L-arginine partially reverses established adrenocorticotrophin-induced hypertension and nitric oxide deficiency in the rat.
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).


CONCLUSIONS
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.
Wen
C
C
Department of Medicine, The St. George Hospital, University of New South Wales, Sydney, Australia.
Li
M
M
Fraser
T
T
Wang
J
J
Turner
S W
SW
Whitworth
J A
JA
D000324:Adrenocorticotropic Hormone / Q000633:toxicity*; D000596:Amino Acids / Q000097:blood; D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002956:Citrulline / Q000097:blood; D006152:Cyclic GMP / Q000652:urine; D004341:Drug Evaluation; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000172:deficiency*; D009573:Nitrites / Q000097:blood / Q000652:urine; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D000596:Amino Acids; D009566:Nitrates; D009573:Nitrites; D002956:Citrulline; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D001120:Arginine; D006152:Cyclic GMP