Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of 1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine (alacepril, DU-1219) an antihypertensive compound with angiotensin converting enzyme inhibitory activity, and its metabolite, desacetyl-alacepril (DU-1227), on the cardiovascular and autonomic nervous systems and on the blood were compared with those of captopril in the experimental animals. Alacepril and DU-1227 at the i.v. dose of 10 mg/kg gradually lowered the diastolic blood pressure in pentobarbital anesthetized dogs. Captopril showed similar effects. However, the former two compounds showed triphasic effects on the carotid blood flow, i.e., transient increase immediately after the injection, second increase 2 min later, and gradual decrease 20-30 min later. The second increase by DU-1227 was more potent than that by alacepril. Alacepril, DU-1227 and captopril did not affect the pressor responses induced by norepinephrine in anesthetized cats. The contractions of the nictitating membrane in cats induced by electrical stimulation of the cervical sympathetic nerve or epinephrine were depressed with high doses of these three compounds. Captopril potentiated the contractions induced by bradykinin in isolated guinea-pig ileum, while alacepril and DU-1227 were without effect. These three compounds neither affected the resting tension of isolated ileum in guinea-pigs and rabbits nor the contractions induced by acetylcholine, histamine, serotonin and nicotine of isolated guinea-pig ileum. Alacepril at the oral dose of 60 mg/kg decreased the total acidity in pylorus ligated rats, and at higher doses depressed the intestinal charcoal meal passage in mice. Alacepril at comparatively low doses decreased the urine volume with slight reduction of Na+ and K+ excretions in saline-loaded rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:General pharmacology of the novel angiotensin converting enzyme inhibitor alacepril. 1st communication: Effects on cardiovascular, visceral and renal functions and on blood. 351 77

Hydralazine has been used widely to reduce tumor blood flow and thereby to induce hypoxia and to reduce extracellular pH (pHe) in tumors. Here we have investigated and compared the effects of the vasodilating drugs hydralazine, captopril, nifedipine, prazosin, sodium nitroprusside, and labetalol to reduce pHe in EMT-6 and KHT tumors of mice and to cause antitumor effects. After a single injection, captopril was most effective in reducing pHe in EMT-6 tumors with a decrease in mean pHe from 6.93 to 6.67 at 2 h after injection, while nifedipine was most effective for KHT tumors with a decrease in mean pHe from 6.96 to 6.75 at 1 h after injection. During 72 h of chronic administration into mice bearing tumors, nifedipine was ineffective in reducing pHe, but both captopril and hydralazine caused a small but significant reduction of pHe. Captopril caused significant delay in growth of the tumors, but had only a small effect on clonogenic cell survival. Captopril appears to be the most effective vasodilating drug to enhance tumor acidity.
 ...
PMID:The effects of vasodilating drugs on pH in tumors. 1056 16