BACKGROUND: L-arginine treatment prevents adrenocorticotrophin (ACTH) induced hypertension in the rat. This study examined whether L-arginine treatment could reverse established ACTH hypertension and its effects on markers of decreased NO activity. METHODS: Sixty-four male Sprague-Dawley rats were randomly divided into 6 groups given 12 days of treatment: (1) sham (0.9% NaCl, 0.5 ml/kg, subcutaneously, sc, n = 16); (2) ACTH (0.5 mg/kg/day, sc, n = 16); (3) sham + L-arginine (0.6% in food, from treatment day 8 onwards, n = 10); (4) ACTH + L-arginine (n = 10); (5) sham + D-arginine (0.6% in food, from T 8 onwards) (n = 6); and (6) ACTH + D-arginine (n = 6). Systolic blood pressure, water intake, urine volume, and body weight were measured every second day. At the end of the experiments, plasma and urinary nitrate/nitrite (NOx), plasma amino acid concentrations (in groups 1-4), and urinary cyclic guanosine monophosphate (cGMP) concentrations were measured. RESULTS: Sham, sham + L-arginine, and sham + D-arginine treatments did not affect blood pressure. ACTH increased systolic blood pressure (from 121 +/- 1 to 147 +/- 2 mmHg, p < 0.001, pooled control vs treatment day 12, mean +/- sem), and this was partially reversed by L-arginine (group 4: from 141 +/- 2 on day 8 to 133 +/- 1 mmHg on day 12, n = 10, p < 0.001). In contrast, D-arginine did not affect blood pressure in ACTH-treated rats (group 6). ACTH increased water intake and urine volume and decreased body weight, and L-arginine administration did not alter these parameters. ACTH decreased plasma citrulline (group 1 vs 2: 115 +/- 7 vs 67 +/- 6 micro M/L, n = 16, p < 0.001) and NOx concentrations (group 1 vs 2: 8.3 +/- 0.8 vs 4.5 +/- 0.6 microM/L, n= 10, p < 0.001) and these decreases were reversed by L-arginine treatment (group 4: citrulline 98 +/- 9 micro M/L, NOx 9.1 +/- 1.6 micro M/L, group 2 vs 4, both p < 0.05). ACTH produced marked increases in urinary cGMP excretion (group 1 vs 2: 0.5 +/- 0.1 vs 1.9 +/- 0.4 nmol/24 h, p < 0.01). CONCLUSION: Supplementation with L-arginine partly reversed established ACTH-induced hypertension and restored plasma NOx and citrulline concentrations to levels seen in sham-treated rats. These data are consistent with previous studies suggesting that functional NO deficiency has a role in ACTH-induced hypertension in rats.
BACKGROUND:L-arginine treatment prevents adrenocorticotrophin (ACTH) induced hypertension in the rat. This study examined whether L-arginine treatment could reverse established ACTH hypertension and its effects on markers of decreased NO activity. METHODS: Sixty-four male Sprague-Dawley rats were randomly divided into 6 groups given 12 days of treatment: (1) sham (0.9% NaCl, 0.5 ml/kg, subcutaneously, sc, n = 16); (2) ACTH (0.5 mg/kg/day, sc, n = 16); (3) sham + L-arginine (0.6% in food, from treatment day 8 onwards, n = 10); (4) ACTH + L-arginine (n = 10); (5) sham + D-arginine (0.6% in food, from T 8 onwards) (n = 6); and (6) ACTH + D-arginine (n = 6). Systolic blood pressure, water intake, urine volume, and body weight were measured every second day. At the end of the experiments, plasma and urinary nitrate/nitrite (NOx), plasma amino acid concentrations (in groups 1-4), and urinary cyclic guanosine monophosphate (cGMP) concentrations were measured. RESULTS: Sham, sham + L-arginine, and sham + D-arginine treatments did not affect blood pressure. ACTH increased systolic blood pressure (from 121 +/- 1 to 147 +/- 2 mmHg, p < 0.001, pooled control vs treatment day 12, mean +/- sem), and this was partially reversed by L-arginine (group 4: from 141 +/- 2 on day 8 to 133 +/- 1 mmHg on day 12, n = 10, p < 0.001). In contrast, D-arginine did not affect blood pressure in ACTH-treated rats (group 6). ACTH increased water intake and urine volume and decreased body weight, and L-arginine administration did not alter these parameters. ACTH decreased plasma citrulline (group 1 vs 2: 115 +/- 7 vs 67 +/- 6 micro M/L, n = 16, p < 0.001) and NOx concentrations (group 1 vs 2: 8.3 +/- 0.8 vs 4.5 +/- 0.6 microM/L, n= 10, p < 0.001) and these decreases were reversed by L-arginine treatment (group 4: citrulline 98 +/- 9 micro M/L, NOx 9.1 +/- 1.6 micro M/L, group 2 vs 4, both p < 0.05). ACTH produced marked increases in urinary cGMP excretion (group 1 vs 2: 0.5 +/- 0.1 vs 1.9 +/- 0.4 nmol/24 h, p < 0.01). CONCLUSION: Supplementation with L-arginine partly reversed established ACTH-induced hypertension and restored plasma NOx and citrulline concentrations to levels seen in sham-treated rats. These data are consistent with previous studies suggesting that functional NO deficiency has a role in ACTH-induced hypertension in rats.