COMPARISON OF RESPONSES TO HISTAMINE BY CONSTANT-FLOW AND CONSTANT-PRESSURE PERFUSION METHODS IN THE RABBIT ISOLATED KIDNEY PREPARATION

1. Reproducibility and sensitivity of responses of isolated perfused r abbit renal vascular bed to bolus administration of histamine was comp ared for the conditions of constant-flow and constant-pressure perfusi on by Krebs-Henseleit solution. Two other vasoactive agent (noradrenal ine and angiotensin II) were also tested in the same preparation for c omparison with the effect of histamine. 2. In constant-pressure mode, different hydrostatic pressures were also employed for the analysis of time-effect phenomena. 3. Drug responses were recorded by computer an d were evaluated as changes of perfusion pressure or flow, to correspo nd to drug activities at the resistance vessels and, also, change of o rgan weight, as effects on exchange and capacitance functions of the c irculation. Both parameters were also recorded on a Grass polygraph. 4 . Reproducibility and sensitivity of responses to vasoactive agents (h istamine, noradrenaline, angiotensin II) were significantly low in the constant-flow conditions, compared to constant-pressure mode. 5. Resp onsivity also deviated for different perfusion pressures of constant-p ressure mode and 80-100 mm H2O pressure was found to be the most conve nient value. 6. It is concluded that constant-flow and constant-pressu re conditions provide different hydrodynamic conditions. In constant-f low methodology, when the predetermined perfusion rate is not tolerate d by the vascular bed, excessive flow in the circulation would lead to depression of vasoactivity, failing pharmacodynamic equilibria and lo ss of responsivity. Structural deviation of the vascular bed would als o be expected due to differences of organ specimen and, probably, resu lt in the variation of responsivity of constant-flow perfusion procedu re.