[Effects of single and repeated oral administration of MK-421 and captopril on blood pressures in normotensive and experimental hypertensive rats].
In the single dose study, the aortic blood pressure in conscious normotensive rats, 2-kidney, 1-clip renal hypertensive rats (2K-RHR), 1-kidney, 1-clip renal hypertensive rats (1K-RHR) or DOCA hypertensive rats was measured for 24 hr after the oral administration of angiotensin converting enzyme (ACE) inhibitors such as MK-421 or captopril. MK-421 at 3 mg/kg and captopril at 10 mg/kg markedly lowered the blood pressure of 2K-RHR. MK-421 at 10 mg/kg and captopril at 30 mg/kg only modestly lowered the blood pressure of 1K-RHR. In contrast, both ACE inhibitors failed to reduce blood pressure in DOCA and normotensive rats. In the repeated dose study, the systolic blood pressures in normotensive rats, 2K-RHR or spontaneously hypertensive rats (SHR) were measured twice a week for 3 weeks treatment of either MK-421 at 3 mg/kg or captopril at 10 mg/kg. Both ACE inhibitors produced significant antihypertensive effects in these model rats, and the effects were sustained throughout the treatment period. The antihypertensive effects in 2K-RHR were greater than those in SHR and normotensive rats. These results indicate that MK-421 and captopril cause the most significant antihypertensive effect in 2K-RHR in which the renin-angiotensin system played a dominant role in blood pressure regulation. The antihypertensive effect of MK-421 was approximately 3 times as potent as that of captopril in these hypertensive models.
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D003900:Desoxycorticosterone / Q000037:antagonists & inhibitors; D004656:Enalapril / Q000627:therapeutic use*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D006977:Hypertension, Renal / Q000188:drug therapy; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains
D000959:Antihypertensive Agents; D003900:Desoxycorticosterone; D004656:Enalapril; D002216:Captopril