Comparison of the time course of action of captopril on angiotensin-converting enzyme with the time course of its antihypertensive effect.
The effects of captopril on blood pressure and plasma angiotensin-converting enzyme were studied in cats with two-kidney, one-clip experimental hypertension. The time period for the return of blood pressure to predrug values was observed to be many days longer than the recovery time of enzyme activity. The possibility that the discrepancy might be due to a differential effect of captopril on the pulmonary and vessel wall plasma membrane enzymes as opposed to the circulating plasma enzyme, all of which act on blood-borne angiotensin I, was studied in an anesthetized bioassay cat preparation employing two routes of drug administration. No large disparity between captopril inhibition of the different enzyme systems was noted. It is concluded that the discrepancy between the inhibition of the plasma enzyme and the antihypertensive effect of the drug might result from: (a) a nonspecific return of the disease process that might be predicted to occur with other antihypertensive agents: the "slow pressor" actions of angiotensin are discussed in relationship to this hypothesis; (b) an inhibition of converting enzyme at a localized site, such as the media of the vessel wall or certain brain areas, where the enzyme might not act on blood-borne angiotensin I; and (c) a direct vasodilatory action unrelated to the renin-angiotensin system.
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D002415:Cats; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D007700:Kinetics; D011392:Proline / Q000031:analogs & derivatives*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D011392:Proline; D002216:Captopril