title: Platelet-activating factor and solute transport processes in the kidney.
abstract: We examined the hemodynamic and tubular transport mechanisms by which platelet-activating factor (PAF) regulates salt and water excretion. In anesthetized, renally denervated male Wistar rats, with raised systemic blood pressure and renal arterial blood pressure maintained at normal levels, intrarenal PAF infusion at 2.5 ng. min(-1) x kg(-1) resulted in a small fall in systemic blood pressure (no change in renal arterial blood pressure) and an increase in renal blood flow and urinary water, sodium, and potassium excretion rates. The PAF-induced changes in cardiovascular and renal hemodynamic function were abolished and renal excretory function greatly attenuated by treating rats with a nitric oxide synthase inhibitor. To determine whether a tubular site of action was involved in the natriuretic effect of PAF, cortical proximal tubules were enzymatically dissociated from male Wistar rat kidneys, and oxygen consumption rates (Qo(2)) were used as an integrated index of transcellular sodium transport. PAF at 1 nM maximally inhibited Qo(2) in both untreated and nystatin-stimulated (sodium entry into renal cell is not rate limiting) proximal tubules by approximately 20%. Blockade of PAF receptors or Na(+)-K(+)-ATPase pump activity with BN-52021 or ouabain, respectively, abolished the effect of PAF on nystatin-stimulated proximal tubule Qo(2). Inhibition of nitric oxide synthase or guanylate cyclase systems did not alter PAF-mediated inhibition of nystatin-stimulated proximal tubule Qo(2), whereas phospholipase A(2) or cytochrome-P-450 monooxygenase inhibition resulted in a 40-60% reduction. These findings suggest that stimulation of PAF receptors on the proximal tubule decreases transcellular sodium transport by activating phospholipase A(2) and the cytochrome-P-450 monooxygenase pathways that lead to the inhibition of an ouabain-sensitive component of the basolateral Na(+)-K(+)-ATPase pump. Thus PAF can activate both an arachidonate pathway-mediated suppression of proximal tubule sodium transport and a nitric oxide pathway-mediated dilatory action on renal hemodynamics that likely contributes to the natriuresis and diuresis observed in vivo.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. rajash_handa@hotmail.com
authors.forename: Rajash K
authors.initials: RK
authors.lastname: Handa
authors.forename: Jack W
authors.initials: JW
authors.lastname: Strandhoy
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Giammattei
authors.forename: Shelly E
authors.initials: SE
authors.lastname: Handa
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004573:Electrolytes / Q000652:urine; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D012076:Renal Agents / Q000494:pharmacology; D012077:Renal Artery / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D004573:Electrolytes; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012076:Renal Agents; D014475:Uncoupling Agents; C039351:platelet activating factor receptor; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000254:Sodium-Potassium-Exchanging ATPase