Involvement of gap junctions in bradykinin-induced relaxation of bovine pulmonary supernumerary arteries before and after inhibition of nitric oxide/guanylate cyclase

2002 ◽  
Vol 103 (6) ◽  
pp. 553-557 ◽  
Author(s):  
A. TRACEY ◽  
A. MACDONALD ◽  
A.M. SHAW
Keyword(s):  
Nitric Oxide ◽  
Gap Junctions ◽  
Guanylate Cyclase ◽  
Response Curve ◽  
Soluble Guanylate Cyclase ◽  
Rightward Shift ◽  
Before And After ◽  
Synthase Inhibitor ◽  
Gap Junction Inhibitor ◽  
Concentration Response Curve

This study evaluated the possible contribution of gap junctions to the nitric oxide (NO)- and endothelium-derived hyperpolarizing factor (EDHF)-mediated responses elicited by bradykinin in bovine pulmonary supernumerary arteries. In artery rings with an intact endothelium and treated with the cyclo-oxygenase inhibitor indomethacin (10μM), bradykinin (100pM–1μM) produced a concentration-dependent relaxation [-logEC50 (pEC50), 9.6±0.2; maximum relaxation (Rmax), 89.7±14.8%; n = 6]. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 100μM) and the NO scavenger hydroxocobalamin (200μM) each produced a rightward shift in the bradykinin concentration–response curve [pEC50: L-NAME, 8.9±0.1 (n = 6; P<0.01); hydroxocobalamin, 8.3±0.2, (n = 6; P<0.001)]. However, the soluble guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; 10μM) did not significantly alter the response to bradykinin (pEC50 9.4±0.2; n = 9). The gap junction inhibitor carbenoxolone (100μM) did not affect the relaxation produced by bradykinin (pEC50, 9.7±0.1; Rmax, 100±3.2%; n = 6), but it significantly depressed Rmax when L-NAME, hydroxocobalamin or ODQ was present. Further, carbenoxolone produced a rightward shift in the bradykinin concentration–response curve in the presence of ODQ (8.4±0.1; n = 6, P<0.01). The data suggest that, in bovine pulmonary supernumerary arteries, gap junctions may, in part, facilitate the EDHF-mediated response, but not the NO-mediated response, to bradykinin. However, the additional involvement of an unidentified endothelial relaxing factor cannot be excluded.

Relationship between nitric oxide and opioids in hypoxia-induced pial artery vasodilation

1996 ◽  
Vol 270 (3) ◽  
pp. H869-H874 ◽  
Author(s):  
M. J. Wilderman ◽  
W. M. Armstead
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylate Cyclase ◽  
No Synthase ◽  
Pial Artery ◽  
Biochemical Effects ◽  
M 10 ◽  
Before And After ◽  
Synthase Inhibitor ◽  
Ly 83583 ◽  
The Relationship

It has previously been observed that nitric oxide (NO) and the opioids Met- and Leu-enkephalin contribute to hypoxia-induced pial artery dilation in the newborn pig. The present study was designed to investigate the relationship between NO and opioids in hypoxic pial dilation. Piglets equipped with closed cranial windows were used to measure pial artery diameter and collect cortical periarachnoid cerebrospinal fluid (CSF) for assay of opioids. Sodium nitroprusside (SNP; 10(-8) and 10(-6) M) elicited pial dilation that was blunted by the soluble guanylate cyclase inhibitor LY-83583 (10(-5) M; 10 +/- 1 and 23 +/- 1 vs. 3 +/- 1 and 7 +/- 1% for 10(-8) and 10(-6) M SNP before and after LY-83583, respectively). SNP-induced dilation was accompanied by increased CSF Met-enkephalin, and coadministration of LY-83583 with SNP blocked these increases in CSF opioid concentration (1,144 +/- 59, 2,215 +/- 165, and 3,413 +/- 168 vs. 1,023 +/- 16, 1,040 +/- 18, and 1,059 +/- 29 pg/ml for control and 10(-8) and 10(-6) M SNP before and after LY-83583, respectively). SNP-induced release of CSF Leuenkephalin was also blocked by LY-83583. Similar blunted vascular and biochemical effects of SNP were observed with coadministration of the purported guanosine 3', 5'-cyclic monophosphate (cGMP) antagonist, the phosphorothioate analogue of 8-bromo-cGMP (BrcGMP) [(R)-p-BrcGMP[S]; 10(-5) M]. The cGMP analogue, BrcGMP, elicited dilation that was also accompanied by increased CSF Met- and Leu-enkephalin. Vascular and biochemical effects of BrcGMP were blunted by (R)-p-cGMP[S] and unchanged by LY-83583. Hypoxia-induced pial artery dilation was attenuated by N omega-nitro-L-arginine (L-NNA; 10(-6) M), an NO synthase inhibitor (25 +/- 2 vs. 14 +/- 1%). Hypoxic pial dilation was accompanied by increased CSF Met-enkephalin, and these increases were attenuated by L-NNA (1,137 +/- 60 and 3,491 +/- 133 vs. 927 +/- 25 and 2,052 +/- 160 pg/ml for control and hypoxia before and after L-NNA, respectively). Hypoxia also increased CSF Leuenkephalin, and these CSF changes were similarly attenuated by L-NNA. These data show that cGMP increases CSF Met- and Leu-enkephalin. Furthermore, these data suggest that NO contributes to hypoxic dilation, at least in part, via formation of cGMP and the subsequent release of opioids.

Vasoactivity of the gasotransmitters hydrogen sulfide and carbon monoxide in the chicken ductus arteriosus

2011 ◽  
Vol 301 (4) ◽  
pp. R1186-R1198 ◽  
Author(s):  
Saskia van der Sterren ◽  
Pamela Kleikers ◽  
Luc J. I. Zimmermann ◽  
Eduardo Villamor
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Guanylate Cyclase ◽  
Vascular Tone ◽  
Soluble Guanylate Cyclase ◽  
Ductus Arteriosus ◽  
No Synthase ◽  
Mechanical Responses ◽  
Synthase Inhibitor

Besides nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) is a third gaseous messenger that may play a role in controlling vascular tone and has been proposed to serve as an O2 sensor. However, whether H2S is vasoactive in the ductus arteriosus (DA) has not yet been studied. We investigated, using wire myography, the mechanical responses induced by Na2S (1 μM–1 mM), which forms H2S and HS− in solution, and by authentic CO (0.1 μM-0.1 mM) in DA rings from 19-day chicken embryos. Na2S elicited a 100% relaxation (pD2 4.02) of 21% O2-contracted and a 50.3% relaxation of 62.5 mM KCl-contracted DA rings. Na2S-induced relaxation was not affected by presence of the NO synthase inhibitor l-NAME, the soluble guanylate cyclase (sGC) inhibitor ODQ, or the K+ channel inhibitors tetraethylammonium (TEA; nonselective), 4-aminopyridine (4-AP, KV), glibenclamide (KATP), iberiotoxin (BKCa), TRAM-34 (IKCa), and apamin (SKCa). CO also relaxed O2-contracted (60.8% relaxation) and KCl-contracted (18.6% relaxation) DA rings. CO-induced relaxation was impaired by ODQ, TEA, and 4-AP (but not by l-NAME, glibenclamide, iberiotoxin, TRAM-34 or apamin), suggesting the involvement of sGC and KV channel stimulation. The presence of inhibitors of H2S or CO synthesis as well as the H2S precursor l-cysteine or the CO precursor hemin did not significantly affect the response of the DA to changes in O2 tension. Endothelium-dependent and -independent relaxations were also unaffected. In conclusion, our results indicate that the gasotransmitters H2S and CO are vasoactive in the chicken DA but they do not suggest an important role for endogenous H2S or CO in the control of chicken ductal reactivity.

Nitric oxide-independent stimulation of soluble guanylate cyclase reduces organ damage in experimental low-renin and high-renin models

2010 ◽  
Vol 28 (8) ◽  
pp. 1666-1675 ◽  
Author(s):  
Yuliya Sharkovska ◽  
Philipp Kalk ◽  
Bettina Lawrenz ◽  
Michael Godes ◽  
Linda Sarah Hoffmann ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Organ Damage ◽  
Stimulation Of

YC-1, a nitric oxide-independent activator of soluble guanylate cyclase, inhibits platelet-rich thrombosis in mice

1997 ◽  
Vol 320 (2-3) ◽  
pp. 161-166 ◽  
Author(s):  
Che-Ming Teng ◽  
Chin-Chung Wu ◽  
Feng-Nien Ko ◽  
Fang-Yu Lee ◽  
Sheng-Chu Kuo
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase

O14. Functional knockout of the soluble guanylate cyclase alpha 1 subunit leads to gender-specific hypertension while retaining sensitivity to nitric oxide

Nitric Oxide ◽  
2006 ◽  
Vol 14 (4) ◽  
pp. 4-5
Author(s):  
Patrick Yves Sips ◽  
Emmanuel Buys ◽  
Elke Rogge ◽  
Sofie Nimmegeers ◽  
Mieke Dewerchin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Gender Specific

scholarly journals Differential synergy with nitric oxide across a panel of soluble guanylate cyclase stimulators

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Kimberly Long ◽  
Kim Tang ◽  
Renee Sarno ◽  
Rob Solinga ◽  
Jaime Masferrer
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase

scholarly journals Butyl Isocyanide as a Probe of the Activation Mechanism of Soluble Guanylate Cyclase

2007 ◽  
Vol 282 (49) ◽  
pp. 35741-35748 ◽  
Author(s):  
Emily R. Derbyshire ◽  
Michael A. Marletta
Keyword(s):  
Nitric Oxide ◽  
Binding Site ◽  
Guanylate Cyclase ◽  
Electronic Absorption ◽  
Soluble Guanylate Cyclase ◽  
Activation Mechanism ◽  
Activation Process ◽  
Absorbance Maximum ◽  
No Activation ◽  
Allosteric Activator

Nitric oxide (NO) is a physiologically relevant activator of the hemoprotein soluble guanylate cyclase (sGC). In the presence of NO, sGC is activated several hundredfold above the basal level by a mechanism that remains to be elucidated. The heme ligand n-butyl isocyanide (BIC) was used to probe the mechanism of NO activation of sGC. Electronic absorption spectroscopy was used to show that BIC binds to the sGC heme, forming a 6-coordinate complex with an absorbance maximum at 429 nm. BIC activates sGC 2-5-fold, and synergizes with the allosteric activator YC-1, to activate the enzyme 15-25-fold. YC-1 activates the sGC-BIC complex, and leads to an increase in both the Vmax and Km. BIC was also used to probe the mechanism of NO activation. The activity of the sGC-BIC complex increases 15-fold in the presence of NO, without displacing BIC at the heme, which is consistent with previous reports that proposed the involvement of a non-heme NO binding site in the activation process.

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