Nitric Oxide Is Essential for Generating the Minute Rhythm Contraction Pattern in the Small Intestine, Likely via ICC-DMP

Nitrergic nerves have been proposed to play a critical role in the orchestration of peristaltic activities throughout the gastrointestinal tract. In the present study, we investigated the role of nitric oxide, using spatiotemporal mapping, in peristaltic activity of the whole ex vivo mouse intestine. We identified a propulsive motor pattern in the form of propagating myogenic contractions, that are clustered by the enteric nervous system into a minute rhythm that is dependent on nitric oxide. The cluster formation was abolished by TTX, lidocaine and nitric oxide synthesis inhibition, whereas the myogenic contractions, occurring at the ICC-MP initiated slow wave frequency, remained undisturbed. Cluster formation, inhibited by block of nitric oxide synthesis, was fully restored in a highly regular rhythmic fashion by a constant level of nitric oxide generated by sodium nitroprusside; but the action of sodium nitroprusside was inhibited by lidocaine indicating that it was relying on neural activity, but not rhythmic nitrergic nerve activity. Hence, distention-induced activity of cholinergic nerves and/or a co-factor within nitrergic nerves such as ATP is also a requirement for the minute rhythm. Cluster formation was dependent on distention but was not evoked by a distention reflex. Block of gap junction conductance by carbenoxolone, dose dependently inhibited, and eventually abolished clusters and contraction waves, likely associated, not with inhibition of nitrergic innervation, but by abolishing ICC network synchronization. An intriguing feature of the clusters was the presence of bands of rhythmic inhibitions at 4–8 cycles/min; these inhibitory patches occurred in the presence of tetrodotoxin or lidocaine and hence were not dependent on nitrergic nerves. We propose that the minute rhythm is generated by nitric oxide-induced rhythmic depolarization of the musculature via ICC-DMP.

Download Full-text

Inhibition of Endogenous Nitric Oxide Synthesis Potentiates the Effects of Sodium Nitroprusside but Not of Adenosine in Experimental Pulmonary Hypertension

Pharmacology ◽

10.1159/000028266 ◽

1999 ◽

Vol 58 (1) ◽

pp. 34-43 ◽

Cited By ~ 4

Author(s):

Michael H. Wall ◽

Kenneth W. Patterson ◽

Brian P. Kavanagh ◽

RonaldG. Pearl

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Sodium Nitroprusside ◽

Nitric Oxide Synthesis ◽

Endogenous Nitric Oxide

Download Full-text

Effect of inhibition of nitric oxide synthesis on the diaphragmatic microvascular response to hypoxia

Journal of Applied Physiology ◽

10.1152/jappl.1996.81.4.1633 ◽

1996 ◽

Vol 81 (4) ◽

pp. 1633-1641 ◽

Cited By ~ 6

Author(s):

Michael E. Ward

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Ex Vivo ◽

Severe Hypoxia ◽

Nitric Oxide Synthesis ◽

Moderate Hypoxia ◽

Vessel Size ◽

Microvascular Response ◽

No Release ◽

Before And After

Ward, Michael E. Effect of inhibition of nitric oxide synthesis on the diaphragmatic microvascular response to hypoxia. J. Appl. Physiol. 81(4): 1633–1641, 1996.—The purpose of this study was to determine the effect of inhibition of nitric oxide (NO) release on the diaphragmatic microvascular responses to hypoxia. In α-chloralose-anesthetized mongrel dogs, the microcirculation of the vascularly isolated ex vivo left hemidiaphragm was studied by intravital microscopy. The diaphragm was pump perfused with blood diverted from the femoral artery through a series of membrane oxygenators. The responses to supramaximal concentrations of sodium nitroprusside, moderate hypoxia (phrenic venous [Formula: see text] 27 Torr), and severe hypoxia (phrenic venous [Formula: see text] 15 Torr) were recorded before and after an infusion of N G-nitro-l-arginine (l-NNA; 6 × 10−4 M) into the phrenic circulation for 20 min. Under control conditions, diaphragmatic blood flow was 12.4 ± 1.1 ml ⋅ min−1 ⋅ 100 g−1. Diaphragmatic blood flows recorded during moderate and severe hypoxia were 15.6 ± 1.2 and 24.3 ± 1.5 ml ⋅ min−1 ⋅ 100 g−1, respectively ( P < 0.05 for both compared with control values). Treatment withl-NNA reduced diaphragmatic blood flow to 9.6 ± 0.8 ml ⋅ min−1 ⋅ 100 g−1 under control conditions ( P < 0.05) and caused arteriolar vasoconstriction to a degree that was dependent on vessel size (i.e., larger vessels constricted more than smaller vessels).l-NNA eliminated the increase in blood flow during moderate hypoxia and inhibited arteriolar dilation by an amount that was related to vessel size (i.e., dilation of larger vessels was inhibited more than that of smaller vessels). Inhibition of NO synthesis had no effect on the increase in diaphragmatic blood flow (23.6 ± 1.9 ml ⋅ min−1 ⋅ 100 g−1; P > 0.05 compared with that during severe hypoxia before treatment withl-NNA) or arteriolar diameters during severe hypoxia. NO release plays a role in the diaphragmatic vascular response to hypoxia, but this role is limited to dilation of larger arterioles during hypoxia of moderate severity.

Download Full-text

Arbuscular mycorrhizal symbiosis modifies the effects of a nitric oxide donor (sodium nitroprusside;SNP) and a nitric oxide synthesis inhibitor (Nω-nitro-L-arginine methyl ester;L-NAME) on lettuce plants under well watered and drought conditions

Symbiosis ◽

10.1007/s13199-017-0486-3 ◽

2017 ◽

Vol 74 (1) ◽

pp. 11-20 ◽

Cited By ~ 6

Author(s):

Beatriz Sánchez-Romera ◽

Rosa Porcel ◽

Juan Manuel Ruiz-Lozano ◽

Ricardo Aroca

Keyword(s):

Nitric Oxide ◽

Methyl Ester ◽

Sodium Nitroprusside ◽

Arbuscular Mycorrhizal ◽

Arbuscular Mycorrhizal Symbiosis ◽

Nitric Oxide Donor ◽

Mycorrhizal Symbiosis ◽

Nitric Oxide Synthesis ◽

Synthesis Inhibitor ◽

Drought Conditions

Download Full-text

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

Clinical Science ◽

10.1042/cs20190999 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2283-2299

Author(s):

Apabrita Ayan Das ◽

Devasmita Chakravarty ◽

Debmalya Bhunia ◽

Surajit Ghosh ◽

Prakash C. Mandal ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Chronic Inflammation ◽

Ex Vivo ◽

Human Subjects ◽

Critical Role ◽

Atherosclerotic Cardiovascular Disease ◽

Tnf Α ◽

Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

Download Full-text