(-)-Epicatechin Reduces Blood Pressure and Improves Left Ventricular Function and Compliance in Deoxycorticosterone Acetate-Salt Hypertensive Rats

Abstract

(−)-Epicatechin (E) is a flavanol found in green tea and cocoa and has been shown to attenuate tumour necrosis factor alpha (TNF-α)-mediated inflammation, improve nitric oxide levels, promote endothelial nitric oxide synthase (eNOS) activation and inhibit NADPH oxidase. This study investigated the effect of 28 days of low epicatechin dosing (1 mg/kg/day) on the cardiovascular function of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Wistar rats (n = 120, 8 weeks of age) underwent uninephrectomy and were randomised into four groups (uninephrectomy (UNX), UNX + E, DOCA, DOCA + E). DOCA and DOCA + E rats received 1% NaCl drinking water along with subcutaneous injections of 25 mg deoxycorticosterone-acetate (in 0.4 mL of dimethylformamide) every fourth day. UNX + E and DOCA + E rats received 1 mg/kg/day of epicatechin by oral gavage. Single-cell micro-electrode electrophysiology, Langendorff isolated-heart assessment and isolated aorta and mesenteric organ baths were used to assess cardiovascular parameters. Serum malondialdehyde concentration was used as a marker of oxidative stress. Myocardial stiffness was increased and left ventricular compliance significantly diminished in the DOCA control group, and these changes were attenuated by epicatechin treatment (p < 0.05). Additionally, the DOCA + E rats showed significantly reduced blood pressure and malondialdehyde concentrations; however, there was no improvement in left ventricular hypertrophy, electrophysiology or vascular function. This study demonstrates the ability of epicatechin to reduce blood pressure, prevent myocardial stiffening and preserve cardiac compliance in hypertrophied DOCA-salt rat hearts.

Keywords: DOCA-salt; cardiac function; electrophysiology; epicatechin; hypertension.

Figure 1

Vascular isolated organ bath experiments. (a) Aorta concentration response curve to NA; (b) Aorta concentration response curve to ACh following sub-maximal pre-contraction with NA; responses are presented as percentage of pre-contractile force; (c) Aorta concentration response curve to NaNO following sub-maximal pre-contraction with NA; responses are presented as the percentage of pre-contractile force; (d) Mesenteric concentration response curve to NA; (e) Mesenteric concentration response curve to ACh following submaximal precontraction with NA; responses are presented as the percentage of pre-contractile force; (f) Mesenteric concentration response curve to NaNO following submaximal precontraction with NA; responses are presented as the percentage of pre-contractile force. ^a p < 0.05 compared to UNX; ^b p < 0.05 compared to DOCA.