Acute hemodynamic effects of drugs acting on the renin-angiotensin system in acute heart failure.
OBJECTIVE
To determine the role of the renin-angiotensin system in a model of acute heart failure.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Clinical Pharmacology Service, Toronto Hospital, Ontario.
A A
AA
Nekooeian
R I
RI
Ogilvie
D
D
Zborowska-Sluis
D000208:Acute Disease; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001810:Blood Volume / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D002303:Cardiac Output, Low / Q000503:physiopathology / Q000628:therapy*; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D005466:Fluorocarbons
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D007093:Imidazoles; D013777:Tetrazoles; C069045:DuP 532; D005466:Fluorocarbons; C085570:ciprokiren