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Hemodynamic and cardiac effects of spiraprilat in normal and sodium depleted conscious dogs
Author(s) -
Gérard JL,
Pussard E.,
Berdeaux A.,
Giudicelli JF
Publication year - 1990
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1990.tb00039.x
Subject(s) - preload , hemodynamics , propranolol , cardiac output , heart rate , medicine , blood pressure , tachycardia , ventricular pressure , anesthesia , mean arterial pressure , cardiology , chemistry
Summary— The cardiac and hemodynamic effects of 3 doses (0.1, 0.3 and 1 mg/kg, iv) of spiraprilat, the diacid active metabolite of the new angiotensin I converting enzyme inhibitor spirapril, have been investigated and compared to those of saline in chronically implanted conscious dogs at rest. Under a normal sodium diet, spiraprilat, 1 mg/kg, induced significant (at least P <0.05) decreases in mean arterial pressure (MAP, −11%), total peripheral resistance (TPR, −21%), left ventricular end diastolic pressure (LVEDP, −15%) and increases in heart rate (HR, + 12%) and cardiac output (CO, + 16%) whereas dP/dtmax remained unchanged. Spiraprilat‐induced tachycardia was not modified by propranolol pre‐treatment but was abolished by previous administration of the propranolol‐ N ‐methylatropine combination. Spiraprilat, 0.1 mg/kg, did not affect any parameter, but spiraprilat, 0.3 mg/kg, showed intermediate effects. Finally, sodium depletion strongly potentiated spiraprilat effects on MAP, TPR, LVEDP, HR and CO. We conclude that: a), in conscious dogs under normal sodium diet, spiraprilat reduces TPR and MAP through peripheral vasodilating properties; b), spiraprilat‐induced tachycardia is mainly related to parasympathetic tone withdrawal, possibly in relation with high and low pressure baroreceptors deactivation; and c), sodium depletion considerably potentiates spiraprilat cardiac and hemodynamic effects.