Long-term administration of L-arginine, L-NAME, and the exogenous NO donor molsidomine modulates urinary nitrate and cGMP excretion in rats.
OBJECTIVE
The effects of long term oral administration of L-arginine, NG-nitro-L-arginine methyl-ester (L-NAME), or molsidomine v placebo on blood pressure and the urinary excretion rates of NO3- and cyclic GMP were studied in Munich Wistar Frömter (MWF) rats.


METHODS
L-arginine (2 g.kg-1 body weight, n = 8), NG-nitro-L-arginine methylester (L-NAME; 5 mg.kg-1, n = 8), or molsidomine (3 mg.kg-1, n = 8) were given in drinking water and compared with placebo (n = 8) over a period of five months. Urinary excretion rates of NO3- (by gas chromatography) and cyclic GMP (by radioimmunoassay) were assessed in monthly intervals, as well as systolic blood pressure (tail plethysmography).


RESULTS
Mean basal blood pressure was 143.5(SEM 2.2) mm Hg. It was unaffected by L-arginine or molsidomine, but continuously and significantly increased during L-NAME treatment to 199.3(6.4) mm Hg (p < 0.05). Urinary excretion of NO3- increased by 20-41% v controls in L-arginine and molsidomine treated rats (p < 0.05), and decreased by 5-15% in L-NAME treated rats (p < 0.05). Urinary excretion of cyclic GMP increased by 9-38% v controls in the L-arginine and molsidomine treated groups and decreased by 5-20% in the L-NAME treated animals. Consistent with their higher blood pressure, L-NAME treated animals displayed cardiac hypertrophy.


CONCLUSIONS
Determination of urinary NO3- excretion by gas chromatography is a sensitive and specific method to assess NO formation in vivo. Long term oral administration of L-arginine in MWF rats increases NO production (as assessed by the urinary excretion rates of NO3- and cyclic GMP), but does not significantly influence systolic blood pressure, whereas L-NAME induces sustained hypertension and cardiac hypertrophy due to inhibition of NO formation.
Böger
R H
RH
Institute of Clinical Pharmacology, Hannover Medical School, Germany.
Bode-Böger
S M
SM
Gerecke
U
U
Frölich
J C
JC
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D002849:Chromatography, Gas; D006152:Cyclic GMP / Q000652:urine*; D006321:Heart / Q000033:anatomy & histology; D008297:Male; D008981:Molsidomine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester; D009566:Nitrates / Q000652:urine*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009566:Nitrates; D009569:Nitric Oxide; D001120:Arginine; D002784:Cholesterol; D008981:Molsidomine; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester