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Notes: This study was designed to compare the activity of three structurally different drugs (SQ 14 225, SA 446, and MK 421) as inhibitors of angiotensin converting enzyme in vivo and to compare their effects in two experimental models of hypertension.2 MK 421 was less effective than SA 446 or SQ 14 225 in suppressing the pressor responses to intravenous angiotensin I 3 min after the administration of low doses of the converting enzyme inhibitors (CEIs) but more effective than SA 446 or SQ 14 225 30 min or longer after doses of CEIs ranging from 25 to 2500 nmol/kg i.v.3 The CEIs administered at 8 μmol/kg intravenously blocked the pressor response to angiotensin I (AI) to a similar maximal effect but the time for recovery was much slower for MK 421 than for SQ 14 225 or SA 446. After oral administration (15 mg/kg) prolonged blockade was observed with each of the three drugs although some recovery occurred with SA 446 after 5 h. The effect of a small dose of MK 421 intravenously (0.4 μmol/kg) was more prolonged in anaesthetized than in conscious spontaneously hypertensive rats (SHR).4 Anaesthetized adult SHR showed slow progressive falls of blood pressure after 8 /unol/kg of each drug intravenously although the effect of SA 446 was less than for SQ 14 225 or MK 421 which were equipotent. After acute oral administration of each CEI at 80 μmol/kg, conscious SHR showed significant falls in blood pressure but the effect of SA 446 was less than the other two inhibitors which appeared equipotent.6 After chronic oral administration of the drugs to conscious SHR, SA 446 (80 μmol/kg per day) did not alter blood pressure although SQ 14 225 was effective at this dose. At a higher dose of 160 /μmol/kg per day SA 446 significantly lowered blood pressure of SHR in a manner similar to the same dose of SQ 14 225 or MK 421.7. We conclude that the three drugs are potent, orally effective converting enzyme inhibitors. The duration of action was in the order MK 421 〉SQ 14 225 〉SA 446. MK 421 appears the most potent due to both a higher affinity for converting enzyme in vitro and a longer persistence of action in vivo. In renal hypertension, the drugs appeared equipotent but in the SHR at low doses, SA 446 was ineffective.