Renovascular and tubular effects of neuropeptide Y are discriminated by PP56 (D-myo-inositol 1,2,6-triphosphate) in anaesthetized rats.
Systemic infusion of neuropeptide Y (NPY; 1 microg kg-1 min-1) for 120 min rapidly reduced renal blood flow and increased mean arterial pressure and renovascular resistance and, at later time points (> 30 min), enhanced diuresis, natriuresis and calciuresis in anaesthetized rats. Infusion of the reported NPY antagonist PP56 (D-myo-inositol 1,2,6-triphosphate, 333 mg kg-1 min-1) slightly but significantly enhanced renal blood flow and reduced renovascular resistance over the course of the infusion period. Infusion of PP56 together with NPY (starting 30 min prior to the NPY infusion) significantly inhibited NPY-induced alterations of mean arterial pressure, renal blood flow and renovascular resistance. Coinfusion of PP56 also attenuated the renovascular effects of bolus injections of NPY (0.1-10 microg/kg) but at the highest NPY dose the antagonistic effect of PP56 could partially be overcome. In contrast to the antagonism of the vascular NPY effects, infusion of PP56 did not significantly affect NPY-induced enhancements of diuresis, natriuresis and calciuresis. Thus, PP56 is a surmountable antagonist of vascular but not tubular NPY effects. We conclude that tubular NPY effects occur largely independently of alterations of renal haemodynamics.
Bischoff
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A
Nephrol. Lab. IG 1, Klinikum, Hufelandstrasse 55, D-45122 Essen, Germany.
Stickan-Verfürth
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M
Michel
M C
MC
D000758:Anesthesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000494:pharmacology*; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects*
D007295:Inositol Phosphates; D009478:Neuropeptide Y; D010975:Platelet Aggregation Inhibitors; C059368:atrinositol