Arginine is a physiological precursor of endothelium-derived nitric oxide

120

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evidence for nitric oxide as mediator of non‐adrenergic, non‐cholinergic relaxations induced by ATP and GABA in the canine gut

Boeckxstaens

Pelckmans

Bult

et al. 1991

120

“…We have also provided evidence against NO as a cotransmitter of sympathetic nerves. NO is synthesized from the semi-essential amino acid Larginine (Palmer et al, 1988a,b;Schmidt et al, 1988;Moncada et al, 1991) by NO synthase. L-NMMA and L-NAME are specific inhibitors of NO synthesis (Palmer et al, 1988b;Johns et al, 1990;Moore et al, 1990;Moncada et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Role of nitric oxide and guanosine 3′,5′‐cyclic monophosphate in mediating nonadrenergic, noncholinergic relaxation in guinea‐pig pulmonary arteries

Liu

Crawley

Rohde

et al. 1992

1 Nonadrenergic, noncholinergic (NANC) nerves mediate vasodilatation in guinea-pig pulmonary artery (PA) by both endothelium-dependent and endothelium-independent mechanisms. The transmitter(s) involved in the endothelium-independent pathway have not yet been identified. We have therefore investigated the possibility that nitric oxide (NO) and guanosine 3',5'-cyclic monophosphate (cyclic GMP) may mediate this neural vasodilator response in guinea-pig branch PA rings denuded of endothelium. 2 Electric field stimulation (EFS, 50 V, 0.2 ms) induced a frequency-dependent (1-24 Hz), tetrodotoxin-sensitive relaxation of the U44069-precontracted PA rings in the presence of adrenergic and cholinergic blockade. 3 The NO synthase inhibitors NG-monomethyl L-arginine (L-NMMA, 100 pM) and NG-nitro L-arginine methyl ester (L-NAME, 30 pM), and the guanylyl cyclase inhibitor methylene blue (5 pM) inhibited the EFS (16 Hz)-induced relaxation by 53 ± 5, 74 + 9 and 82 ± 9% respectively (n = 5-7, P<0.01, compared with control rings).4 Excess concentrations of L-, but not D-arginine (300 gM) completely reversed the inhibitory effect of L-NMMA. 5 The EFS-elicited relaxation (4 Hz) was potentiated by 1 gM zaprinast, a type V phosphodiesterase inhibitor which inhibits guanosine 3':5'-cyclic monophosphate (cyclic GMP) degradation, but was unaffected by 0.1 gM zardaverine, a type III/IV phosphodiesterase inhibitor which inhibits cyclic AMP degradation. 6 EFS (50 V, 0.2 ms, 16 Hz) induced a 3 fold increase in tissue cyclic GMP content, an action which was inhibited by L-NMMA (100;LM).7 Pyrogallol (100IM), a superoxide anion generator, also inhibited the EFS-induced relaxation by 53 ± 9%, and this effect was prevented by superoxide dismutase. 8 Chemical sympathetic denervation with 6-hydroxydopamine had no effect on the relaxant response to EFS in the endothelium-denuded PA rings.9 In endothelium-denuded branch PA rings at resting tone, L-NMMA (100 JM) significantly augmented the adrenergic contractile response, an effect which was completely reversed by L-arginine, but not by D-arginine. In the same groups of vessel rings, L-NMMA had no significant effect on the matched contractile response to exogenous noradrenaline. 10 These results suggest that NO may be released from intramural nerve endings other than adrenergic nerves (probably NANC nerves), and this leads to vasodilatation via activation of guanylyl cyclase.

“…PG12 is a metabolite derived from the 20 carbon fatty acid, arachidonic acid (AA; Moncada et al, 1976) whereas EDRF is NO or a related molecule (Palmer et al, 1987;Myers et al, 1990) formed from L-arginine (Palmer et al, 1988;Schmidt et al, 1988). The biosynthetic pathways of EDRF and PG12 also differ with regard to substrate availability.…”

Section: Introductionmentioning

confidence: 99%

Different patterns of release of endothelium‐derived relaxing factor and prostacyclin

Mitchell¹,

Nucci²,

Warner³

et al. 1992

1 Release of endothelium derived relaxing factor (EDRF) and prostacyclin (PGO2) from endothelial cells (EC) cultured from bovine aortae was measured by bioassay and radioimmunoassay, respectively, during infusions (10min) of bradykinin (BK), adenosine diphosphate (ADP), arachidonic acid (AA), alkaline buffers and the free-bases (FB) of L-arginine or D-arginine. Release of EDRF from the luminally perfused rabbit aorta was also measured during infusions (10 min) of acetylcholine (ACh), substance P and ADP. 2 Bradykinin (10 or 30 nM) infused through the column of EC induced release of both EDRF and PGO2, neither of which was maintained for the duration of the infusion. 3 ADP (1.6 or 4pM) infused through the column of EC induced release of a EDRF which was maintained for the duration of the infusion and a release of PGO2 which lasted for a much shorter period. 4 Arachdonic acid (30 or 90 pM) infused through the column of EC caused a sustained release of EDRF and PGI2, both of which outlasted the infusion of AA.