Contribution of splanchnic and peripheral vascular tissues to the disposal of angiotensin-II and to regional conversion rates of angiotensin-I: a pilot study in humans.
The present study investigates angiotensin-II (A-II) balance across the splanchnic vascular bed and leg vascular tissues in humans, at baseline conditions and following a systemically ineffective femoral arterial angiotensin-I (A-I) infusion, both before and during inhibition of angiotensin-converting enzyme (ACE) with enalaprilat. In six healthy men, net regional A-II balance was calculated from the transfemoral or transsplanchnic arteriovenous differences in plasma concentrations and the corresponding regional plasma flow. Systemic and splanchnic hemodynamics remained unchanged throughout the trial, indicating an absence of major hemodynamic effects during A-I infusion or concomitant ACE inhibition. In contrast, regional leg plasma flow significantly decreased following A-I infusion (165.2 +/- 15.7 vs. 304.7 +/- 43.7; p less than 0.01) and again gradually returned to about baseline values after ACE inhibition. Baseline net transfemoral A-II balance was equilibrated at slight formation rates in four subjects and at minimal extraction rates in two of the six subjects. Following A-I infusion, a shift toward net femoral A-II formation (average increase 2,774% above baseline) was observed in all subjects (p less than 0.01). After concomitant ACE inhibition, femoral A-II balance again returned to baseline levels. Across the splanchnic vascular bed a net baseline. A-II extraction was observed in all subjects. Following A-I infusion an average increase by 285% (p less than 0.05) in splanchnic A-II extraction was observed. During concomitant ACE inhibition splanchnic A-II extraction tended to decrease toward baseline values in four subjects, and remained rather unchanged in two subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Gasic
S
S
I. Medizinische Universitätsklinik, Division of Clinical Pharmacology, Vienna, Austria.
Kleinbloesem
C H
CH
Heinz
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G
Waldhäusl
W
W
D000328:Adult; D000803:Angiotensin I / Q000008:administration & dosage / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001711:Biotransformation; D001794:Blood Pressure / Q000187:drug effects; D015773:Enalaprilat / Q000494:pharmacology; D005269:Femur / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007208:Indocyanine Green; D007269:Injections, Intra-Arterial; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D012039:Regional Blood Flow / Q000502:physiology*; D013152:Splanchnic Circulation / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D015773:Enalaprilat; D007208:Indocyanine Green