Effect of Oral L-Arginine Administration for Three Weeks in Two Kidney-two Clip Hypertensive Rats

Abstract

Nitric oxide (NO) has been identified as an effective vascular relaxant. This study analyses the contribution of the precursor L-arginine (L-arg) by oral administration in two kidney-two clip hypertension in the rat (2K-2C). Two groups were studied: sham (SH, n = 21) and hypertensive (HT, n = 15). After 4 weeks of surgery, a group of rats remained as controls (SHc and HTc, respectively), while others were supplemented with L-arg (1.25 g/L) in drinking water (SHa and HTa) for 3 weeks. Blood pressure was significantly increased in 2K-2C rats but remained unchanged after L-arg treatment. Plasma nitrite/nitrate concentrations were not different among groups. The contractile response of aorta to KCl, serotonin and the protein kinase C (PKC) stimulant, phorbol 12,13-dibutyrate (PDBu) was also evaluated. Higher contractile responses to PDBu (p < 0.001) and lower relaxation to acetylcholine (Ach 10⁻⁶M, p < 0.05 and 10⁻⁵M, p < 0.02) were observed in aortic rings of HTc vs SHc; L-arg supplementation significantly diminished tension development to all agonists (p < 0.05) but failed to modify the lower relaxation to Ach in HTa. Thromboxane (TxA₂) – synthesis in rings of HTc was higher than in SHc under basal conditions (p < 0.05). In the groups with supplement of L-arg, PDBu significantly stimulated prostacyclin (PGI₂) synthesis more in HTa rats than in SHa ones (p < 0.05). To conclude: 1) L-arg fails to modify hypertension development in 2K-2C rats; and 2) L-arg exerts a beneficial effect on the vascular wall, by reducing contractility in rings from HTa rats; it also improved PGI₂ synthesis under PDBu stimulation. 3) greater PKC activation and TxA₂ production rather than lower NO availability might result in systemic hypertension in 2K-2C rats.