scholarly journals Nitric oxide pathway-mediated relaxant effect of PPAR (Peracisome proliferator activated receptor)-Gamma agonist in the guinea-pig isolated trachea.

2020 ◽  
Vol 27 (09) ◽  
pp. 1855-1861
Author(s):  
Naila Abrar ◽  
Ayesha Janjua ◽  
Sarwat Jahan ◽  
Zarafshan Badar ◽  
Asma Khan ◽  
...  

Objectives: This study focuses on the role of the mediator of smooth muscles i.e. nitric oxide in the effect of rosiglitazone on the relaxation of contractions in guinea pig trachea induced by histamine. Study Design: Experimental Study. Setting: Department of Pharmacology, Army Medical College, Rawalpindi. Period: 1st December 2018 till 14th December 2018. Material & Methods: The activity of the trachealis mucle of the guinea pigs was noted by the use of oxygenated solution of Krebs-Henseleit. The contractions were noted with rosiglitazone alone as well as in presence of an ester of L-nitro-arginine-methyl, which can antagonize the activity of NO. The activity was measured by the use of an isometric force displacement transducer and was then recorded on an oscillograph with four channels. Results: The ester L-nitro-arginine-methyl was able to reduce the relaxant effect of rosiglitazone on the contractions induced by histamine. Conclusion: It can be suggested that the relaxation induced by rosiglitazone is mediated in part through NO.

1998 ◽  
Vol 7 (1) ◽  
pp. 35-40 ◽  
Author(s):  
G. Sadeghi-Hashjin ◽  
P. A. J. Henricks ◽  
G. Folkerts ◽  
T. Muis ◽  
J. Garssen ◽  
...  

The lucigenin-dependent chemiluminescence generation by guinea-pig isolated tracheal two rings preparations was studied. Tracheal preparations stimulated with phorbol myristate acetate (PMA) or opsonized zymosan generated chemiluminescence. The total amount of chemiluminescence generated in 120 min was 754 ± 63 mV × min for PMA and 4832 ±396 mV × min for zymosan. Generation of chemiluminescence was decreased by more than 50% when the tissues were co-incubated with superoxide dismutase (100 U/ml). Also, addition of direct donors of nitric oxide diminished chemiluminescence generation by zymosan-activated tracheal rings significantly by about 50%. However, the presence of the precursor or of inhibitors of nitric oxide synthase did not influence zymosan-induced chemiluminescence. Removal of the epithelial layer from tracheal rings caused an approximately 90% decrease in chemiluminescence response. However, isolated epithelial cell suspensions did not generate chemiluminescence. Histologic examination showed that the number of eosinophils in the tracheal tissue was reduced from 56 ± 7 to 18 ± 8 per mm basal membrane when the epithelial layer was removed. These results indicated that (1) superoxide anion formation can take place in the guinea-pig trachea, (2) eosinophils in the epithelial and submucosal layers of guinea-pig trachea are likely candidates for superoxide generation although other cell types can also be involved, and (3) besides relaxing airway smooth muscle, nitric oxide donors may also affect superoxide in the airways.


1995 ◽  
Vol 268 (4) ◽  
pp. H1586-H1592 ◽  
Author(s):  
Y. Gao ◽  
H. Zhou ◽  
J. U. Raj

Endothelium-derived nitric oxide (EDNO) modulates fetal pulmonary vasoactivity. The role of EDNO in regulation of vasomotor tone in fetal pulmonary arteries vs. that in veins is not known. We have investigated the role of EDNO in the responses of pulmonary arteries and veins of full-term fetal lambs. Fourth-generation pulmonary arterial and venous rings were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O2-5% CO2 at 37 degrees C), and their isometric force was measured. N omega-nitro-L-arginine had no effect on the resting tension of pulmonary arteries with endothelium but caused contraction of pulmonary veins with endothelium. The basal level of intracellular guanosine 3',5'-cyclic monophosphate (cGMP) of pulmonary veins with endothelium was higher than that of arteries with endothelium. In pulmonary arteries, bradykinin, but not acetylcholine, induced endothelium-dependent relaxation and an increase in cGMP content. In pulmonary veins, acetylcholine, but not bradykinin, induced endothelium-dependent relaxation and an increase in cGMP content. Agonist-induced maximal relaxation and increases in cGMP content were smaller in pulmonary arteries than in veins. All these endothelium-dependent responses were abolished by N omega-nitro-L-arginine. In tissues without endothelium, nitric oxide induced significantly less relaxation and less increase in cGMP content in pulmonary arteries than in pulmonary veins. All vessels relaxed similarly to 8-bromoguanosine 3',5'-cyclic monophosphate. Our data suggest that the role of EDNO in modulating tone differs between pulmonary arteries and veins in full-term fetal lambs.(ABSTRACT TRUNCATED AT 250 WORDS)


2013 ◽  
Vol 25 (2) ◽  
pp. e114-e126 ◽  
Author(s):  
C. Giaroni ◽  
S. Marchet ◽  
E. Carpanese ◽  
V. Prandoni ◽  
R. Oldrini ◽  
...  

2000 ◽  
Vol 78 (9) ◽  
pp. 729-736 ◽  
Author(s):  
Mayumi Mori ◽  
Hiromi Tsushima

To elucidate the possible role of Rho A/Rho-kinase on lysophosphatidic acid (LPA)-induced contraction in intact guinea-pig ileal smooth muscle, we examined effects of pretreatment with a specific inhibitor of Rho-kinase (Y-27632) on the LPA-induced contraction and MLC20 phosphorylation. In addition, we investigated whether LPA actually elicits an activation of Rho A by studying subcellular distribution of Rho A in unstimulated and stimulated smooth muscles by LPA. LPA induced a less intense, but sustained, contraction compared with ACh, and was accompanied by significant increases in MLC20 phosphorylation. The effects of LPA on tension and MLC20 phosphorylation were inhibited by Y-27632. The ACh-induced contraction, but not increases in MLC20 phosphorylation, was partially inhibited by Y-27632. High K+-induced contraction was unaffected by the inhibitor. LPA stimulated translocation of Rho A from the cytosol to the membrane fraction of the muscle. Translocation of Rho A was also induced by ACh and high K+. These results suggest that LPA-induced contraction of intact ileal smooth muscle is dominated through activation of Rho A and Rho-kinase and subsequent increases in MLC20 phosphorylation.Key words: lysophosphatidic acid, Rho, Rho-kinase, ileal smooth muscle.


2003 ◽  
Vol 285 (4) ◽  
pp. G747-G753 ◽  
Author(s):  
Catalina Caballero-Alomar ◽  
Carmen Santos ◽  
Diego Lopez ◽  
M. Teresa Mitjavila ◽  
Pere Puig-Parellada

We examined in vitro the source and role of basal nitric oxide (NO) in proximal segments of guinea pig taenia caeci in nonadrenergic, noncholinergic (NANC) conditions. Using electron paramagnetic resonance (EPR), we measured the effect of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 10–4 M), the neuronal blocker tetrodotoxin (TTX, 10–6 M), or both on spontaneous contractions and on the production of basal NO. Both l-NAME and TTX, when tested alone, increased the amplitude and frequency of contractions. NO production was abolished by l-NAME and was inhibited by 38% by TTX. When tested together, l-NAME in the presence of TTX or TTX in the presence of l-NAME had no further effect on the amplitude or frequency of spontaneous contractions, and the NO production was inhibited. These findings suggest that basal NO consists of TTX-sensitive and TTX-resistant components. The TTX-sensitive NO has an inhibitory effect on spontaneous contractions; the role of TTX-resistant NO is unknown.


Author(s):  
MichelR. Briejer ◽  
LouisM.A. Akkermans ◽  
AnnL. Meulemans ◽  
RomainA. Lefebvre ◽  
JanA.J. Schuurkes

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