Enhanced β-receptor-mediated vasorelaxation in hypoxic porcine coronary artery

1999 ◽  
Vol 277 (4) ◽  
pp. H1447-H1452 ◽  
Author(s):  
Satoru Fukuda ◽  
Takashi Toriumi ◽  
Hui Xu ◽  
Hidenori Kinoshita ◽  
Hironobu Nishimaki ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Coronary Arteries ◽  
Response Curve ◽  
Dibutyryl Camp ◽  
Camp Content ◽  
Porcine Coronary Artery ◽  
Vasodilatory Response ◽  
High Concentrations ◽  
Β Receptor ◽  
Concentration Response Curve

To investigate the β-adrenoceptor-mediated responses in hypoxic coronary arteries, we studied the effect of isoproterenol (Iso) on isolated porcine coronary arteries contracted with endothelin-1 in media aerated with 0, 5, 7.5, and 95% O2. The concentration-response curve of Iso was significantly shifted to the left by hypoxia (0 and 5% O2). In oxygenated and hypoxic arteries, 3 × 10−8, 10−6, and 10−5 M Iso significantly increased the contents of cAMP. However, there was no difference in the increases of cAMP content induced by 3 × 10−8 M Iso between oxygenated and hypoxic arteries. The content of cAMP induced by high concentrations of Iso (10−6and 10−5 M) was significantly larger in hypoxic than in oxygenated arteries. Furthermore, the potentiation by hypoxia of the Iso-induced vasorelaxation was inhibited by glibenclamide and depolarization by KCl, but not by removal of endothelium and indomethacin. The vasodilatory response to forskolin and dibutyryl cAMP was unaffected by hypoxia. We conclude that activation of the ATP-sensitive K+ channel may account for the potentiation of the response to Iso in hypoxic coronary arteries.

The relaxant effect of nociceptin on porcine coronary arterial ring segments

2004 ◽  
Vol 82 (11) ◽  
pp. 993-999 ◽  
Author(s):  
Pei-Han Xu ◽  
Ming Chang ◽  
Li-Xiang Cheng ◽  
Qiang Cheng ◽  
Xiang Yan ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Opioid Receptor ◽  
Coronary Arteries ◽  
Isometric Tension ◽  
Orphanin Fq ◽  
Relaxant Effect ◽  
Porcine Coronary Artery ◽  
Prostaglandin F ◽  
Key Words Nociceptin ◽  
Β Receptor

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.

Pertussis toxin-sensitive G proteins in regenerated endothelial cells of porcine coronary artery

1994 ◽  
Vol 267 (3) ◽  
pp. H979-H981 ◽  
Author(s):  
T. Shibano ◽  
J. Codina ◽  
L. Birnbaumer ◽  
P. M. Vanhoutte
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
G Proteins ◽  
Coronary Arteries ◽  
Pertussis Toxin ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
High Cholesterol Diet ◽  
Porcine Coronary Artery ◽  
Yorkshire Pigs

Endothelium-dependent, pertussis toxin-sensitive relaxations are impaired selectively after regeneration of endothelial cells following balloon denudation of the porcine coronary artery. The present study was designed to examine the hypothesis that there is a difference in G proteins modified by pertussis toxin between regenerated and intact endothelial cells. Yorkshire pigs, fed a high-cholesterol diet, underwent balloon denudation of the endothelium of the left anterior descending coronary arteries (LAD). Four weeks after the denudation the animals were killed to detect G proteins by ADP ribosylation catalyzed with pertussis toxin and [32P]NAD, separated on a urea gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In membrane fractions of endothelial cells obtained from previously denuded LAD, G alpha i-1/G alpha i-3 (41 kDa) and G alpha 1-2 (40 kDa) proteins were labeled. The two bands revealed on the gel were the same as those obtained from intact left circumflex coronary arteries (LCX). However, the intensity of the bands was less prominent in the LAD than the LCX. These results suggest that either a decreased amount or a reduced functionality of Gi proteins in the regenerated endothelial cells may account for the impairment in the pertussis toxin-sensitive relaxations after balloon injury of coronary arteries in the pigs.

Inhibitors of cyclooxygenase augment serotonergic responsiveness in canine coronary arteries

1988 ◽  
Vol 255 (5) ◽  
pp. H1032-H1035
Author(s):  
G. Blaise ◽  
A. Iqbal ◽  
P. M. Vanhoutte
Keyword(s):  
Coronary Arteries ◽  
Response Curve ◽  
Coronary Smooth Muscle ◽  
Prostaglandin F2 Alpha ◽  
Secondary Relaxations ◽  
Canine Coronary Artery ◽  
Higher Doses ◽  
Large Coronary Arteries ◽  
Concentration Response Curve

Experiments were designed to determine the role of products of cyclooxygenase in contractions of coronary smooth muscle evoked by serotonin. Rings of canine coronary artery without endothelium were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Serotonin caused concentration-dependent contractions followed by secondary relaxations at higher doses. Indomethacin and meclofenamate augmented both the contraction and the relaxation. Indomethacin did not affect contractions evoked by increasing concentrations of either phenylephrine, prostaglandin F2 alpha, or potassium chloride. Propranolol did not affect the concentration-response curve to serotonin under control conditions; it prevented the facilitated contraction to the monoamine but not the augmented secondary relaxation caused by the inhibitors of cyclooxygenase. These results suggest that endogenous prostanoids simultaneously inhibit the contractile process and brake relaxations induced by higher concentrations of serotonin. As a consequence, inhibitors of prostanoid formation facilitate the vasospastic component of the response to the monoamine in large coronary arteries. For unknown reasons, propranolol prevents this facilitation.

PLATELETS, ENDOTHELIUM AND VASOSPASM

1987 ◽  
Author(s):  
Paul M Vanhoutte
Keyword(s):  
Coronary Artery ◽  
Blood Vessels ◽  
Coronary Arteries ◽  
Adenine Nucleotides ◽  
Platelet Activating Factor ◽  
Protective Role ◽  
Human Platelets ◽  
Porcine Coronary Artery ◽  
Paf Antagonists ◽  
Endothelium Dependent Relaxation

The endothelium can secrete both relaxing and contracting substances. One of the most powerful stimuli to the release of the former are thrombin and aggregating platelets. This contributes to the protective role of the endothelium against inappropriate intraluminal platelet aggregation and coagulation in blood vessels with an intact intima. Thrombin-induced, endothelium-dependent relaxations have been obtained in isolated arteries of different species, including humans. Endothelium-dependent relaxations can be evoked by autologous platelets in isolated blood vessels of the dog, pig and rat; they can be obtained in canine coronary arteries with human platelets. The major platelet-products involved in these endothelium-dependent relaxations are 5-hydroxytryptamine (serotonin) and the adenine nucleotides. Although platelet-activating factor (PAF) can evoke endothelium-dependent relaxation it only does so at concentrations much higher than those occurring under physiological conditions; since the relaxations are not prevented by PAF-antagonists, they are non-specific in nature.The receptor mediating the endothelium-dependent relaxations to serotonin released from the aggregating platelets can be subtyped as a S1~(5HT1) serotonergic receptor;those mediating the response to the adenine nucleotides as P2y-purinergic receptors. In the absence of the endothelium aggregating platelets cause contractions of vascular smooth muscle; these are mediated by a mixture of S1-like and S2~serotoner-gic receptors in coronary arteriesof the dog, and by S2-serotonergic receptors in those of the pig. Thus, in the porcine coronary artery, the S2-serotonergic antagonist ketanserin markedly enhances the platelet-induced endothelium-dependent relaxation. After previous (four weeks) injury, the regenerated endothelium of the porcine coronary artery loses the ability to respond to serotonin,and is unable to prevent the constrictionsevoked by aggregating platelets. The endothelium-dependent relaxations of porcine coronary arteries evoked by aggregating platelets are potentiated by chronic treatmentof the donor animals with cod liver oil. These studies emphasize the protective roleof the endothelial cells against the vasoconstriction (vasospasm) induced by aggregating platelets. This role is depressed after previous injury, and can be facilitatedby dietary adj ustments.

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 ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Isometric Tension ◽  
Vascular Responses ◽  
Porcine Coronary Artery ◽  
Coronary Vasomotion ◽  
Vasoconstrictor Effect ◽  
Dose Dependent

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.

Existence of two types of postjunctional α-adrenoceptors in the isolated canine internal carotid artery

1988 ◽  
Vol 66 (5) ◽  
pp. 655-659 ◽  
Author(s):  
Yasuaki Kawai ◽  
Shigeaki Kobayashi ◽  
Toshio Ohhashi
Keyword(s):  
Response Curve ◽  
Carotid Arteries ◽  
Internal Carotid ◽  
The Other ◽  
Low Concentrations ◽  
Selective Agonists ◽  
High Concentrations ◽  
The Right ◽  
Internal Carotid Arteries ◽  
Concentration Response Curve

The pharmacological characteristics of postjunctional α-adrenoceptors in isolated canine internal carotid arteries were investigated by the use of selective agonists and antagonists for α1 and α2-adrenoceptors. Norepinephrine, phenylephrine, and xylazine caused concentration-dependent contractions in the helical strips. The contraction induced by 10−4 M xylazine was significantly smaller than that produced by 10−4 M norepinephrine or 10−4 M phenylephrine. The contraction induced by 10−4 M phenylephrine was almost the same value as that induced by 10−4 M norepinephrine. Phentolamine (10−8 and 10−7 M) caused a parallel shift to the right of the concentration–response curve to norepinephrine. The contractile responses to low concentrations of norepinephrine were significantly suppressed by pretreatment with an α2-antagonist such as yohimbine (10−9 and 10−8 M) or DG 5128(10−7 and 10−6 M). On the other hand, the responses to higher concentrations of norepinephrine were mainly reduced by low concentrations of an α1-antagonist, prazosin (3 × 10−10 and 3 × 10−9 M). These results suggest that both α1- and α2-adrenoceptors are located on the plasma membrane of smooth muscle cells in canine internal carotid arteries and that the norepinephrine-induced contractions at low and high concentrations are mainly mediated by activation of α2- and α1-adrenoceptors, respectively.

Effects of Thiopental on Endothelium-Dependent Relaxation in Porcine Coronary Arteries

2009 ◽  
Vol 37 (4) ◽  
pp. 1011-1017 ◽  
Author(s):  
O Dagtekin ◽  
HJ Gerbershagen ◽  
E Özgür ◽  
J Gaertner ◽  
JH Fischer
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Relaxation Response ◽  
Nitric Oxide Production ◽  
Porcine Coronary Artery ◽  
Relevant Concentration ◽  
Oxide Production ◽  
Prostaglandin F ◽  
Endothelium Dependent Relaxation

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.

scholarly journals Hypoxic vasodilation in porcine coronary artery is preferentially inhibited by organ culture

2001 ◽  
Vol 281 (1) ◽  
pp. C24-C32 ◽  
Author(s):  
George D. Thorne ◽  
Shunichi Shimizu ◽  
Richard J. Paul
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Vascular Smooth Muscle ◽  
Organ Culture ◽  
Sodium Nitroprusside ◽  
Coronary Arteries ◽  
Calcium Concentration ◽  
Acute Hypoxia ◽  
Porcine Coronary Artery ◽  
Hypoxic Vasodilation

Hypoxia (95% N2-5% CO2) elicits an endothelium-independent relaxation (45–80%) in freshly dissected porcine coronary arteries. Paired artery rings cultured at 37°C in sterile DMEM (pH ∼7.4) for 24 h contracted normally to KCl or 1 μM U-46619. However, relaxation in response to hypoxia was sharply attenuated compared with control (fresh arteries or those stored at 4°C for 24 h). Hypoxic vasorelaxation in organ cultured vessels was reduced at both high and low stimulation, indicating that both Ca2+-independent and Ca2+-dependent components are altered. In contrast, relaxation to G-kinase (sodium nitroprusside) or A-kinase (forskolin and isoproterenol) activation was not significantly affected by organ culture. Additionally, there was no difference in relaxation after washout of the stimulus, indicating that the inhibition is specific to acute hypoxia-induced relaxation. Simultaneous force and intracellular calcium concentration ([Ca2+]i) measurements indicate the reduction in [Ca2+]i concomitant with hypoxia at low stimulus levels in these tissue is abolished by culture. Our results indicate that organ culture at 37°C specifically attenuates hypoxic relaxation in vascular smooth muscle by altering dynamics of [Ca2+]i handling and decreasing a Ca2+-independent component of relaxation. Thus organ culture can be a novel tool for investigating the mechanisms of hypoxia-induced vasodilation.

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