57 Novel roles for dietary nitrate in non ischaemic dilated cardiomyopathy and resistant hypertension

Abstract

Introduction Non ischaemic dilated cardiomyopathy (NIDCM) and resistant hypertension (HTN) are common, chronic diseases. Blood nitrate/nitrite indicate nitric oxide (NO) bioavailability and levels are typically lower in NIDCM and HTN compared to controls indicating perturbed nitric oxide (NO) metabolism. In addition to the well-characterised L-arginine-NO synthase pathway, a second independent pathway for NO synthesis in vivo has been recently discovered whereby dietary nitrate is reduced to nitrite and consequently NO. Exploitation of this pathway represents a promising strategy for increasing NO bioavailability, with possible physiological benefits. Methods To assess effects in HTN, 19 eligible subjects wore an ambulatory blood pressure (BP) monitor (ABPM) for 24 h and fasting blood was taken before and after 14 d of nitrate-rich beetroot juice (BRJ). To assess effects in NIDCM, we recorded exercise capacity (incremental shuttle walk test) and BP before and 3 h after both BRJ and placebo in a randomised, double-blind, crossover trial among 11 subjects. There was 7 d between testing days with the alternate beverage. Results In the HTN study, 11 subjects had controlled blood pressure while 8 had uncontrolled blood pressure. There were similar increases in serum nitrate (p = 0.01) and nitrite (p = 0.001) in both controlled and uncontrolled hypertension. Further, there were no differences in either group regarding serum lipids (triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol). We observed very little chance in BP variables among the controlled hypertensives. In contrast, there were reductions in 24 h, daytime, and nighttime BP as well an increase in nocturnal BP dipping. The decreases in mean nighttime DBP and ambulatory arterial stiffness index (AASI) reached significance (p = 0.03 and p = 0.05 respectively). In the NIDCM trial, there were no significant differences in heart rate, arterial oxygen concentrations, breathlessness, leg fatigue or blood pressure at any time point with either beverage. However, NIDCM subjects walked significantly when took BRJ (+65 m) than when they took PL (-5 m) (p = 0.006). Conclusions Dietary nitrate has potential as a novel therapeutic, adjunct strategy to increase NO bioavailability in cardiovascular disease with potential physiological benefits. Our preliminary results require confirmation in larger trials. However, considering the low cost and safety profile of dietary nitrate containing foods and supplements, this concept appears promising as an adjunct therapeutic strategy for cardiovascular diseases.