Effects of L‐arginine Supplementation on the Tissue Production of Nitric Oxide and Cardiovascular Modulation by the Paraventricular Nucleus of Hypothalamus

Abstract

L‐Arginine is the substrate for nitric oxide (NO) synthesis and in the paraventricular nucleus of the hypothalamus (PVN) NO plays an important role in cardiovascular function. The objective of this study was to evaluate the effects of L‐arginine supplementation on cardiovascular responses by PVN and NO production. Wistar rats were used (220–250g) randomly divided into two groups: control (C) or L‐arginine (LA). The supplementation with L‐arginine was conducted in the LA group (62.5 mg/mL/rat/day), by oral gavage, and Group C received water (1 mL) for 4 weeks, 5times/week. Then the animals underwent to guide cannulas implantation to the PVN and artery and femoral vein catheterization. The baseline parameters of mean arterial pressure (MAP) and heart rate (HR) were recorded 24 hours after catheterization and held bilateral administration of 0.9% saline or an nNOS inhibitor (n‐Propyl‐L‐Arginine, 4nmol/100NL) in the PVN. We collected heart, kidneys, thoracic aorta, and punchs of the PVN for nitrite dosages by Cadmium‐Griess method. Spectral analysis was performed by the software Cardio Series (version 2.4). The supplementation with L‐arginine caused resting bradycardia (C: 359 ± 6 vs. LA: 335 ± 6 b/min) without change in MAP, as well as greater pressor response (ΔPAM: C: 17 ± 2 vs. LA: 26 ± 3 mmHg) and tachycardia (ΔFC: C: 86 ± 6 vs. LA: 129 ± 13 b/min) to n‐propyl in the PVN. At baseline the spectral analysis of rats of LA group showed: lower sympathetic modulation for systolic blood pressure (LF: C: 4.6 ± 0.6 vs. LA: 2.1 ± 0.4 mmHg2) smaller variance in pulse interval (C: 42.4 ± 3.2 vs. LA: 24.6 ± 5.1 ms2), lower sympathovagal index (LF/HF: C: 0.8 ± 0.1 vs. LA: 0.3 ± 12:07) and increase of spontaneous baroreflex gain: (Gain full baroreflex: C: 1.3 ± 0.1 vs. LA: 2.2 ± 0.2 ms/mm Hg; Gain Up: C: 1.4 ± 0.1 vs. LA: 2.5 ± 0.3 ms/mm Hg; Gain Down: C: 1.2 ± 0.1 vs. LA: 1.8 ± 0.2 ms/mmHg). In addition, LA animals showed higher concentrations of nitrite in the PVN (C: 3.3 ± 0.7 vs. LA: 5.5 ± 0.7 uM/mg/PVN), kidneys (C: 7 ± 1 vs. LA: 18 ± 3 uM) and thoracic aorta (C: 4 ± 0.6; LA: 12 ± 3 .mu.M). Therefore, supplementation with L‐arginine modified the baseline autonomic control, increase in nitregirc tonus by NO in the PVN via nNOS, and an increase in NO bioavailability, leading to similar effects obtain after exercise training.Support or Funding InformationCNPq (fellowship program)