Budralazine was evaluated for its protective effect on the onset of cerebrovascular lesions in SHR given 1.5% NaCl as
drinking water. The
salt-loading for 67 days rapidly accelerated the development of
hypertension in SHR (from 180 to over 250 mmHg, 40 days after the loading). The acceleration of
hypertension was accompanied by an increase in the incidence of brain softening,
cerebral infarct, angionecrosis and
hemorrhage by 30-60% following the
thrombosis and
necrosis of cerebral arterioles. Renal angionecrosis associated with the interstitial
nephrosis was also observed by 90% in the animals. Throughout the
salt-loading period,
oral administration of
budralazine (1, 4 and 15 mg/kg/day) resulted in a dose-dependent inhibition of the accelerated
hypertension. At larger doses (4 and 15 mg/kg/day),
budralazine almost completely ameliorated the cerebral and renal lesions and significantly attenuated the rise of weight in the brain and heart observed in the
salt-loaded control rats. Changes in the serum biochemical findings were also inhibited by this
drug. In some of the parameters measured,
budralazine appeared to be more efficacious than
hydralazine (1, 4 and 15 mg/kg/day, p.o.). These results suggest that
budralazine attenuates the serious development of
hypertension and reduces the incidence and severity of
stroke in
salt-loaded SHR.