Cardiovascular effects of a new potent dopamine beta-hydroxylase inhibitor in spontaneously hypertensive rats.

摘要: The cardiovascular effects of a new class potent inhibitors dopamine beta-hydroxylase (DBH) were evaluated in spontaneously hypertensive rats (SHR). SK&F 102698 [1-(3,5-difluorobenzyl)imidazole-2-thiol] is the prototype molecule this substituted 1-benzylimidazole-2-thiols and one most DBH yet described. After acute p.o. administration conscious unrestrained SHR, elicited dose-dependent decrease mean arterial blood pressure. antihypertensive effect was marked by gradual onset with long duration activity. produced accompanied bradycardia. inhibited vivo as demonstrated its ability to increase vascular levels (DA) while concomitantly decreasing norepinephrine (NE), thus increasing overall DA/NE ratio. chronic developing SHR. SHR administered once daily for 9 weeks beginning when animals 4 age. (50 mg/kg) significantly attenuated development hypertension these Tolerance inhibition not observed pressures drug-treated still reduced 20 hr after drug administration. Vascular catecholamine determined mesenteric artery chronically treated animals. DA increased 290%, NE decreased 36% ratio 520%, compared controls. Furthermore, hearts weights receiving approximately 10% lower than present study demonstrates that an effective whose are mediated novel mechanism inhibition.