Local inhibition of converting enzyme and vascular responses to angiotensin and bradykinin in the human forearm.
1. The function of angiotensin converting enzyme was investigated in twenty-four healthy men. Forearm blood flow was measured under basal conditions and during administration of enalaprilat (a converting enzyme inhibitor) and/or peptide substrates of converting enzyme into the left brachial artery. Blood flow was compared in the two arms. 2. Enalaprilat had no effect on basal blood flow. The concentration of enalaprilat in venous blood from the control arm was low, and plasma renin activity was not increased, indicating that systemic inhibition of converting enzyme did not occur. 3. Effects of angiotensin and of bradykinin, administered intra-arterially, were limited to the infused arm. Enalaprilat (13 nmol min-1) inhibited converting enzyme in the infused arm, in which it caused approximately a 100-fold reduction in sensitivity to angiotensin I, while having no effect on the vasoconstriction caused by angiotensin II. Enalaprilat increased vasodilatation caused by bradykinin. 4. Aspirin, an inhibitor of cyclo-oxygenase, did not inhibit vasodilatation caused by bradykinin whether infused alone or with enalaprilat, indicating that these responses are not mediated by prostaglandins. 5. We conclude that under basal conditions neither conversion of angiotensin I to angiotensin II nor degradation of bradykinin determines resistance vessel tone in the human forearm. Converting enzyme may affect vascular tone in situations in which intravascular concentrations of peptides are increased over those present under basal conditions.
Benjamin
N
N
Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London.
Cockcroft
J R
JR
Collier
J G
JG
Dollery
C T
CT
Ritter
J M
JM
Webb
D J
DJ
D000328:Adult; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001775:Blood Circulation / Q000187:drug effects*; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D015773:Enalaprilat / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D015773:Enalaprilat; D001920:Bradykinin