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 less than 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.