Effects of citrulline and arginine on blood pressure and heart rate in rat

Blood pressure (BP) is defined as the force exerted by the blood upon any area of the walls of the vessels. Slight increase in blood pressure is normal in daily life, but even mild increase of arterial blood pressure is associated with the heart diseases and subsequently reducing the lifetime (1). Cyclosporine a (CsA) is a fat-soluble and cyclic polypeptide product used as immunosuppressive agent, which hypertension and nephrotoxicity have been reported as its usual adverse effects (2). The CsA related hypertension is infrequently manageable with common available anti-hypertensive agents (3). Different nitric oxide (NO) precursors including arginine and citrulline have been known as an important group of the anti-hypertensive agents (4). Arginine is a semiessential amino acid that oral supplementation of this amino acid has been used in a variety of clinical conditions (5). The citrulline released from arginine and nitric oxide synthase interaction is converted to arginine in different tissues including endothelium (6). This can increases the amount of NO production and improves the cardiovascular activities. This study aimed to compare the effects of citrulline and arginine on CsA-induced hypertension and tachycardia. Forty two Wistar male rats weighing 300-350g were divided into seven experimental groups (N=6).The rats were treated daily with 0.5ml olive oil SC as solvent of CsA (group1), 1ml distilled water (group2), 200 mg/kg citrulline ip (group3), 25mg/kg CsA SC (group4), CsA + citrulline (group5) with the same doses used in the former groups, 200 mg/kg arginine ip (group6), and arginine + CsA with the same doses of group5 (group7) for 7days. Systolic BP and heart rate were measured on the first and the last day of the treatment by a tail-cuff probe using non-invasive BP assay system. Results are expressed as mean ± SD and the differences between groups were determined by analysis of variance (ANOVA) in which p 0.05 was considered significant. A summary of the results are demonstrated in figs1 and 2. Administration of CsA significantly (p 0.001) increased systolic BP from 113.87±8.5 to 136.2±7.27 (fig1) and heart rate from 330±11.29 to 429.5±27.23 (fig 2). However, the use of citrulline significantly (p 0.001) decreased the blood pressure to 102.28±3.85 (fig 1) and heart rate to 327.16±10.81 in cyclosporine-induced hypertension (fig 2). In addition, the use of citrulline in non-treated rats was associated with significant (p 0.007) reduction in blood pressure. While, arginine significantly (p 0.001) inhibited only the BP in CsA treated animals (fig 1).