Local inhibition of converting enzyme and vascular responses to angiotensin and bradykinin in the human forearm.

Abstract

SUMMARY1. 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.

Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin

“…This dose blocks conversion of Ang I to Ang II and potentiates the vasodilator effect of BK in the forearm. 20 During enalaprilat, baseline measurements and infusions of MCh and BK were repeated. Three subjects complained of headache during MCh infusion.…”

Gradual reactivation of vascular angiotensin I to angiotensin II conversion during chronic ACE inhibitor therapy in patients with diabetes mellitus

“…This is a well-established technique based on the premise that AI only produces vasoconstriction when converted into AII in vascular tissue [9]. There are two reasons why this technique is thought to mainly reflect AI to AII conversion in vascular tissue, rather than within the circulation [11]. The first reason is that AI to AII conversion in blood is much slower than the transit time in the circulation.…”

Angiotensin converting enzyme inhibition does not affect the response to exogenous angiotensin II in the human forearm.

“…An estimate of between subject variability was obtained from analysis of data from a previous study [17]. It was assumed that the within subject crossover design would reduce the variance by a factor of two [18].…”