TY - JOUR
T1 - Vasodilator and constrictor actions of platelet-activating factor in the isolated microperfused afferent arteriole of the rabbit kidney
T2 - Role of endothelium-derived relaxing factor/nitric oxide and cyclooxygenase products
AU - Juncos, Luis A.
AU - Ren, Yilin
AU - Arima, Shuji
AU - Ito, Sadayoshi
PY - 1993/4
Y1 - 1993/4
N2 - 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.
AB - 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.
KW - Endothelium-derived relaxing factor
KW - Microvasculature
KW - Prostaglandins
KW - Renal circulation
KW - Thromboxane
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U2 - 10.1172/JCI116339
DO - 10.1172/JCI116339
M3 - Article
C2 - 8473488
AN - SCOPUS:0027175418
VL - 91
SP - 1374
EP - 1379
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 4
ER -