scholarly journals The nitric oxide/cGMP pathway couples muscarinic receptors to the activation of Ca2+ influx

1996 ◽  
Vol 16 (5) ◽  
pp. 1702-1709 ◽  
Author(s):  
C Mathes ◽  
SH Thompson
Keyword(s):  
Nitric Oxide ◽  
Muscarinic Receptors ◽  
Cgmp Pathway

Insulin sensitivity is mediated by the activation of the ACh/NO/cGMP pathway in rat liver

2004 ◽  
Vol 287 (3) ◽  
pp. G527-G532 ◽  
Author(s):  
Maria P. Guarino ◽  
Nina C. Correia ◽  
W. Wayne Lautt ◽  
M. Paula Macedo
Keyword(s):  
Nitric Oxide ◽  
Insulin Sensitivity ◽  
Muscarinic Receptors ◽  
Wistar Rats ◽  
No Donor ◽  
Parasympathetic Nerves ◽  
Cgmp Pathway ◽  
Male Wistar Rats ◽  
Oxide Synthase

The hepatic parasympathetic nerves and hepatic nitric oxide synthase (NOS) are involved in the secretion of a hepatic insulin sensitizing substance (HISS), which mediates peripheral insulin sensitivity. We tested whether binding of ACh to hepatic muscarinic receptors is an upstream event to the synthesis of nitric oxide (NO), which, along with the activation of hepatic guanylate cyclase (GC), permits HISS release. Male Wistar rats (8–9 wk) were anesthetized with pentobarbital sodium (65 mg/kg). Insulin sensitivity was assessed using a euglycemic clamp [the rapid insulin sensitivity test (RIST)]. HISS inhibition was induced by antagonism of muscarinic receptors (atropine, 3 mg/kg iv) or by blockade of NOS [ NG-nitro-l-arginine methyl ester (l-NAME), 1 mg/kg intraportally (ipv)]. After the blockade, HISS action was tentatively restored using a NO donor [3-morpholynosydnonimine (SIN-1), 5–10 mg/kg ipv] or ACh (2.5–5 μg·kg−1·min−1 ipv). SIN-1 (10 mg/kg) reversed the inhibition caused by atropine (RIST postatropine 137.7 ± 8.3 mg glucose/kg; reversed to 288.3 ± 15.5 mg glucose/kg, n = 6) and by l-NAME (RIST post-l-NAME 152.2 ± 21.3 mg glucose/kg; reversed to 321.7 ± 44.7 mg glucose/kg, n = 5). ACh did not reverse HISS inhibition induced by l-NAME. The role of GC in HISS release was assessed using 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 nmol/kg ipv), a GC inhibitor that decreased HISS action (control RIST 237.6 ± 18.6 mg glucose/kg; RIST post-ODQ 111.7 ± 6.2 mg glucose/kg, n = 5). We propose that hepatic parasympathetic nerves release ACh, leading to hepatic NO synthesis, which activates GC, triggering HISS action.

Polychlorinated Biphenyls PCB 153 and PCB 126 Impair the Glutamate–Nitric Oxide–cGMP Pathway in Cerebellar Neurons in Culture by Different Mechanisms

2009 ◽  
Vol 16 (2) ◽  
pp. 97-105 ◽  
Author(s):  
Marta Llansola ◽  
Blanca Piedrafita ◽  
Regina Rodrigo ◽  
Carmina Montoliu ◽  
Vicente Felipo
Keyword(s):  
Nitric Oxide ◽  
Polychlorinated Biphenyls ◽  
Cerebellar Neurons ◽  
Pcb 126 ◽  
Cgmp Pathway

Nitric oxide modulates cardiac performance in the heart of Anguilla anguilla

2001 ◽  
Vol 204 (10) ◽  
pp. 1719-1727 ◽  
Author(s):  
S. Imbrogno ◽  
L. De Iuri ◽  
R. Mazza ◽  
B. Tota
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Cardiac Output ◽  
Anguilla Anguilla ◽  
Cardiac Performance ◽  
Stroke Work ◽  
Nos Inhibitors ◽  
Cgmp Pathway ◽  
Triton X ◽  
Endocardial Endothelium

Nothing is known about the effects of nitric oxide (NO) on cardiac performance in fish. Using an in vitro working heart preparation that generates physiological values of output pressure, cardiac output and ventricular work and power, we assessed the effects of NO on the cardiac performance of the eel Anguilla anguilla. We examined basal cardiac performance (at constant preload, afterload and heart rate), the effects of cholinergic stimulation and the Frank-Starling response (preload-induced increases in cardiac output at constant afterload and heart rate). The NO synthase (NOS) inhibitors N(G)-monomethyl-l-arginine (l-NMMA) and l-N(5)(1-iminoethyl)ornithine (l-NIO), the guanylate cyclase inhibitor 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ) and Triton X-100, a detergent that damages the endocardial endothelium, all increased stroke volume (V(S)) and stroke work (W(S)). In contrast, the endogenous NOS substrate l-arginine, tested before and after treatment with haemoglobin, the NO donor 3-morpholinosydnonimine, tested with and without the superoxide scavenger superoxide dismutase, and the stable cGMP analogue 8-bromoguanosine 3′,5′-cyclic monophosphate (8-Br-cGMP) decreased V(S) and W(S). Acetylcholine chloride produced a biphasic effect. At nanomolar concentrations, in 34 % of the preparations, it induced a NO-cGMP-dependent positive inotropism that required the integrity of the endocardial endothelium. Pretreatment with Triton X-100 or with NO-cGMP pathway inhibitors (l-NMMA, l-NIO, N(G)-nitro-l-arginine methyl ester, Methylene Blue and ODQ) abolished the positive effect of acetylcholine. In contrast, at micromolar concentrations, acetylcholine produced a negative effect that involved neither the endocardial endothelium nor the NO-cGMP pathway. Pre-treatment with l-arginine (10(−)(6)mol l(−)(1)) was without effect, whereas l-NIO (10(−)(5)mol l(−)(1)) significantly reduced the Frank-Starling response. Taken together, these three experimental approaches provide evidence that NO modulates cardiac performance in the eel heart.

Inhibition of vascular nitric oxide-cGMP pathway by plasma from ischemic hindlimb of rats

1995 ◽  
Vol 269 (1) ◽  
pp. H254-H261 ◽  
Author(s):  
J. S. Jin ◽  
R. C. Webb ◽  
L. G. D'Alecy
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Superoxide Dismutase ◽  
Contractile Activity ◽  
Femoral Vein ◽  
Guanylate Cyclase Activity ◽  
Cgmp Pathway ◽  
Induced Hypertension ◽  
Control Plasma

The hypothesis was tested that plasma from ischemic hindlimbs facilitates hypertension. Ischemia-induced hypertension was generated in rats by infrarenal aortic cross clamping for 5 h after which plasma was obtained from femoral vein blood. In vitro contractile activity of naive aortic rings incubated for 2 h in plasma collected from ischemic rats demonstrated reduced relaxation to acetylcholine and nitroglycerin. Methylene blue (10(-5) M) induced greater contraction in rings incubated in control vs. ischemic plasma, suggesting that endogenous guanylate cyclase activity is decreased by ischemic plasma. However, 8-bromo-guanosine 3',5'-cyclic monophosphate (cGMP) relaxed equally strips incubated in ischemic or control plasma. Acetylcholine-induced nitrite release was significantly lower in ischemic vs. control plasma-incubated strips (8.6 +/- 2.7 vs. 28.2 +/- 2.3 ng/10 mg tissue wt, respectively). The impaired relaxation to acetylcholine in ischemic plasma-incubated rings was significantly increased by L-arginine but not by prior treatment of ischemic plasma with heating or superoxide dismutase and catalase. These findings suggest the impaired relaxation is mediated through inhibition of the nitric oxide-cGMP pathway. Prolonged blunting of vasodilation by ischemic plasma may therefore contribute to maintenance of a sustained vasoconstriction and ischemic hypertension.

Vasomodulatory effect of novel peroxovanadate compounds on rat aorta: Role of rho kinase and nitric oxide/cGMP pathway

2011 ◽  
Vol 64 (3) ◽  
pp. 274-282 ◽  
Author(s):  
Vivek Khanna ◽  
Manish Jain ◽  
Manoj Kumar Barthwal ◽  
Diganta Kalita ◽  
Jeena Jyoti Boruah ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Rho Kinase ◽  
Rat Aorta ◽  
Cgmp Pathway

scholarly journals Enteric descending and afferent neural signaling stimulated by giant migrating contractions: essential contributing factors to visceral pain

2007 ◽  
Vol 292 (2) ◽  
pp. G572-G581 ◽  
Author(s):  
Sushil K. Sarna
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Nitric Oxide Synthase ◽  
Muscarinic Receptors ◽  
Visceral Pain ◽  
Intestinal Segment ◽  
Descending Inhibition ◽  
Oxide Synthase ◽  
Stimulation Of ◽  
Giant Migrating Contractions

We investigated whether strong compression of an intestinal segment by giant migrating contractions (GMCs) initiates pseudoaffective signals from the gut, similar to those initiated by its distension with a balloon. The experiments were performed on conscious dogs by using close intra-arterial infusions of test substances that affect the receptors only in the infused segment. The stimulation of GMCs by close intra-arterial infusion of CGRP or distension of an intestinal segment by balloon increased the heart rate; the increase in heart rate was greater when the balloon distension and GMCs occurred concurrently in separate intestinal segments. The suppression of contractility in the distended segment blocked the increase in heart rate. By contrast, the stimulation of rhythmic phasic contractions (RPCs) or their spontaneous occurrence did not increase the heart rate. The occurrence of GMCs as well as intestinal distension also produced descending inhibition. The descending inhibition was blocked by the inhibition of nitric oxide synthase, but it was unaffected by the inhibition of adenylyl cyclase, purinergic receptors P2X and P2Y, and muscarinic receptors M1 and M2. The synaptic transmission for descending inhibition was mediated primarily by nicotinic receptors and activation of nitric oxide synthase. It was unaffected by the inhibition of tachykinin receptors NK1, NK2, and NK3; serotonin receptors 5-HT1A, 5-HT2/5-HT1C, 5-HT3, and 5-HT4; and muscarinic receptors. Our findings show that GMCs, but not RPCs, initiate pseudoaffective signals from the gut. In the presence of visceral hypersensitivity or impaired descending inhibition, the GMCs may become a noxious stimulus.

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