Key result
Leukotriene D4 suppresses ANF-induced glomerular cGMP production by ~53% at peak concentration.
Why the study?
The effects of leukotriene D4 on atrial natriuretic factor-dependent cGMP production in the glomerulus were not well understood.
Absolute Event Rate: 1.43% vs 3.06%
p-value: p=<0.05
LTD4 inhibits ANF-induced cGMP production in rat glomeruli by selectively inhibiting the particulate guanylate cyclase system.
LTD4 may blunt ANF glomerular signaling; leaves open its role in renal sodium handling or disease models.
The effects of leukotriene D4 (LTD4) on guanosine 3',5'-cyclic monophosphate (cGMP) production induced by atrial natriuretic factor (ANF) or sodium nitroprusside (SNP) were investigated in isolated rat glomeruli. First, the isolated glomeruli were preincubated in Krebs-Ringer buffer containing 3-isobutyl-1-methylxanthine for 10 min, then incubated with varying concentrations of ANF, SNP, and LTD4 for 3 min. cGMP content was determined by radioimmunoassay. cGMP production (fmol.glomerulus-1.3 min-1) was not increased by LTD4. cGMP accumulation was increased by ANF (1 microM) and SNP (100 microM) remarkably from 0.19 +/- 0.09 to 3.24 +/- 0.21 (n = 7, mean +/- SE), and from 0.19 +/- 0.09 to 3.67 +/- 0.47 (n = 4), respectively. The increase in cGMP production by ANF was significantly and dose-dependently inhibited by LTD4 (P less than 0.05). Maximum suppression was observed at the concentration of 100 nM (from 3.06 +/- 0.33 to 1.43 +/- 0.09; P less than 0.05). However, LTD4 caused no significant change in the level of cGMP production induced by SNP. Second, particulate or soluble guanylate cyclase from glomeruli were similarly investigated. ANF selectively activated particulate guanylate cyclase and the response was selectively inhibited by LTD4 from 9.07 +/- 1.79 fmol.micrograms-1.3 min-1 (n = 6) to 4.70 +/- 0.70 (n = 6, P less than 0.05). These results suggest the site where LTD4 has effect on cGMP production induced by ANF was the particulate guanylate cyclase system, but not the soluble guanylate cyclase system.
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Terada et al. (1989) studied this question. Leukotriene D4 (LTD4) vs. Atrial natriuretic factor (ANF) alone was evaluated on cGMP production induced by ANF (fmol.glomerulus-1.3 min-1) (p=<0.05). Leukotriene D4 significantly and dose-dependently inhibited atrial natriuretic factor-induced cGMP production in isolated rat glomeruli, with maximum suppression at 100 nM (P<0.05).
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