Nitrovasodilator-induced inhibition of LTB4 release from human PMN may be mediated by cyclic GMP.
This study investigates the action of nitrovasodilators on f-metleu-phe (FMLP)-stimulated LTB4 release and intracellular cyclic nucleotide levels in human polymorphonuclear leukocytes (PMN). Sodium nitroprusside, and the molsidomine (MOL) metabolites SIN-1 and SIN-1A potently inhibited LTB4 release and increased cGMP levels. No significant effects on LTB4 release or cGMP accumulation were observed in the presence of molsidomine or glyceryl trinitrate. None of the compounds tested affected cAMP levels. It is suggested that nitrovasodilators (i) inhibit LTB4 release from human PMN via enhanced cGMP and (ii) that this inhibition requires the presence of an active metabolite, probably nitric oxide.
Ney
P
P
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Federal Republic of Germany.
Schröder
H
H
Schrör
K
K
D006152:Cyclic GMP / Q000378:metabolism*; D006801:Humans; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D009602:Nitrosamines / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D009602:Nitrosamines; D014665:Vasodilator Agents; D007975:Leukotriene B4; C006006:N-nitrosomorpholinoaminoacetonitrile; D009240:N-Formylmethionine Leucyl-Phenylalanine; C002385:linsidomine; D008981:Molsidomine; D005996:Nitroglycerin; D006152:Cyclic GMP