Effect of oral L-arginine administration for three weeks in two kidney-two clip hypertensive rats.
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(-6) M, p<0.05 and 10(-5)M, 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 (TxA(2)) - 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 (PGI(2)) 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 PGI(2) synthesis under PDBu stimulation. 3) greater PKC activation and TxA(2) production rather than lower NO availability might result in systemic hypertension in 2K-2C rats.
Departamento de Ciencias Fisiológicas, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. idelariv@fmed.uba.ar
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de la Riva
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Rosón
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Vega
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Albornoz
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Palumbo
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Ferrero
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Damiano
D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D011464:Epoprostenol / Q000096:biosynthesis / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy; D007552:Isotonic Solutions / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis; D013997:Time Factors
D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D009566:Nitrates; D009573:Nitrites; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D013929:Thromboxane B2; D011189:Potassium Chloride; D001120:Arginine; D011464:Epoprostenol; D011493:Protein Kinase C; D000109:Acetylcholine