C. Wen et al., L-arginine partially reverses established adrenocorticotrophin-induced hypertension and nitric oxide deficiency in the rat, BLOOD PRESS, 9(5), 2000, pp. 298-304
Background: L-arginine treatment prevents adrenocorticotrophin (ACTH) induc
ed hypertension in the rat. This study examined whether L-arginine treatmen
t could reverse established ACTH hypertension and its effects on markers of
decreased NO activity. Methods: Sixty-four male Sprague-Dawley rats were r
andomly divided into 6 groups given 12 days of treatment: (1) sham (0.9% Na
Cl, 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 bl
ood pressure, water intake, urine volume, and body weight were measured eve
ry second day. At the end of the experiments, plasma and urinary nitrate/ni
trite (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 +/- I to 1
47 +/- 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 +/- I mmHg on day 12, n = 10, p < 0.001). In contrast, D-argi
nine did not affect blood pressure in ACTH-treated rats (group 6). ACTH inc
reased water intake and urine volume and decreased body weight, and L-argin
ine administration did not alter these parameters. ACTH decreased plasma ci
trulline (group 1 vs 2: 115 +/- 7 vs 67 +/- 6 mu M/L, n = 16, p < 0.001) an
d NOx concentrations (group 1 vs 2: 8.3 +/- 0.8 vs 4.5 +/- 0.6 <mu> M/L, n
= 10, p < 0.001) and these decreases were reversed by L-arginine treatment
(group 4: citrulline 98 +/- 9 <mu> M/L, NOx 9.1 +/- 1.6 mu 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
: Supple mentation with L-arginine partly reversed established ACTH-induced
hypertension and restored plasma NOx and citrulline concentrations to leve
ls seen in sham-treated rats. These data are consistent with previous studi
es suggesting that functional NO deficiency has a role in ACTH-induced hype
rtension in rats.