5-HT-induced colonic contractions: enteric locus of action and receptor subtypes

1997 ◽  
Vol 273 (1) ◽  
pp. G68-G74 ◽  
Author(s):  
S. Graf ◽  
S. K. Sarna
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Contractile Response ◽  
No Synthase ◽  
Enteric Neurons ◽  
Receptor Subtypes ◽  
Arterial Infusion ◽  
Stimulation Of

The role of 5-hydroxytryptamine (5-HT), its enteric locus of action, and the receptor subtypes involved in the stimulation of in vivo phasic contractions in the colon were investigated by close intra-arterial infusions in conscious dogs. The contractile response to 5-HT was blocked completely by prior close intra-arterial infusion of atropine and reduced significantly by prior close intra-arterial infusions of tetrodotoxin and hexamethonium. The contractile response was, however, enhanced by the inhibition of nitric oxide (NO) synthase by a prior close intra-arterial infusion of N omega-nitro-L-arginine methyl ester. Prior close intra-arterial infusions of 5-HT1A/5-HT1B, 5-HT2A, 5-HT2C, and 5-HT4 receptor antagonists had no significant effect on the contractile response to 5-HT. By contrast, 5-HT3 receptor antagonist significantly and dose dependently inhibited the contractile response to 5-HT. We conclude that the in vivo phasic contractile response to 5-HT in the colon is mediated mainly by 5-HT3 receptors located on pre- and postsynaptic cholinergic enteric neurons. 5-HT receptors may also be localized on nonadrenergic, noncholinergic inhibitory motoneurons that use NO as a neurotransmitter.

Selective autonomic stimulation of canine trachealis with dimethylphenylpiperazinium

1981 ◽  
Vol 51 (2) ◽  
pp. 428-437 ◽  
Author(s):  
A. R. Leff ◽  
N. M. Munoz
Keyword(s):  
Adrenal Gland ◽  
Contractile Response ◽  
Sympathetic Innervation ◽  
Adrenergic Stimulation ◽  
Parasympathetic Ganglia ◽  
Regional Administration ◽  
Adrenal Secretion ◽  
Stimulation Of

The response of canine tracheal muscle to autonomic stimulation with 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) was studied isometrically in 39 dogs in vivo. Intra-arterial (ia) DMPP (2.5 X 10(-4) to 2.5 X 10(-2) mg/kg) caused selective dose related contraction [maximum 30.1 +/- 6.5 gram-force (gf)/cm] due to regional stimulation of parasympathetic ganglia. This contraction was blocked by regional administration of atropine 10(-3) mg/kg ia and hexamethonium 5 X 10(-2) mg/kg ia. Nonselective intravenous (iv) administration of DMPP 2.5 X 10(-2) mg/kg caused parasympathetic tracheal contraction [+13.4 +/- 1.64 gf/cm] followed by later sympathetic relaxation [-11.8 +/- 2.3 gf/cm]; 0.5 mg/kg iv atropine abolished contraction but did not affect relaxation. The role of the adrenal gland vs. direct sympathetic innervation in producing tracheal relaxation after sympathetic stimulation was also studied. Tracheal relaxation to 2.5 X 10(-2) mg/kg iv DMPP was -18.2 +/- 4.0 gf/cm before adrenalectomy (ADX) and -4.3 +/- 0.9 gf/cm afterward (P less than 0.001). In contrast, tracheal contraction resulting from alpha-adrenergic stimulation after 2.5 X 10(-2) mg/kg iv DMPP in beta-blocked (BB) dogs was not significantly altered by ADX. At 2.5 X 10(-1) mg/kg iv DMPP, the alpha-adrenergic contractile response was still 70% of the response prior to ADX. We conclude that sympathetic tracheal relaxation in dogs is predominantly mediated by circulating catecholamine from the adrenal gland, but that alpha-adrenergic contraction after BB results predominantly from direct sympathetic innervation and is not greatly augmented by adrenal secretion. We also report a new method for selective stimulation of airway cholinergic nerves in vivo without systemic effects.

Compensatory role of NO in cerebral circulation of piglets chronically treated with indomethacin

2002 ◽  
Vol 282 (2) ◽  
pp. R400-R410 ◽  
Author(s):  
Yifan Zhang ◽  
C. W. Leffler
Keyword(s):  
Nitric Oxide ◽  
Cerebrospinal Fluid ◽  
Methyl Ester ◽  
Cerebral Circulation ◽  
No Synthase ◽  
Inhibitory Effects ◽  
Circulatory Control ◽  
Pial Arterioles ◽  
Indomethacin Treatment

We hypothesize that inhibitory effects exist between prostanoids and nitric oxide (NO) in their contributions to cerebral circulation. Piglets (1–4 days old) were divided into three chronically treated (6–8 days) groups: control piglets, piglets treated with indomethacin (75 mg/day), and piglets treated with N ω-nitro-l-arginine methyl ester (l-NAME, 100 mg · kg−1 · day−1). Pial arterioles dilated in response to hypercapnia similarly among the three groups (41 ± 4, 40 ± 6, and 45 ± 11%). Cerebrospinal fluid cAMP increased in control piglets, while cGMP increased in indomethacin-treated piglets. l-NAME, but not 7-nitroindazole, inhibited the response to hypercapnia only in indomethacin-treated piglets (40 ± 6 vs. 17 ± 5%). Topical sodium nitroprusside or iloprost restored dilation in response to hypercapnia. Similar results were obtained when the dilator was bradykinin. Pial arterioles of control and l-NAME-treated piglets constricted in response to ACh (−24 ± 3%). However, those of indomethacin-treated piglets dilated in response to ACh (15 ± 2%). This dilation was inhibited by l-NAME. NO synthase activity, but not endothelial NO synthase expression, increased after chronic indomethacin treatment. These data suggest that chronic inhibition of cyclooxygenase can increase the contribution of NO to cerebrovascular circulatory control in piglets.

Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium

1996 ◽  
Vol 270 (1) ◽  
pp. H411-H415 ◽  
Author(s):  
L. Morbidelli ◽  
C. H. Chang ◽  
J. G. Douglas ◽  
H. J. Granger ◽  
F. Ledda ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Growth Factor ◽  
No Synthase ◽  
Mitogenic Effect ◽  
Microvascular Endothelium ◽  
Proliferative Effect

Vascular endothelial growth factor (VEGF) is a secreted protein that is a specific growth factor for endothelial cells. We have recently demonstrated that nitric oxide (NO) donors and vasoactive peptides promoting NO-mediated vasorelaxation induce angiogenesis in vivo as well as endothelial cell growth and motility in vitro; in contrast, inhibitors of NO synthase suppress angiogenesis. In this study we investigated the role of NO in mediating the mitogenic effect of VEGF on cultured microvascular endothelium isolated from coronary postcapillary venules. VEGF induced a dose-dependent increase in cell proliferation and DNA synthesis. The role of NO was determined by monitoring proliferation or guanosine 3',5'-cyclic monophosphate (cGMP) levels in the presence and absence of NO synthase blockers. The proliferative effect evoked by VEGF was reduced by pretreatment of the cells with NO synthase inhibitors. Exposure of the cells to VEGF induced a significant increment in cGMP levels. This effect was potentiated by superoxide dismutase addition and was abolished by NO synthase inhibitors. VEGF stimulates proliferation of postcapillary endothelial cells through the production of NO and cGMP accumulation.

scholarly journals The role of the endothelium in the hyperemic response to passive leg movement: looking beyond nitric oxide

2020 ◽  
Author(s):  
Joel D. Trinity ◽  
Oh Sung Kwon ◽  
Ryan M. Broxterman ◽  
Jayson R. Gifford ◽  
Andrew C. Kithas ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Vascular Function ◽  
No Synthase ◽  
Ketorolac Tromethamine ◽  
Arterial Infusion ◽  
Healthy Men ◽  
Leg Movement ◽  
Hyperemic Response

Passive leg movement (PLM) evokes a robust and predominantly nitric oxide (NO)-mediated increase in blood flow that declines with age and disease. Consequently, PLM is becoming increasingly accepted as a sensitive assessment of endothelium-mediated vascular function. However, a substantial PLM-induced hyperemic response is still evoked despite NO synthase (NOS) inhibition. Therefore, in 9 young healthy men (25±4 yrs), this investigation aimed to determine if the combination of two potent endothelium-dependent vasodilators, specifically prostaglandin (PG) and endothelium-derived hyperpolarizing factor (EDHF), account for the remaining hyperemic response to the two variants of PLM, PLM (60 movements) and single PLM (sPLM, 1 movement) when NOS is inhibited. The leg blood flow (LBF, Doppler ultrasound) response to PLM and sPLM following the intra-arterial infusion of NG-monomethyl L-arginine (L-NMMA), to inhibit NOS, was compared to the combined inhibition of NOS, cyclooxygenase (COX), and cytochrome P450 (CYP450) by L-NMMA, ketorolac tromethamine (KET), and fluconazole (FLUC), respectively. NOS inhibition attenuated the overall LBF (LBFAUC) response to both PLM (control: 456±194, L-NMMA: 168±127 ml, p<0.01) and sPLM (control: 185±171, L-NMMA: 62±31 ml, p=0.03). The combined inhibition of NOS, COX, and CYP450 (i.e. L-NMMA+KET+FLUC) did not further attenuate the hyperemic responses to PLM (LBFAUC: 271±97 ml, p>0.05) or sPLM (LBFAUC: 72±45 ml, p>0.05). Therefore, PG and EDHF do not collectively contribute to the non-NOS-derived NO-mediated, endothelium-dependent, hyperemic response to either PLM or sPLM in healthy young men. These findings add to the mounting evidence and understanding of the vasodilatory pathways assessed by the PLM and sPLM vascular function tests.

In vivo treatment with endotoxin induces nitric oxide synthase in rat main pulmonary artery

1995 ◽  
Vol 268 (3) ◽  
pp. L509-L518 ◽  
Author(s):  
M. J. Griffiths ◽  
S. Liu ◽  
N. P. Curzen ◽  
M. Messent ◽  
T. W. Evans
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Contractile Response ◽  
Main Pulmonary Artery ◽  
Pulmonary Arteries ◽  
No Synthase ◽  
Oxide Synthase ◽  
Lps Treatment

Our aim was to demonstrate increased NO activity from inducible NO synthase (iNOS) in pulmonary arteries (PA) from rats treated with endotoxin [lipopolysaccharide (LPS), 20 mg/kg ip]. LPS treatment diminished the contractile response of PA to potassium chloride (KCl) and phenylephrine (PE) and increased levels of guanosine 3',5'-cyclic monophosphate (cGMP) in endothelium-denuded vessels. Both the NO synthase (NOS) antagonists NG-monomethyl-L-arginine (L-NMMA; nonselective) and aminoguanidine (selective for iNOS) enhanced PE-induced contraction in endothelium-denuded vessels from LPS-treated rats. Furthermore, L-NMMA-induced contraction of endothelium-denuded vessels from LPS-treated rats was stereospecifically antagonized by L-arginine and associated with decreased cGMP levels. These data suggest that NO is produced in increased amounts from PA smooth muscle after LPS treatment. LPS treatment caused increased expression of mRNA for iNOS in PA. This effect of LPS was attenuated by pretreatment with dexamethasone, suggesting that induction of NOS in PA smooth muscle underlies the increased NO activity associated with LPS administration.

Role of G proteins in the vasodilator response to endothelin isopeptides in vivo

1995 ◽  
Vol 78 (6) ◽  
pp. 2062-2069
Author(s):  
H. L. Lippton ◽  
Q. Hao ◽  
O. Erdemli ◽  
A. Hyman
Keyword(s):  
Katp Channels ◽  
Receptor Subtypes ◽  
Vasomotor Tone ◽  
Arterial Infusion ◽  
Vasodilator Response ◽  
Vascular Bed ◽  
Pulmonary Vasodilator ◽  
Transduction Mechanisms

The purpose of the present study was to determine the influence of pertussis toxin (PTX) on the pulmonary and systemic vasodilator responses to endothelin (ET) isopeptides in the intact cat under conditions of constant pulmonary blood flow and left atrial pressure. When pulmonary vasomotor tone was actively increased by an intralobar arterial infusion of U-46619, intralobar arterial bolus injections of ET-1, ET-2, and ET-3 decreased lobar arterial pressure and systemic vascular resistance in a dose-related manner. The vasodilator responses to ET-1 and ET-2 in the cat lung were abolished by PTX pretreatment, whereas PTX pretreatment did not alter the pulmonary vasodilator response to ET-3 and cromakalim, a specific ATP-sensitive potassium (KATP) channel activator, and the systemic vasodilator responses to all ET isopeptides studied. Glipizide, an inhibitor of KATP channels, inhibited the pulmonary vasodilator responses to ET-1, ET-2, and ET-3, whereas the systemic vasodilator responses to these isopeptides were not changed. The present data are the first to provide a functional correlate in vivo suggesting the existence of different signal transduction mechanisms for two pulmonary vascular ET receptor subtypes, ETA-like that is PTX sensitive and has greater sensitivity to ET-1 and ET-2 (than to ET-3) and ETc-like that is PTX insensitive and has sensitivity to ET-3 (than to ET-1 and ET-2). However, both ET-receptor subtypes promote vasodilation in the adult pulmonary vascular bed by activating KATP channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of nitric oxide in hypoxia-induced colonic dysfunction in the neonatal rat

1997 ◽  
Vol 272 (4) ◽  
pp. G760-G769 ◽  
Author(s):  
J. F. Brown ◽  
B. L. Tepperman
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Protein Content ◽  
No Synthase ◽  
Neonatal Rat ◽  
Myeloperoxidase Activity ◽  
Neonatal Rats ◽  
Colonic Tissue ◽  
Colonic Injury

In addition to being an important mediator in the regulation of intestinal integrity, nitric oxide (NO), when produced in large quantities by the inducible isoform of NO synthase, can also be cytotoxic. The aim of this study was to examine the role of NO in hypoxia-induced colonic injury in neonatal rats. Rats (10-12 days old) were exposed to a hypoxic environment of 14% O2-86% N2 for 30 min. NO synthase activity in colonic tissue was measured via the conversion of L-[14C]arginine to L-[14C]citrulline. Epithelial permeability was assessed by measuring the plasma-to-lumen flux of [3H]mannitol or the luminal protein content of colonic lavage. The role of neutrophils was assessed by pretreatment with antineutrophil serum (200 microl/kg ip) and measurement of tissue myeloperoxidase activity. Hypoxia resulted in an elevation in the activity of the inducible Ca2+-independent isoform of NO synthase in colonic tissue, which was maximal between 4 and 6 h posthypoxia and was associated with an increase in myeloperoxidase activity, [3H]mannitol flux, luminal protein content, and histological damage. These effects were attenuated by pretreatment with dexamethasone or the NO synthase inhibitors aminoguanidine and N(G)-nitro-L-arginine methyl ester, whereas the inactive stereoisomer N(G)-nitro-D-arginine methyl ester was without effect. Pretreatment with antineutrophil serum significantly reduced circulating neutrophils, myeloperoxidase activity, and Ca2+-independent NO synthase activity. These findings demonstrate that hypoxia-induced colonic injury in neonatal rats is associated with elevated NO synthase activity, which is related to an increase in neutrophil infiltration.

Nitric oxide mediates human chorionic gonadotrophin-induced prostaglandin E generation in rat oocyte - cumulus complexes

1997 ◽  
Vol 9 (4) ◽  
pp. 391 ◽  
Author(s):  
Alicia Jawerbaum ◽  
Elida T. Gonzalez ◽  
Alicia Faletti ◽  
Virginia Novaro ◽  
Martha A. F. Gimeno
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
No Synthase ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Prostaglandin E ◽  
No Donors ◽  
Nos Inhibitors ◽  
Preovulatory Follicles

To determine whether nitric oxide (NO) generation mediates human chorionic gonadotrophin (hCG)-induced prostaglandin E (PGE) secretion by oocyte–cumulus complexes (OCC), the secretion of PGE by cultured rat OCC in the presence of NO donors and NO synthase (NOS) inhibitors was characterized. NO donors (sodium nitroprusside and 3-morpholino-sydnonimine- hydrochloride) increased PGE accumulation in OCC to values similar to those obtained in the presence of hCG. The three NOS inhibitors tested (N G -nitro-L-arginine methyl ester, NG -monomethyl-L-arginine and aminoguanidine) prevented the hCG-induced PGE accumulation in cultured OCC. This effect appears to be specific since D-enantiomers NG -nitro-D-arginine methyl ester and NG -monomethyl-D-arginine had no effect. The present results suggest that NO mediates the hCG-induced accumulation of PGE in rat OCC, a process which may occur in vivo in preovulatory follicles prior to ovulation.

Endogenous vasodilators modulate pulmonary vascular anaphylaxis

1994 ◽  
Vol 76 (2) ◽  
pp. 916-922 ◽  
Author(s):  
L. J. Kelly ◽  
B. J. Undem ◽  
G. K. Adams
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Methyl Ester ◽  
Guinea Pig ◽  
Initial Phase ◽  
Contractile Response ◽  
Pulmonary Arteries ◽  
Relaxing Factor ◽  
Anaphylactic Contraction

We examined the role of endothelium-derived nitric oxide during antigen-induced contraction in pulmonary arteries isolated from actively sensitized guinea pigs. Ovalbumin (10(-2) mg/ml)-induced contraction was not sustained, and tension returned to baseline within 15 min. Pretreatment with methylene blue (10(-5) M) increased both the amplitude and the duration of the contractile response in these tissues. At 15 min, tension remained elevated and was > 70% of the peak amplitude. Removal of the endothelium with saponin (200 micrograms/ml) increased the magnitude of the contraction by > 125%; however, the duration of the response was unaffected. After pretreatment with saponin, methylene blue no longer increased the amplitude of antigen-induced contraction but its effect on the duration was unchanged. Pretreatment with nitro-L-arginine methyl ester significantly increased the magnitude of the contraction in each of the tissues. These results suggest that the response of guinea pig pulmonary arteries to antigen is modulated by two types of endogenous vasodilators, endothelium-derived nitric oxide that inhibits the initial phase of the response and an endothelium-independent relaxing factor that is guanosine 3′,5′-cyclic monophosphate dependent and attenuates the duration of anaphylactic contraction.

scholarly journals Role of Nitric Oxide in Regulating Cerebrocortical Oxygen Consumption and Blood Flow during Hypercapnia

1994 ◽  
Vol 14 (3) ◽  
pp. 503-509 ◽  
Author(s):  
Ildiko Horvath ◽  
Norbert T. Sandor ◽  
Zoltan Ruttner ◽  
Alan C. McLaughlin
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Methyl Ester ◽  
Superior Sagittal Sinus ◽  
No Synthase ◽  
Sagittal Sinus ◽  
No Synthase Inhibitor ◽  
Synthase Inhibitor

The effect of the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) on the response of cerebrocortical oxygen consumption (CMRO2) and blood flow (CBF) to two levels of hypercapnia (Paco2 ∼ 60 mm Hg and Paco2 ∼ 90 mm Hg) was investigated in ketamine-anesthetized rats. CBF was calculated using the Kety–Schmidt approach and CMRO2 was calculated from the product of CBF and the arteriovenous (superior sagittal sinus) difference for oxygen. l-NAME treatment did not have a significant effect on either CMRO2 or CBE under normocapnic conditions but inhibited the hypercapnic increase of CMRO2 and the hypercapnic increase in CBF. These results suggest that NO plays a role in the response of CMRO2 and CBF during hypercapnia and are consistent with the suggestion that at least part of the increase in CBF observed during hypercapnia is coupled to an increase in CMRO2.

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