Inhibitor of angiotensin I converting enzyme: (4R)-3-[(2S)-3-mercapto-2-methylpropanoyl]-4-thiazolidinecarboxylic acid (YS-980)
| Autor: | Sasaki Daizo, Yamamoto Kenjiro, Komori Tadamitsu, Funae Yoshihiko |
|---|---|
| Rok vydání: | 1980 |
| Předmět: |
medicine.medical_specialty
Angiotensin-Converting Enzyme Inhibitors Blood Pressure In Vitro Techniques Pentolinium Pentolinium Tartrate Biochemistry Plasma renin activity Norepinephrine (medication) Norepinephrine In vivo Internal medicine Renin Renin–angiotensin system medicine Animals Sulfhydryl Compounds 3-Mercaptopropionic Acid Pentobarbital Pharmacology Chemistry Angiotensin II Substrate (chemistry) Kinetics Thiazoles Endocrinology Thiazolidines Rabbits Angiotensin I Leucine medicine.drug |
| Zdroj: | Biochemical Pharmacology. 29:1543-1547 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/0006-2952(80)90606-1 |
| Popis: | Pharmacological studies on a new angiotensin I converting enzyme (ACE) inhibitor (4R)-3-[(2S)-3-mercapto-2-methylpropanoyl]-4-thiazolidinecarboxylic acid (YS-980), were carried out in vitro and in vivo . The activity of ACE prepared from rabbit lung by DEAE-Sepharose chromatography was determined using angiotensin I (Ang I) or hippuryl- l -histidyl- l -leucine (HHL) as a substrate. The concentrations of YS-980 producing 50 per cent inhibition of ACE activity (ID 50 ) when HHL or Ang I was used as a substrate were 9.5 and 13 nM, respectively. The mode of inhibition was competitive, with a K i of 6 nM. Renin activity was not affected by YS-980. Arterial blood pressure was decreased slightly by intravenous injection of YS-980 (0.1 or 1.0mg/kg) to anesthetized rats with or without pretreatment with pentolinium. Pretreatment with YS-980 suppressed the pressor response to Ang I but not to norepinephrine. Intravenous injection of YS-980 (1mg/kg) caused a 21 per cent increase in the pressor response to angiotensin II. These results indicate that YS-980 is a potent and specific inhibitor of ACE. |
| Databáze: | OpenAIRE |
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