an L‐arginine analogue, to induce hypertension in rats …”

Chronic aerobic exercise associated to low-dose L-NAME improves contractility without changing calcium handling in rat cardiomyocytes

“…Increases in collagen content may cause myocardial dysfunction due to impairment of the ventricular compliance, as well as changes in cardiac geometry. The literature suggests that decreased NO synthesis promotes the activation of neurohormonal systems and growthpromoting factors that could induce myocardial fibrosis (38). Cardiac hypertrophy refers to the process of cardiac thickening and remodeling, and may be due to cardiac pathology or long-term exercise training.…”