Interleukin 1 and endotoxin activate soluble guanylate cyclase in vascular smooth muscle

1990 ◽  
Vol 259 (1) ◽  
pp. R38-R44 ◽  
Author(s):  
D. Beasley
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Interleukin 1 ◽  
Physiological Salt Solution ◽  
Initial Exposure ◽  
Vasodilatory Action ◽  
Ly 83583

Our recent studies indicate that interleukin 1 (IL-1) and bacterial lipopolysaccharide inhibit agonist-induced contractions in rat aortic rings by an endothelium-independent mechanism. The present study investigated the role of guanosine 3',5'-cyclic monophosphate (cGMP) in the vasodilatory action of IL-1 and endotoxin. Rat aortic rings were denuded of endothelium and incubated for 3 h in physiological salt solution containing no additions, IL-1 (20 ng/ml), or endotoxin (10 micrograms/ml). Contractions induced by phenylephrine (3 x 10(-7) M) were decreased by 40 and 85% in endotoxin- and IL-1-treated rings, respectively. IL-1 increased cGMP content 2.5-fold in the absence of and 5.5-fold in the presence of 3-isobutyl-1-methylxanthine (IBMX). Endotoxin also increased cGMP content in the absence and presence of IBMX (5.5- and 25-fold, respectively). Both IL-1- and endotoxin-induced increases in cGMP occurred 3-4 h after initial exposure. The guanylate cyclase inhibitors, LY 83583 and methylene blue, each abolished IL-1- and endotoxin-induced inhibition of contraction and IL-1-induced production of cGMP. Furthermore, hemoglobin, which binds nitric oxide, completely blocked IL-1-induced increases in cGMP. We conclude that IL-1 and endotoxin inhibit vascular contraction in vitro by increasing aortic cGMP content. Studies with inhibitors suggest IL-1 and endotoxin may induce endothelium-independent production of nitric oxide or another free radical that activates soluble guanylate cyclase.

Nitric oxide-mediated excitatory effect on neurons of dorsal motor nucleus of vagus

1994 ◽  
Vol 266 (1) ◽  
pp. G154-G160 ◽  
Author(s):  
R. A. Travagli ◽  
R. A. Gillis
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Spontaneous Discharge ◽  
Motor Nucleus ◽  
Excitatory Effect ◽  
Dorsal Motor Nucleus ◽  
Ly 83583 ◽  
Spontaneous Firing Rate

The purpose of our study was to explore whether nitric oxide was involved as an intercellular messenger in the dorsal motor nucleus of the vagus (DMV). To achieve this purpose we examined DMV motoneurons of the rat in vitro with the use of the extracellular cell-attached recording technique. The motoneurons, in general, exhibit a spontaneous discharge and when exposed to NO-producing drugs (i.e., 3-300 microM L-arginine and 10-100 microM S-nitroso-N-acetylpenicillamine) exhibit a concentration-related increase in their spontaneous firing rate. Because NO activates soluble guanylate cyclase and increases guanosine 3',5'-cyclic monophosphate (cGMP), we tested dibutyryl-cGMP (30-300 microM) and found that it also excites DMV neurons. Perfusion of the DMV neurons with N omega-nitro-L-arginine (300 microM), an inhibitor of NO synthase (NOS), and with NO scavenger, reduced hemoglobin (1 microM), counteracted the excitatory effect of L-arginine and N-methyl-D-aspartate (NMDA). Perfusion of the preparation with LY-83583 (10 microM), an inhibitor of guanylate cyclase, also counteracted the effects of L-arginine and NMDA. These data indicate that NOS is present in DMV neurons, and that the excitatory effect of NMDA on these neurons is due in part to formation of NO and the resulting accumulation of cGMP in DMV neurons.

Nitric oxide inhibits neutrophil migration by a mechanism dependent on ICAM-1: Role of soluble guanylate cyclase

Nitric Oxide ◽  
2006 ◽  
Vol 15 (1) ◽  
pp. 77-86 ◽  
Author(s):  
Daniela Dal Secco ◽  
Ana P. Moreira ◽  
Andressa Freitas ◽  
João S. Silva ◽  
Marcos A. Rossi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Neutrophil Migration

Evidence for NO ⋅ redox form of nitric oxide as nitrergic inhibitory neurotransmitter in gut

1998 ◽  
Vol 275 (5) ◽  
pp. G1185-G1192 ◽  
Author(s):  
Raj K. Goyal ◽  
Xue D. He
Keyword(s):  
Nitric Oxide ◽  
Potassium Channel ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Slow Component ◽  
Circular Muscle ◽  
Exact Nature ◽  
Channel Blockers ◽  
Inhibitory Neurotransmitter ◽  
Ly 83583

A nitric oxide (NO)-like product of thel-arginine NO synthase pathway has been shown to be a major inhibitory neurotransmitter that is involved in the slow component of the inhibitory junction potential (IJP) elicited by stimulation of nonadrenergic, noncholinergic nerves. However, the exact nature of the nitrergic transmitter, the role of cGMP, and the involvement of a potassium or a chloride conductance in the slow IJP remain unresolved. We examined the effects of soluble guanylate cyclase inhibitors LY-83583 and 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ), potassium-channel blockers and putative chloride-channel blockers diphenylamine-2-carboxylate (DPC) and niflumic acid (NFA) on the hyperpolarization elicited by an NO ⋅ donor, diethylenetriamine/NO adduct (DNO), NO in solution, and an NO+ donor, sodium nitroprusside (SNP), in the guinea pig ileal circular muscle. Effects of these blockers on purinergic (fast) and nitrergic (slow) IJP were also examined. DNO-induced hyperpolarization and nitrergic slow IJP were suppressed by LY-83583 or ODQ and DPC or NFA but not by the potassium-channel blocker apamin. In contrast, hyperpolarization caused by SNP or solubilized NO gas and purinergic fast IJP were antagonized by apamin but not by inhibitors of guanylate cyclase or chloride channels. These results demonstrate biological differences in the actions of different redox states of NO and suggest that NO ⋅ is the nitrergic inhibitory neurotransmitter.

The role of nitric oxide in the regulation of the electrical activity of the trigeminal nerve in the rat

2021 ◽  
Author(s):  
S.O. Svitko ◽  
K.S. Koroleva ◽  
G.F. Sitdikova ◽  
K.A. Petrova
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Trigeminal Nerve ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
No Synthase ◽  
The Body ◽  
No Donor ◽  
No Signaling

Nitric oxide (NO) is a gaseous signaling molecule that regulates a number of physiological functions, including its role in the formation of migraine has been established. NO is endogenously produced in the body from L-arginine by NO synthase. The NO donor, nitroglycerin, is a trigger of migraine in humans and is widely used in the modeling of this disease in animals, which suggests the involvement of components of the NO signaling cascade in the pathogenesis of migraine. Based on the results obtained, it was found that an increase in the concentration of both the substrate for the synthesis of NO, L-arginine, and the NO donor, sodium nitroprusside, has a pro-nociceptive effect in the afferents of the trigeminal nerve. In this case, the effect of sodium nitroprusside is associated with the activation of intracellular soluble guanylate cyclase. Key words: nitric oxide, migraine, trigeminal nerve, L-arginine, guanylate cyclase, sodium nitroprusside, nociception.

Involvement of nitric oxide and nitrosothiols in relaxation of pulmonary arteries to peroxynitrite

1994 ◽  
Vol 266 (5) ◽  
pp. H2108-H2113 ◽  
Author(s):  
M. Wu ◽  
K. A. Pritchard ◽  
P. M. Kaminski ◽  
R. P. Fayngersh ◽  
T. H. Hintze ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Artery ◽  
Vascular Tissue ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Arterial Tissue ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Smooth Muscle ◽  
Ly 83583

Peroxynitrite (ONOO-) is an inflammatory cell-derived oxidant, formed by the reaction of superoxide anion (O2-) with nitric oxide (NO), which was recently reported to relax vascular tissues. In the present study, the potential role of NO in the mechanism of relaxation in isolated bovine endothelium-denuded pulmonary arterial smooth muscle rings to ONOO- was evaluated. Potassium-preconstricted pulmonary arterial rings rapidly relaxed for a prolonged period of time on exposure to ONOO- (0.01-0.1 mM). The relaxation after 1 min of exposure to ONOO- (0.1 mM) was reduced 49 and 87%, respectively, by inhibitors of the stimulation of soluble guanylate cyclase, methylene blue, and LY-83583. In contrast, a scavenger of hydroxyl radicals, dimethyl sulfoxide, did not alter this response. Decomposed 0.1 mM ONOO- (which is primarily nitrite) and 0.1 mM nitrite caused a relaxation of pulmonary artery, which slowly developed over 15 min. Small quantities of NO were detected by chemiluminescence quantification methods when ONOO- was added to buffer. Exposure of pulmonary arterial tissue or buffer containing glutathione (GSH) to ONOO- caused a time-dependent increase in the observed generation of NO, whereas decomposed ONOO- produced 10% of the NO generated by ONOO- on incubation with pulmonary arterial tissue. Treatment with diethyl maleate, an agent that depletes tissue GSH, reduced both the relaxation and the formation of NO detected from pulmonary artery on exposure to ONOO-. GSH solutions treated with ONOO- appear to have generated a nitrosothiol-like vascular relaxant compound. Thus ONOO- appears to relax vascular tissue, in part, by nitrosylating tissue GSH (or other thiols), which subsequently releases NO over prolonged time periods.

Endothelin-receptor blockade does not alter closure of the ductus arteriosus

1998 ◽  
Vol 275 (5) ◽  
pp. H1620-H1626 ◽  
Author(s):  
Jeffrey R. Fineman ◽  
Yasushi Takahashi ◽  
Christine Roman ◽  
Ronald I. Clyman
Keyword(s):  
Soluble Guanylate Cyclase ◽  
Ductus Arteriosus ◽  
Late Gestation ◽  
Receptor Blockade ◽  
Active Tension ◽  
In Vitro Effects ◽  
Ly 83583

Endothelin-1 (ET-1) is synthesized within the wall of the ductus arteriosus (DA) and is a potent constrictor of the DA in vitro. However, the role of endogenous ET-1 in closure of the DA at birth remains unclear. Therefore, we studied the effects of a selective ETA-receptor antagonist (PD-156707), or its vehicle, on DA closure in 13 late-gestation fetal lambs during the first 5 h after birth. We also studied the effects of ETA-receptor blockade on DA constriction induced by oxygen, indomethacin (a cyclooxygenase inhibitor), and LY-83583 (a soluble guanylate cyclase inhibitor) in vitro ( n = 9 ductus arteriosus rings). In vehicle-treated lambs in vivo, the DA constricted during the 5-h study period after birth: DA resistance increased (from 0.007 ± 0.01 to 3.406 ± 4.15 mmHg ⋅ ml−1 ⋅ min ⋅ kg−1; P < 0.05); the pressure gradient across the DA increased (from 1.4 ± 2.1 to 25.2 ± 9.4 mmHg; P < 0.05); and DA blood flow decreased (from 193.5 ± 48.0 to 19.3 ± 14.3 ml ⋅ kg−1 ⋅ min−1; P < 0.05). In vitro, the DA was constricted by exposure to 30% oxygen (23 ± 14% net active tension; P < 0.05), indomethacin (5 × 10−6 M, 22 ± 5% net active tension; P < 0.05), LY-83583 (10−5 M, 24 ± 10% net active tension; P < 0.05), and ET-1 (10−7 M, 19 ± 4% net active tension; P < 0.05). Although PD-156707 blocked both the in vivo and in vitro effects of exogenous ET-1, it had no effect on postnatal ductus constriction nor on in vitro ductus contractile responses to oxygen, indomethacin, or LY-83583. This study suggests that endogenous ET-1 does not play an important role in closure of the DA at birth.

scholarly journals Vasorelaxant and antiplatelet activity of 4,7-dimethyl-1,2,5-oxadiazolo[3,4-d ]pyridazine 1,5,6-trioxide: role of soluble guanylate cyclase, nitric oxide and thiols

2000 ◽  
Vol 129 (6) ◽  
pp. 1163-1177 ◽  
Author(s):  
Alexander Ya Kots ◽  
Mikhail A Grafov ◽  
Yuri V Khropov ◽  
Vasily L Betin ◽  
Natalya N Belushkina ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Antiplatelet Activity

Role of nitric oxide in adenosine receptor-mediated relaxation of porcine coronary artery

1995 ◽  
Vol 269 (5) ◽  
pp. H1672-H1678 ◽  
Author(s):  
W. Abebe ◽  
T. Hussain ◽  
H. Olanrewaju ◽  
S. J. Mustafa
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Porcine Coronary Artery ◽  
Cyclic Monophosphate ◽  
Enhanced Production ◽  
Cgs 21680 ◽  
Synthase Inhibitor ◽  
Ly 83583

In the present study, using porcine coronary artery rings in vitro, we examined the role of the nitric oxide (NO) pathway in endothelium-dependent vasorelaxant effects of the 5'-uronamide adenosine agonists, 5'-(N-ethylcarboxamido)adenosine (NECA) and 2-[p-(2-carboxyethyl)]phenylethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS-21680) as opposed to the endothelium-independent actions of the C2- and N6-substituted analogues, 2-chloroadenosine (CAD) and N6-cyclopentyladenosine (CPA). The NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 30 microM), and the NO-destroying agent, 6-anilino-5,8-quinolinedione (LY-83583, 10 microM), attenuated the relaxations of endothelium-intact but not -denuded rings to NECA and CGS-21680. The effect of L-NMMA on NECA-induced relaxation was reversed by L-arginine (100 microM), a substrate for NO synthesis. In the endothelium-intact tissues, both NECA and CGS-21680 elicited enhanced production of nitrite, a stable metabolite of NO. This was also attenuated by L-NMMA or endothelium removal. Furthermore, NECA (10 microM) induced augmentation of guanosine 3',5'-cyclic monophosphate (cGMP) production in the intact arteries, which was also inhibited by L-NMMA, LY-83583, or endothelium removal. In contrast, vasorelaxant responses generated by CAD and CPA were not altered by either L-NMMA or LY-83583. Both agents (10 microM) were also unable to alter nitrite and/or guanosine 3',5'-cyclic monophosphate (cGMP) levels of the coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Interleukin 1 activates soluble guanylate cyclase in human vascular smooth muscle cells through a novel nitric oxide-independent pathway.

1994 ◽  
Vol 179 (1) ◽  
pp. 71-80 ◽  
Author(s):  
D Beasley ◽  
M McGuiggin
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Interleukin 1 ◽  
No Synthase ◽  
Guanylate Cyclase Activation

Recent demonstration of cytokine-inducible production of nitric oxide (NO) in vascular smooth muscle cells (VSMC) from rat aorta has implicated VSMC-derived NO as a key mediator of hypotension in septic shock. Our studies to determine whether an inducible NO pathway exists in human VSMC have revealed a novel cytokine-inducible, NO-independent pathway of guanylate cyclase activation in VSMC from human saphenous vein (HSVSMC). Interleukin 1 (IL-1), tumor necrosis factor (TNF), interferon gamma (IFN-gamma) and Escherichia coli lipopolysaccharide (LPS) increased cGMP at 24 h, whereas IL-2 and IL-6 were ineffective. The effect of IL-1 on cyclic guanosine 3',5'-monophosphate (cGMP) was delayed, occurring after 6 h of exposure, and was maximal after 10 h. Methylene blue and LY83583 reversed the IL-1-induced increase in cGMP, suggesting that it was mediated by activation of soluble guanylate cyclase. However, IL-1-induced cGMP in HSVSMC was not inhibited by extracellular hemoglobin. Also, the effect of IL-1 on cGMP was not reversed by nitro- or methyl-substituted L-arginine analogs, aminoguanidine, or diphenyleneiodonium, all of which inhibit IL-1-induced NO synthase in rat aortic VSMC (RAVSMC). IL-1-induced cGMP in HSVSMC was also independent of tetrahydrobiopterin and extracellular L-arginine, as it was not affected by 2,4-diamino-6-hydroxyprytimidine, an inhibitor of tetrahydrobiopterin biosynthesis, and was similar in L-arginine-free and L-arginine-containing media. Analysis of NO synthase mRNA with the use of polymerase chain reaction indicates that levels of mRNA for inducible NO synthase are several orders of magnitude lower in IL-1-treated human HSVSMC than in IL-1-treated RAVSMC. IL-1-induced cGMP was also NO independent in human umbilical artery VSMC, and NO dependent in rat vena cava VSMC. Together these results indicate that IL-1 activates a novel NO-independent pathway of soluble guanylate cyclase activation in human VSMC.

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