Effect of PD 123319, an AT-2 antagonist, on renal function of the anesthetized dog: comparison with EXP 3174, an AT-1 blocker

Kidney & Blood Pressure Research
J Heller, V Horácek

Abstract

In anaesthetized dogs fed a diet delivering 3.5 mmol NaCl/kg/day, PD 123319 - an angiotensin (AT) II (Ang II) antagonist preferentially bound to AT-2 receptors - was infused into the renal artery for 20 min at 10 microg/kg/min, the lowest effective dose (group 1 dogs). In group 2 dogs, EXP 3174 (30 microg/kg/min) - an AT-1 blocker - was coinfused while, in group 3, EXP 3174 was infused alone. In all groups, during and immediately after infusion, increased sodium, water, and urea excretions from the infused but not from the contralateral kidney were seen. This increase was the same in all groups throughout the infusion; however, in groups infused with EXP 3174, it persisted even after the infusion had been discontinued. Thus, the total amounts of sodium and water excreted during the whole experiment were higher when EXP 3174 was present in the infusion solution than after PD 123319 alone. Moreover, an increase in glomerular filtration rate (creatinine clearance) and renal blood flow (electromagnetic flowmeter) was seen during the infusion period in groups receiving EXP 3174, but not PD 123319. Although it is possible to assume that blockade of AT-1 receptors only is responsible for the changes in excretion rates as PD 123319 is ...Continue Reading

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