Ca2+-independent PLA2 controls endothelial store-operated Ca2+ entry and vascular tone in intact aorta

2008 ◽  
Vol 295 (6) ◽  
pp. H2466-H2474 ◽  
Author(s):  
François-Xavier Boittin ◽  
Françoise Gribi ◽  
Karima Serir ◽  
Jean-Louis Bény
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Physiological Mechanism ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Arterial Tone ◽  
Endothelium Dependent Relaxation ◽  
Stimulation Of

During an agonist stimulation of endothelial cells, the sustained Ca2+ entry occurring through store-operated channels has been shown to significantly contribute to smooth muscle relaxation through the release of relaxing factors such as nitric oxide (NO). However, the mechanisms linking Ca2+ stores depletion to the opening of such channels are still elusive. We have used Ca2+ and tension measurements in intact aortic strips to investigate the role of the Ca2+-independent isoform of phospholipase A2 (iPLA2) in endothelial store-operated Ca2+ entry and endothelium-dependent relaxation of smooth muscle. We provide evidence that iPLA2 is involved in the activation of endothelial store-operated Ca2+ entry when Ca2+ stores are artificially depleted. We also show that the sustained store-operated Ca2+ entry occurring during physiological stimulation of endothelial cells with the circulating hormone ATP is due to iPLA2 activation and significantly contributes to the amplitude and duration of ATP-induced endothelium-dependent relaxation. Consistently, both iPLA2 metabolites arachidonic acid and lysophosphatidylcholine were found to stimulate Ca2+ entry in native endothelial cells. However, only the latter triggered endothelium-dependent relaxation through NO release, suggesting that lysophosphatidylcholine produced by iPLA2 upon Ca2+ stores depletion may act as an intracellular messenger that stimulates store-operated Ca2+ entry and subsequent NO production in endothelial cells. Finally, we found that ACh-induced endothelium relaxation also depends on iPLA2 activation, suggesting that the iPLA2-dependent control of endothelial store-operated Ca2+ entry is a key physiological mechanism regulating arterial tone.

scholarly journals A theoretical model of nitric oxide transport in arterioles: frequency- vs. amplitude-dependent control of cGMP formation

2004 ◽  
Vol 286 (3) ◽  
pp. H1043-H1056 ◽  
Author(s):  
Nikolaos M. Tsoukias ◽  
Mahendra Kavdia ◽  
Aleksander S. Popel
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Soluble Guanylate Cyclase ◽  
Muscle Tone ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Cgmp Formation

Nitric oxide (NO) plays many important physiological roles, including the regulation of vascular smooth muscle tone. In response to hemodynamic or agonist stimuli, endothelial cells produce NO, which can diffuse to smooth muscle where it activates soluble guanylate cyclase (sGC), leading to cGMP formation and smooth muscle relaxation. The close proximity of red blood cells suggests, however, that a significant amount of NO released will be scavenged by blood, and thus the issue of bioavailability of endothelium-derived NO to smooth muscle has been investigated experimentally and theoretically. We formulated a mathematical model for NO transport in an arteriole to test the hypothesis that transient, burst-like NO production can facilitate efficient NO delivery to smooth muscle and reduce NO scavenging by blood. The model simulations predict that 1) the endothelium can maintain a physiologically significant amount of NO in smooth muscle despite the presence of NO scavengers such as hemoglobin and myoglobin; 2) under certain conditions, transient NO release presents a more efficient way for activating sGC and it can increase cGMP formation severalfold; and 3) frequency-rather than amplitude-dependent control of cGMP formation is possible. This suggests that it is the frequency of NO bursts and perhaps the frequency of Ca2+ oscillations in endothelial cells that may limit cGMP formation and regulate vascular tone. The proposed hypothesis suggests a new functional role for Ca2+ oscillations in endothelial cells. Further experimentation is needed to test whether and under what conditions in silico predictions occur in vivo.

Interactions between nitroglycerin and endothelium in vascular smooth muscle relaxation

1991 ◽  
Vol 260 (3) ◽  
pp. H698-H701 ◽  
Author(s):  
J. L. Dinerman ◽  
D. L. Lawson ◽  
J. L. Mehta
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Cyclic Monophosphate ◽  
The Mean ◽  
Smooth Muscle Relaxant ◽  
Vascular Smooth Muscle Relaxation

To evaluate the role of endothelium in nitroglycerin (NTG)-mediated vascular relaxation, epinephrine-contracted rat thoracic aortic segments with and without intact endothelium were exposed to NTG (10(-10) to 10(-5) M). Aortic segments with intact (endo+, n = 15) and denuded endothelium (endo-, n = 9) exhibited typical NTG-induced relaxation. However, the mean effective concentration of NTG was lower for endo- than for endo+ segments (P less than 0.001). To determine if this phenomenon related to nitric oxide (NO) generation by endothelium, six endo+ segments were treated with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO production. These endo+ segments exhibited greater (P less than 0.001) relaxation in response to NTG than the untreated endo+ segments. Oxyhemoglobin, an inhibitor of guanylate cyclase activation, greatly diminished NTG-mediated relaxation of all aortic segments. To determine if the enhanced NTG-mediated relaxation of endo- segments was unique to the guanosine 3',5'-cyclic monophosphate-dependent vasodilator NTG, other endo+ and endo- segments were exposed to adenosine 3',5'-cyclic monophosphate-dependent vasodilator papaverine (10(-8) to 10(-4) M), and no difference in EC50 was noted between endo+ and endo- segments. Thus endothelium attenuates NTG-mediated vasorelaxation, and this attenuation is abolished by inhibition of endothelial NO production with L-NMMA. These observations indicate that endothelium is a dynamic modulator of vascular smooth muscle relaxant effects of NTG. This modulation appears to result from a competitive interaction between endothelial NO and NTG.

scholarly journals Nitric Oxide: From Gastric Motility to Gastric Dysmotility

2021 ◽  
Vol 22 (18) ◽  
pp. 9990
Author(s):  
Eglantina Idrizaj ◽  
Chiara Traini ◽  
Maria Giuliana Vannucchi ◽  
Maria Caterina Baccari
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Gastric Motility ◽  
Muscle Relaxation ◽  
Physiological Role ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Main Role ◽  
Motor Responses

It is known that nitric oxide (NO) plays a key physiological role in the control of gastrointestinal (GI) motor phenomena. In this respect, NO is considered as the main non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmitter responsible for smooth muscle relaxation. Moreover, many substances (including hormones) have been reported to modulate NO production leading to changes in motor responses, further underlying the importance of this molecule in the control of GI motility. An impaired NO production/release has indeed been reported to be implicated in some GI dysmotility. In this article we wanted to focus on the influence of NO on gastric motility by summarizing knowledge regarding its role in both physiological and pathological conditions. The main role of NO on regulating gastric smooth muscle motor responses, with particular reference to NO synthases expression and signaling pathways, is discussed. A deeper knowledge of nitrergic mechanisms is important for a better understanding of their involvement in gastric pathophysiological conditions of hypo- or hyper-motility states and for future therapeutic approaches. A possible role of substances which, by interfering with NO production, could prove useful in managing such motor disorders has been advanced.

Role of cGMP in relaxation of vascular and other smooth muscle

1989 ◽  
Vol 67 (4) ◽  
pp. 251-262 ◽  
Author(s):  
Kanji Nakatsu ◽  
Jack Diamond
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscles ◽  
Phosphodiesterase Inhibitors ◽  
Current Evidence ◽  
Smooth Muscle Relaxation ◽  
Drug Induced ◽  
Intracellular Cgmp ◽  
Tissue Content

The hypothesis that the relaxant action of many drugs on vascular and other smooth muscle is mediated by increases in intracellular cGMP, the "cGMP hypothesis," is gaining wide acceptance. While much information supporting this idea can be found in the literature, there is also a significant amount of information indicating that an elevation in the tissue content of cGMP is by itself insufficient to cause smooth muscle relaxation. The literature is reviewed with reference to the criteria that need to be fulfilled to consider cGMP as the second messenger mediating relaxation of smooth muscle by a drug; i.e., activation of guanylate cyclase, elevation of tissue content of cGMP, potentiation by phosphodiesterase inhibitors, antagonism by inhibitors of cGMP synthesis, and production of relaxation by cGMP analogues. For each criterion, key observations supporting the hypothesis are considered, followed by examples of important observations not consistent with the hypothesis. It is concluded that in some smooth muscles, for example, rat myometrium and vas deferens, cGMP is not a mediator of drug-induced relaxation. In other smooth muscles, including vascular smooth muscle, cGMP appears to play an important role in the relaxation process; but current evidence suggests that other factors are also important and that the cGMP hypothesis may need to be modified.Key words: cGMP, vascular relaxation, smooth muscle relaxation, vasodilators.

Cellular mechanism underlying hydrogen sulfide induced mouse tracheal smooth muscle relaxation: Role of BKCa

2014 ◽  
Vol 741 ◽  
pp. 55-63 ◽  
Author(s):  
Jiehong Huang ◽  
Yu-li Luo ◽  
Yuan Hao ◽  
Yi-lin Zhang ◽  
Peng-xiao Chen ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Hydrogen Sulfide ◽  
Muscle Relaxation ◽  
Cellular Mechanism ◽  
Tracheal Smooth Muscle ◽  
Smooth Muscle Relaxation

scholarly journals The role of cytoskeleton in the regulation of contractile activity in smooth muscle cells from aorta of rats

2007 ◽  
Vol 6 (1) ◽  
pp. 78-82
Author(s):  
S. V. Gousakova
Keyword(s):  
Smooth Muscle ◽  
Contractile Activity ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Aortic Smooth Muscle ◽  
Physiologically Active Substances ◽  
Cytochalasine B ◽  
Smooth Muscle Contractions ◽  
System Operating

Influence of cytoskeleton modulation by Colchicine and Cytochalasine B on contractile reactions of smooth muscle segments of rat's aorta caused by physiologically active substances, the membrane's depolarization and cells' striction was investigated by mechanographical method. Microtubules and actinic elements of the cytoskeleton were established to participate in the development of hyper-potassic and phenylephrine -induced contractions as well as in the smooth muscle relaxation induced by cAMP. Cytochalasine B suppresses both kinds of aortic smooth muscle contractions more effectively than Colchicine. Contractile reactions at isoosmotic striction are suppressed only by Cytochalasine. Efficacy of cAMP signal system operating depends on actinic cyto-skeleton integrity.

ROLE OF CYCLIC GMP IN CORONARY SMOOTH MUSCLE RELAXATION

Abstracts ◽  
1978 ◽  
pp. 793 ◽  
Author(s):  
S. Holzmann ◽  
A. Wurm ◽  
G. Pöch ◽  
W.R. Kukovetz
Keyword(s):  
Smooth Muscle ◽  
Cyclic Gmp ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Coronary Smooth Muscle
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