[Systemic and regional hemodynamic effects of a new angiotensin converting enzyme and neutral endopeptidase mixed inhibitor, alatriopril, in the dog].
Alatriopril is a dual inhibitor of two cell surface metallopeptidases which play important roles in the regulation of arterial blood pressure and renal function: the angiotensin I converting enzyme (ACE) which catalyses transformation of angiotensin I to angiotensin II, and the neutral endopeptidase (NEP; EC 3.4.24.11; atriopeptidase), responsible for the degradation of the atrial natriuretic factor (ANF). The purpose of the present study was to evaluate the systemic and regional hemodynamic effects of alatrioprilat, the active part of alatriopril, in 6 anesthetized, closed-chest beagle dogs instrumented for the measurement of arterial pressure (aortic catheter), cardiac output (thermodilution), as well as femoral and renal artery flows (Doppler). Animal received alatrioprilat at the doses of 1 and 10 mg/kg (i.v. bolus). Hemodynamic parameters were measured at baseline, then 15, 30, 45 and 60 min after administration of each dose. In addition, plasma ANF and ACE activity were determined at baseline and 30 min after administration. At the dose of 1 mg/kg, alatrioprilat dit not induce marked hemodynamic effects, except a transient hypotension which appeared within the first 10 min after administration and lasted less than 10 min. Neither plasma ANF nor angiotensin converting enzyme activity were affected by this dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Richard
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V
VACOMED, IERMP, laboratoire de pharmacologie, Faculté de médecine de Rouen, Saint-Etienne-du-Rouvray.
Lecomte
J M
JM
Thuillez
C
C
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D004149:Dioxoles / Q000494:pharmacology*; D004285:Dogs; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects*; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D004149:Dioxoles; D004338:Drug Combinations; C068866:alatriopril; D009320:Atrial Natriuretic Factor; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin; D000409:Alanine
Effets hémodynamiques systémiques et régionaux d'un nouvel inhibiteur mixte de l'enzyme de conversion de l'angiotensine et de l'endopeptidase neutre, l'alatriopril, chez le chien.