Selective inhibition of vasoconstrictor responses by platelet-activating factor in rat kidney.
We examined the effect of platelet-activating factor (PAF) on renal vascular reactivity in the pentobarbital sodium-anesthetized male Wistar rat. Intrarenal infusion of C16-PAF at hypotensive (2.5 ng.min-1.kg-1) or nonhypotensive (0.5 ng.min-1.kg-1) doses caused renal vasodilation and dose dependently antagonized the renal vasoconstrictor responses of intrarenal boluses of angiotensin II (ANG II) greater than norepinephrine (NE) greater than vasopressin (AVP). PAF infusion at the high dose did not alter non-receptor-mediated renal vasoconstriction induced by intrarenal KCl injection. The inhibitory effect of PAF on agonist-induced renal vasoconstriction was accentuated by eicosanoid synthesis inhibition (indomethacin or dexamethasone), unaffected by dopamine-receptor blockade (haloperidol) but was totally abolished by PAF receptor antagonism (L-659,989). In contrast, intrarenal infusion of a calcium channel antagonist (nimodipine) or an intracellular calcium channel antagonist (TMB-8) equally inhibited the renal vasoconstrictor responses of ANG II, NE, and AVP. Thus PAF can cause renal vasodilation in the rat kidney and dose-dependently antagonizes the renal vasoconstrictor responses of ANG II greater than NE greater than AVP. The inhibitory effect of PAF on renal vasoconstrictor responses is mediated by PAF receptors and does not appear to be due to a nonspecific membrane effect, reduction in calcium mobilization, or the release of vasodilatory eicosanoids or dopamine.
Handa
R K
RK
Department of Medicine/Nephrology and Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157.
Strandhoy
J W
JW
Buckalew
V M
VM
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006400:Hematocrit; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D018492:Dopamine Antagonists; D005663:Furans; D010972:Platelet Activating Factor; C054893:L 659989; D016718:Arachidonic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D009553:Nimodipine; D005707:Gallic Acid; D011189:Potassium Chloride; D006220:Haloperidol