Quantitative evidence of peripheral conversion of angiotensin within the human leg: effects of local angiotensin-I administration and angiotensin-converting enzyme inhibition on regional blood flow and angiotensin-II balance across the leg.
The renin-angiotensin system relevantly contributes to the maintenance of systemic vascular tone and there is experimental evidence that large amounts of angiotensin-converting enzyme (ACE) are present in peripheral vascular tissues, including resistance vessels. To determine and quantify peripheral vascular conversion of angiotensin-I (ANG-I) to angiotensin-II (ANG-II) across the human leg, the response of regional blood flow to local regional intra-arterial infusion of ANG-I and change in associated ANG-II balance were evaluated during ANG-I infusion and following additional ACE inhibition. Ten sodium-loaded healthy men were enrolled in the study. Following cannulation of both femoral arteries and the right femoral vein, leg blood flow was determined (indocyanine-green dye-dilution method) at baseline conditions and during constant intra-arterial infusion of haemodynamically ineffective doses of ANG-I as well as following concomitant intra-arterial administration of low doses of the non-sulfhydril ACE inhibitor cilazapril. From the transfemoral arterio-venous differences in ANG-II plasma concentrations and the corresponding regional blood (plasma) flow, the ANG-II balance across the leg was calculated. Systemic blood pressure did not change throughout the trial, indicating that no major systemic effects were present during ANG-I infusion or concomitant ACE inhibition. Moreover, arterial ANG-II plasma concentrations were not significantly changed by ANG-I infusion. Leg blood flow decreased to below baseline values following ANG-I infusion, increasing again then in a dose-dependent manner during concomitant cilazapril administration. The calculated baseline ANG-II balance across the leg revealed a net extraction in 6 out of 10 subjects and a net ANG-II formation in 4.(ABSTRACT TRUNCATED AT 250 WORDS)
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I. Medizinische Universitätsklinik, Division of Clinical Pharmacology, Vienna, Austria.
Heinz
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Kleinbloesem
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D000328:Adult; D000803:Angiotensin I / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001711:Biotransformation; D001794:Blood Pressure / Q000187:drug effects; D017315:Cilazapril; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007208:Indocyanine Green; D007866:Leg / Q000098:blood supply*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D000804:Angiotensin II; D017315:Cilazapril; D000803:Angiotensin I; D007208:Indocyanine Green