高血圧症例におけるBenzothiazepine誘導体(CRD-401)の降圧・腎血流量増加・Na利尿作用

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1. Animal studies: d-cis-isomer of benzothiazepine derivative (CRD-401), which exerts a strong coronary vasodilating effect, was confirmed to have weak or almost no hypotensive effect in the anesthetized normal dog. However, when administered to the hypertensive dog induced by intravenous infusion ot angiotensin II, CRD-401 caused prominent decrease of diastolic blood pressure and restoration of renal blood flow accompanied by remarkable sodium diuresis. The effect was nonspecific since vasoconstricting responses to injected norepinephrine and stimulation of mesenteric nerves were also inhibited in dogs in which mesenteric vessels were perfused in vivo. Phentolamine inhibited dose-dependently response to norepinephrine, but CRD-401 did not. The experiments suggest that CRD-401 has direct action on vascular smooth muscle and cannot readily be classified into alpha or beta adrenergic blocking drugs. 2. Clinical studies: CRD-401 was investigated by oral administration of 60~90 mg per day in 26 patients with hypertension 'lssociated with renal parenchymal disease and renovascular hypertension. Blood pressure was lowered in two thirds of the patients. Within 2 to 4 days after the administration, blood pressure was reached the lowest level and then gradually returned to the control levels after several weeks. Urinary sodium excretion was remarkably increased, and urine volume also increased but at less extent. The changes were transient similarly to that of blood pressure. I-131-Hippuran clearance was elevated, although statistically not significant. Endogenous creatinine clearance did not change immediately after the administration, but in some patients there was transient increase and in others there was gradual increase. These renal functional changes were also observed in those patients whose blood pressure was not lowered. Preliminary results with oral administration suggest that CRD-401 would be a useful therapeutic agent, but the optimum dosage and indications for use of this drug remain to be determined.
泌尿器科紀要刊行会の論文
1972-09-00

著者

桜井勗
大阪厚生年金

高血圧症例におけるBenzothiazepine誘導体(CRD-401)の降圧・腎血流量増加・Na利尿作用

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