Pharmacology of converting enzyme inhibitors: new aspects.
The antihypertensive mechanism of CEI cannot be solely explained by an inhibition of the plasma RAS with reduced vasoconstrictor action of circulating ANG II. Inhibition of Kininase II with an increase of endogenous bradykinin does not appear to play a major role. Within the dose range used therapeutically, captopril and other CEI inhibit the facilitatory action of ANG II on neurogenic vasoconstriction, leading to a reduced sympathetic tone. CEI may also interfere with sympathetic reflexes. Doses above the therapeutic range seem to inhibit the sympathetic nervous system through mechanisms unrelated to CE inhibition. A reduced local generation of ANG II within tissues such as vascular wall, kidney or brain appears to contribute sympathetic tone. The type of hypertension (e.g. with or without stimulated plasma RAS or sympathetic tone) and the chemical characteristics of the CEI used (e.g. lipid solubility governing penetration into tissues) may determine the relative importance of the different mechanisms and sites of action for the reduction of blood pressure.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects; D013045:Species Specificity; D013116:Spinal Cord / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002216:Captopril; D007703:Peptidyl-Dipeptidase A