Platelet activating factor vasoconstriction of dog kidney. Inhibition by alprazolam.
Systemic administration of platelet activating factor (PAF; acetyl glyceryl ether phosphorylcholine) reduces renal blood flow, but the mechanism responsible for that effect has not been defined. To address that problem, we determined the effects on renal blood flow of PAF administered directly into the renal artery in pentobarbital (30 mg/kg)-anesthetized dogs. Bolus injections of PAF (0.2-0.8 microgram) caused transient renal vasoconstriction, reducing renal blood flow by 20 to 60% without altering systemic blood pressure; lyso-PAF (1 microgram) had no effect. The effects of PAF on renal blood flow were not altered by alpha-adrenergic blockade (phentolamine, 3 mg/kg) or by angiotensin II receptor blockade ([Sar1,Ala8]angiotensin II, 6 micrograms/kg/min), but they were increased in magnitude and duration by meclofenamate (5 mg/kg), a cyclooxygenase inhibitor. Methysergide (3 mg/kg), a serotonin antagonist, slightly reduced PAF effects, but a specific blocker of vascular serotonin receptors did not. Renal venous plasma platelet density was not altered by infusion of PAF into the renal artery at a dose (1-2 micrograms/min) that caused a sustained 20% renal blood flow decrease. Alprazolam, a benzodiazepine that competitively inhibited PAF-induced aggregation in canine platelet-rich plasma, also inhibited the renal vasoconstrictor action of PAF (0.8 mg/min, into the renal artery) but did not alter renal vasoconstrictor effects of norepinephrine or angiotensin II.
D000525:Alprazolam / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D004873:Ergolines; D010972:Platelet Activating Factor; D008469:Meclofenamic Acid; D012504:Saralasin; C032663:LY 53857; D008784:Methysergide; D000525:Alprazolam