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  • Title: Tissue angiotensin-converting enzyme blockade by MC-838 (altiopril calcium) infused intravenously to miniature pigs: comparison with captopril.
    Author: Sakai K, Shiraki Y, Akima M, Imagawa J, Hinohara Y, Koga T, Ichihara T, Tohira Y.
    Journal: Arch Int Pharmacodyn Ther; 1988; 294():228-40. PubMed ID: 2852930.
    Abstract:
    The effect of a new orally active angiotensin-converting enzyme (ACE) inhibitor, calcium(-)-N-[(S)-3-[(N-cyclohexyl-carbonyl-D-alanyl)thio]-2-methyl- prolinate (MC-838, altiopril calcium), on cardiohemodynamics and tissue ACE activity was compared with that of captopril in the anesthetized miniature pig. MC-838 and captopril were infused i.v. for 1 or 3 hr at an equimolar rate of 20 and 10 micrograms/kg.hr-1, respectively. When MC-838 was infused i.v., captopril appeared in approximately 40% of MC-838 in serum, indicating that the amount of serum captopril during the equimolar concentration treatment with MC-838 corresponds to half of serum captopril after the dosing of captopril. During the infusion, the drugs did not significantly affect systemic blood pressure (SBP), heart rate (HR), renal blood flow (RBF) and renal vascular resistance (RVR). MC-838 and captopril, in a similar degree, attenuated the vasoconstrictor response to angiotensin-I (A-I) injected into the renal artery (i.a.), and enhanced the vasodilator one to i.a. bradykinin, 3 hr after the onset of the drug infusion. The animals were sacrificed at 1 and 3 hr after the onset of the infusion of MC-838 or captopril, and the ACE activity in serum and some target organs (lung, kidney, heart, brain and aorta) was determined. Effective activities of MC-838 and captopril occurred in the lung and kidney (only at 3 hr for captopril) where higher ACE activity in a variety of tissues was found, to a lesser degree in the serum (only by captopril) and not at all in the brain, heart and aorta.
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