Vasodilator and constrictor actions of platelet-activating factor in the isolated microperfused afferent arteriole of the rabbit kidney: Role of endothelium-derived relaxing factor/nitric oxide and cyclooxygenase products

Luis A. Juncos, Yilin Ren, Shuji Arima, Sadayoshi Ito

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

It has been suggested that platelet-activating factor (PAF) plays a prominent role in the control of glomerular hemodynamics in various physiological and pathological conditions. We examined the direct effect of PAF on rabbit glomerular afferent arterioles (Af-Arts) microperfused in vitro and tested whether endothelium-derived relaxing factor/nitric oxide (EDNO) and cyclooxygenase products are involved in its actions. In nanomolar concentrations PAF caused dose-dependent constriction of Af-Arts, with the maximum constriction being 34±10% at 4 × 10-8 M (n = 9, P < 0.001 ). The constriction was blunted by cyclooxygenase inhibition (11±6%, n = 7, P < 0.05) but augmented by EDNO inhibition (76±14%, n = 8, P < 0.005). To study a possible vasodilator effect of PAF, Af-Arts were preconstricted with norepinephrine and increasing concentrations of PAF added to the lumen. At picomolar concentrations (lower than those that caused constriction), PAF produced dose-dependent vasodilation that was unaffected by cyclooxygenase inhibition but was abolished by EDNO synthesis inhibition. Both PAF-induced constriction and dilation of Af-Arts were blocked by a PAF receptor antagonist. This study demonstrates that PAF has a receptor-mediated biphasic effect on rabbit Af-Arts, dilating them at low concentrations while constricting them at higher concentrations. Our results suggest that PAF's vasodilator action may be due to production of EDNO, while its constrictor action is mediated at least in part through cyclooxygenase products.

Original languageEnglish
Pages (from-to)1374-1379
Number of pages6
JournalJournal of Clinical Investigation
Volume91
Issue number4
DOIs
Publication statusPublished - 1993 Apr

Keywords

  • Endothelium-derived relaxing factor
  • Microvasculature
  • Prostaglandins
  • Renal circulation
  • Thromboxane

ASJC Scopus subject areas

  • Medicine(all)

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