Comparison of responses to histamine by constant-flow and constant-pressure perfusion methods in the rabbit isolated kidney preparation.

ABSTRACT

1. Reproducibility and sensitivity of responses of isolated perfused rabbit renal vascular bed to bolus administration of histamine was compared for the conditions of constant-flow and constant-pressure perfusion by Krebs-Henseleit solution. Two other vasoactive agents (noradrenaline and angiotensin II) were also tested in the same preparation for comparison 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 and were evaluated as changes of perfusion pressure or flow, to correspond to drug activities at the resistance vessels and, also, change of organ weight, as effects on exchange and capacitance functions of the circulation. Both parameters were also recorded on a Grass polygraph. 4. Reproducibility and sensitivity of responses to vasoactive agents (histamine, noradrenaline, angiotensin II) were significantly low in the constant-flow conditions, compared to constant-pressure mode. 5. Responsivity also deviated for different perfusion pressures of constant-pressure mode and 80-100 mm H2O pressure was found to be the most convenient value. 6. It is concluded that constant-flow and constant-pressure conditions provide different hydrodynamic conditions. In constant-flow methodology, when the predetermined perfusion rate is not tolerated by the vascular bed, excessive flow in the circulation would lead to depression of vasoactivity, failing pharmacodynamic equilibria and loss of responsivity. Structural deviation of the vascular bed would also be expected due to differences of organ specimen and, probably, result in the variation of responsivity of constant-flow perfusion procedure.