Effects of L-arginine analogues on vasomotion of isolated porcine coronary arteries

1995 ◽  
Vol 268 (5) ◽  
pp. H1966-H1972 ◽  
Author(s):  
R. Nakaike ◽  
H. Shimokawa ◽  
H. Yasutake ◽  
H. Sumimoto ◽  
A. Ito ◽  
...  

L-Arginine analogues have been widely used to examine the role of endothelium-derived nitric oxide (NO) in vascular responses; however, the effects of the agents on coronary vasomotion are not fully understood. In this study, we examined the effects of the analogues on vasomotion of isolated porcine coronary arteries. Strips of the porcine coronary artery were suspended for isometric tension recording in Krebs-Henseleit solution. L-Arginine analogues, N omega-nitro-L-arginine methyl ester (L-NAME, 10(-9)-10(-3) M), NG-monomethyl-L-arginine (L-NMMA, 10(-9)-10(-3) M), and NG-nitro-L-arginine (L-NNA, 10(-9)-10(-3) M), caused dose-dependent contractions, which were greater in strips with than in those without endothelium. Those endothelium-dependent contractions were almost abolished by indomethacin (10(-5) M) and FeCl2 (10(-3) M). The latter reduces prostaglandin H2 to 12-heptadecatrienoic acid, which has no vasoconstrictor effect. These results indicate that the L-arginine analogues cause endothelium-dependent contractions that are mediated by prostaglandin endoperoxides and suggest that they have properties other than simple inhibition of NO synthesis in porcine coronary arteries.

1991 ◽  
Vol 261 (3) ◽  
pp. H830-H835 ◽  
Author(s):  
C. L. Cowan ◽  
R. A. Cohen

The role of nitric oxide and guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in the endothelium-dependent relaxation of the porcine coronary artery to bradykinin was investigated by comparing relaxation and cGMP accumulation in the presence or absence of NG-monomethyl-L-arginine (L-NMMA) and methylene blue. Rings were treated with indomethacin to eliminate the effects of prostaglandins. Relaxation to bradykinin of rings contracted with the thromboxane A2 mimetic U-46619 was not affected by L-NMMA and was only minimally inhibited by methylene blue. Rings contracted with elevated potassium (25 mM) also relaxed completely to bradykinin. However, L-NMMA or methylene blue effectively inhibited relaxation to bradykinin in rings contracted with potassium. cGMP accumulation was stimulated by bradykinin and inhibited by L-NMMA or methylene blue in rings contracted with either U-46619 or potassium. These results suggest that in the absence of nitric oxide-induced cGMP accumulation, a nonprostanoid mechanism exists that is capable of completely relaxing U-46619-contracted coronary artery. This mechanism is either inhibited in or unable to relax potassium-contracted rings. These results also demonstrate that nitric oxide mediates the bradykinin-induced cGMP accumulation that is largely responsible for the relaxation during contraction with potassium.


2006 ◽  
Vol 147 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Hok Sum Leung ◽  
Xiaoqiang Yao ◽  
Fung Ping Leung ◽  
Wing Hung Ko ◽  
Zhen-Yu Chen ◽  
...  

2004 ◽  
Vol 82 (11) ◽  
pp. 993-999 ◽  
Author(s):  
Pei-Han Xu ◽  
Ming Chang ◽  
Li-Xiang Cheng ◽  
Qiang Cheng ◽  
Xiang Yan ◽  
...  

Nociceptin (NC), alias orphanin FQ, has been identified as the endogenous ligand of the opioid receptor-like 1 receptor (ORL1). The purpose of this study was to assess the effect of nociceptin on porcine coronary arteries and to investigate the mechanism of its action, if any. Rings of coronary arteries from porcine hearts were suspended in baths containing Krebs solution, and isometric tension was measured. The response to nociceptin (10–12–10–5 mol/L) was investigated in porcine coronary arterial rings and also in such rings contracted with prostaglandin F2α (PGF2α). The effects of endothelium, nitroxide (NO), methylene blue, cyclic GMP (cGMP), naloxone, [Nphe1]NC(1–13)NH2, and propranolol on nociceptin-induced relaxation were also assessed. Our study showed nociceptin relaxed the porcine coronary arterial rings and inhibited the vasocontractivity to PGF2α. The relaxing response of nociceptin in coronary arteries was significantly reduced by removal of endothelium and by the presence of L-NNA, cGMP, and [Nphe1]NC(1–13)NH2, the selective nociceptin receptor antagonist, but not by naloxone, the nonselestive opioid receptor blocker or propranolol, which blocks the adrenergic β-receptor. Our results suggest that nociceptin induces relaxation of isolated coronary artery through NO, cGMP, and ORL1.Key words: nociceptin, porcine coronary artery, NO, ORL1.


2009 ◽  
Vol 37 (4) ◽  
pp. 1011-1017 ◽  
Author(s):  
O Dagtekin ◽  
HJ Gerbershagen ◽  
E Özgür ◽  
J Gaertner ◽  
JH Fischer

This study investigated the effects of thiopental on endothelium-dependent relaxation (EDR), and especially the effects on nitric oxide-and prostacyclin-independent EDR. Fresh porcine coronary artery rings (4 mm long), were consecutively tested with and without 20 μg/ml thiopental in Krebs–Henseleit solution. Indomethacin (10 μmol/1) was used in all experiments to eliminate prostacyclin effects. Prostaglandin F2α (10 μmol/l) was used to induce contractions and bradykinin (10−10−10−5 M) was used to induce EDR. Experiments were also carried out using 300 μmol/1 N-nitro-l-arginine to block nitric oxide production and to assess the influence of thiopental on nitric oxide-and prostacyclin-independent EDR. Thiopental induced statistically significant increases in EDR at concentrations of 10−6−10−5 M bradykinin. Following nitric oxide production block, thiopental significantly reduced the relaxation response at concentrations of 10−8−10−5 M bradykinin. At a clinically relevant concentration of 20 μg/ml thiopental, a significant increase in EDR and a significant reduction in nitric oxide-and prostacyclin-independent relaxation was observed in porcine epicardial coronary arteries.


1995 ◽  
Vol 269 (5) ◽  
pp. H1672-H1678 ◽  
Author(s):  
W. Abebe ◽  
T. Hussain ◽  
H. Olanrewaju ◽  
S. J. Mustafa

In the present study, using porcine coronary artery rings in vitro, we examined the role of the nitric oxide (NO) pathway in endothelium-dependent vasorelaxant effects of the 5'-uronamide adenosine agonists, 5'-(N-ethylcarboxamido)adenosine (NECA) and 2-[p-(2-carboxyethyl)]phenylethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS-21680) as opposed to the endothelium-independent actions of the C2- and N6-substituted analogues, 2-chloroadenosine (CAD) and N6-cyclopentyladenosine (CPA). The NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 30 microM), and the NO-destroying agent, 6-anilino-5,8-quinolinedione (LY-83583, 10 microM), attenuated the relaxations of endothelium-intact but not -denuded rings to NECA and CGS-21680. The effect of L-NMMA on NECA-induced relaxation was reversed by L-arginine (100 microM), a substrate for NO synthesis. In the endothelium-intact tissues, both NECA and CGS-21680 elicited enhanced production of nitrite, a stable metabolite of NO. This was also attenuated by L-NMMA or endothelium removal. Furthermore, NECA (10 microM) induced augmentation of guanosine 3',5'-cyclic monophosphate (cGMP) production in the intact arteries, which was also inhibited by L-NMMA, LY-83583, or endothelium removal. In contrast, vasorelaxant responses generated by CAD and CPA were not altered by either L-NMMA or LY-83583. Both agents (10 microM) were also unable to alter nitrite and/or guanosine 3',5'-cyclic monophosphate (cGMP) levels of the coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Huixia Liu ◽  
Yanjing Li ◽  
Yuanming An ◽  
Peixin He ◽  
Liling Wu ◽  
...  

Objective. Hypoxia-induced sustained contraction of porcine coronary artery is endothelium-independent and mediated by PI3K/Akt/Rho kinase. Nitroglycerin (NTG) is a vasodilator used to treat angina pectoris and acute heart failure. The present study was to determine the role of NTG in hypoxia-induced endothelium-independent contraction and the underlying mechanism.Methods and Results. Organ chamber technique was used to measure the isometric vessel tension of isolated porcine coronary arteries. Protein levels of phosphorylated and total Akt were determined by western blot. A sustained contraction of porcine coronary arteries induced by hypoxia was significantly reduced by NTG but not by isoproterenol. This contraction was also inhibited by DETA NONOate, 8-Br-cGMP, which can be reversed by ODQ, and Rp-8-Br-PET-cGMPS. The restored contraction was blocked by LY294002. The reduction of Akt-p at Ser-473 by NTG, DETA NONOate, and 8-Br-cGMP was significantly inhibited by ODQ, PKG-I. The decrease in Akt-p level by NTG and 8-Br-cGMP was prevented by calyculin A but not by okadaic acid.Conclusions. These results demonstrated that the endothelium-independent sustained hypoxic vasoconstriction can be prevented by NTG and that the inhibition of PI3K/Akt signaling pathway may be involved.


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