ciprokiren and Cardiac-Output--Low

To determine the role of the renin-angiotensin system and the bradykinin pathway in the mechanism of action of angiotensin-converting enzyme inhibitors in heart failure, the acute effects of enalaprilat (1 mg/kg) were compared with those of a renin inhibitor (ciprokiren, 1 mg/kg i.v.) in 10 chronically instrumented conscious dogs with heart failure induced by right ventricular pacing (3 wk, 240 beats/min). The effects of enalaprilat and ciprokiren on bradykinin infusion (3, 10, and 30 micrograms/min) and the effects of enalaprilat in the presence of the bradykinin B2 receptor antagonist Hoe-140 (10 micrograms/kg i.v.) were also examined. Both inhibitors significantly decreased mean aortic pressure and increased cardiac output. However, enalaprilat induced significantly greater hemodynamic effects than ciprokiren (mean aortic pressure, -13 +/- 3 vs. -6 +/- 1 mmHg; cardiac output, 0.4 +/- 0.1 vs. 0.15 +/- 0.1 l/min). Bradykinin infusion led to dose-dependent decreases in mean aortic pressure and increases in cardiac output that were not modified by pretreatment with ciprokiren but were potentiated 10-fold by enalaprilat. Hoe-140 significantly reduced the hemodynamic effects of enalaprilat. Thus endogenous bradykinin is involved in the acute hemodynamic effects of enalaprilat in experimental heart failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Bradykinin Receptor Antagonists; Cardiac Output, Low; Dogs; Enalaprilat; Female; Hemodynamics; Hormones; Imidazoles; Male; Renin; Time Factors

To determine the role of the renin-angiotensin system in a model of acute heart failure.. Placebo or drugs (Ro 44-9375, a renin inhibitor; captopril, an angiotensin-converting enzyme [ACE] inhibitor; or DuP 532, an angiotensin II receptor [AT1] antagonist) were given to anesthetized splenectomized dogs (n = 12 for each group) for 50 mins after a volume load (dextran 70, 25 mL/kg over 10 mins) during rapid right ventricular pacing at 250 beats/min. Total vascular compliance and capacitance were determined from mean circulatory filling pressure-blood volume curves during transient circulatory arrests induced by acetylcholine. Cardiac index was measured by thermal dilution.. Compared with the untreated group, all three drugs significantly reduced systemic pressure and total peripheral resistance while increasing arterial compliance. Captopril alone increased cardiac index (25 +/- 11 versus -23 +/- 13 mL/kg/min) and reduced pulmonary capillary wedge pressure (16.6 +/- 0.7 versus 21.9 +/- 1.0 mmHg). None of the drugs altered the mean circulatory filling pressure, total vascular compliance or capacitance, stressed or unstressed blood volumes, or central blood volume.. The renin-angiotensin system is not strongly implicated in the hemodynamic manifestations of this model of acute heart failure. These drugs had effects on the arterial but not the venous side of the circulation. Captopril alone reduced pulmonary capillary wedge pressure, perhaps by nonangiotensin effects.

Topics: Acute Disease; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Blood Volume; Captopril; Cardiac Output, Low; Cardiac Pacing, Artificial; Dogs; Dose-Response Relationship, Drug; Female; Imidazoles; Male; Renin-Angiotensin System; Stroke Volume; Tetrazoles; Vascular Resistance; Ventricular Function, Left