YH-200

1. The depressor response to sodium nitroprusside (SNP) and the pressor response to Nω‐nitro‐L‐arginine methyl ester (L‐NAME) were investigated in anaesthetized and ganglion‐blocked 6 week old (young) and 20 week old (adult) spontaneously hypertensive rats (SHR), and the results were compared with those in age‐matched normotensive Wistar‐Kyoto (WKY) rats.2. SNP produced a dose‐dependent decrease of the mean blood pressure (BP) in both strains, and no differences in vascular sensitivity to SNP were observed between the strains.3. L‐NAME caused dose‐dependent pressor responses in both strains. The sensitivity and the maximal response to L‐NAME in SHR were significantly greater than those in age‐matched WKY (P < 0.05 or 0.01; t‐test, 13d.f. in both ages). However, there were no significant differences in the responses between ages in each strain.4. Acute reduction of BP induced by 7‐O‐ethylfangchinoline did not affect the responses to SNP and L‐NAME in the adult SHR.5. These results indicate that a greater amount of NO is tonically released in SHR and that its contribution to BP control is greater in SHR than in WKY, whereas vascular sensitivity to NO does not differ between the strains. In addition, acute changes in BP do not affect the degree of dependency on NO for BP control.

1. The antihypertensive effects of 10 mg/kg trichloromethiazide (TCM), 10 mg/kg 7–O‐ethylfangchinoline (7–O‐EFC) and the combination of these drugs given orally once daily for 2 weeks were investigated by measuring the blood pressure (BP), heart rate (HR) and activity in conscious, freely moving spontaneously hypertensive rats (SHR) fitted with a telemetry device.2. Clear diurnal rhythms of the HR and activity in synchrony with the light/dark cycle were observed during therapy, whereas the BP rhythm was obscure.3. Alone, TCM and 7–O‐EFC produced slight and insignificant reductions of 24 h mean BP, whereas in combination they produced an additive and significant BP reduction, compared with the vehicle‐treated controls, from the third day of therapy. The BP reduction induced by the combination of these drugs during the dark phase was more marked than that during the light phase.4. None of the drug therapies affected the HR and activity diurnal rhythms.5. The results of the present study demonstrate that the telemetry method is useful for monitoring the antihypertensive effects of drugs in SHR under physiological conditions with minimal stress.