RELATION OF PLASMA RENIN ACTIVITY TO THE ANTIHYPERTENSIVE EFFECT OF MK 421 IN THE RAT

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Abstract
The effect of the angiotensin converting enzyme inhibitor, MK 421 (N‐((S)‐1‐(ethoxycarbonyl)‐3‐phenylpropyl)‐l‐Ala‐l‐Pro), on the blood pressure of two‐kidney Goldblatt hypertensive rats has been investigated in relation to the initial plasma renin activity (PRA) and the initial blood pressure of the individual animals. Blood pressure was monitored by an indirect tail‐cuff method at 1, 3, 6 and 24 h after dosing. MK 421 produced a fall in blood pressure in the majority of animals, but the extent of this reduction varied considerably between individuals. The change in blood pressure showed a significant correlation with both the initial PRA and the initial blood pressures of the animals. However, only a modest correlation was found between the initial PRA and the degree of hypertension. MK 421 (10 mg/kg, orally) produced a mean blood pressure change which was statistically significant (P< 0.001) at all times tested. It is concluded that the degree of antihypertensive activity of MK 421 is related to the degree of activity of the renin‐angiotensin system which, in this model at least, is reflected by the PRA.