When the potent inhibitor of nitric oxide (NO) synthesis N-G-nitro-L-argini
ne (L-NNA) was incorporated into the diet, hypertension was induced and sus
tained due to the effects of the long-term inhibition of endothelium-depend
ent relaxing factor (EDRF)/NO. The effects of L-NNA on normotensive rats of
four strains (Donryu, Sprague-Dawley (SD), Wistar, and Wistar-Kyoto (WKY))
were compared relative to control rats. L-NNA administration caused a shar
p initial increase in systolic blood pressure (SBP) at 2 weeks in all anima
ls, and this was followed by a gradual and steady increase until 4 weeks. A
t the end of the experiments (5 weeks), the mean SEP of Donryu and SD rats
was decreased. The maximum blood pressure of Donryu and Wistar rats during
the experiments exceeded 200 mmHg, but that of SD and WKY rats was below 20
0 mmHg. Body weight loss and death were observed only in L-NNA-fed Donryu r
ats. Pathological changes in the kidneys and the morbidity rates for the le
sions were determined, and indicated that the Donryu L-NNA group was 100% p
ositive. These results suggest that the Donryu strain is more sensitive to
L-NNA than the other strains. That dietary L-NNA-induced hypertension in no
rmotensive rats of the four strains provides a new artificially-induced hyp
ertensive model in which vasoconstriction occurs mainly due to EDRF deficie
ncy.