scholarly journals Uridine adenosine tetraphosphate-induced contraction is increased in renal but not pulmonary arteries from DOCA-salt hypertensive rats

2011 ◽  
Vol 301 (2) ◽  
pp. H409-H417 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Rita C. Tostes ◽  
R. Clinton Webb
Keyword(s):  
Pulmonary Arteries ◽  
P2y Receptors ◽  
Isometric Tension ◽  
Erk Pathway ◽  
Nitric Oxide Synthase Inhibitor ◽  
Salt Hydrate ◽  
Erk Activation ◽  
Trisodium Salt ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Uridine adenosine tetraphosphate (Up4A) was reported as a novel endothelium-derived contracting factor. Up4A contains both purine and pyrimidine moieties, which activate purinergic (P2)X and P2Y receptors. However, alterations in the vasoconstrictor responses to Up4A in hypertensive states remain unclear. The present study examined the effects of Up4A on contraction of isolated renal arteries (RA) and pulmonary arteries (PA) from DOCA-salt rats using isometric tension recording. RA from DOCA-salt rats exhibited increased contraction to Up4A versus arteries from control uninephrectomized rats in the absence and presence of NG-nitro-l-arginine (nitric oxide synthase inhibitor). On the other hand, the Up4A-induced contraction in PA was similar between the two groups. Up4A-induced contraction was inhibited by suramin (nonselective P2 antagonist) but not by diinosine pentaphosphate pentasodium salt hydrate (Ip5I; P2X1 antagonist) in RA from both groups. Furthermore, 2-thiouridine 5′-triphosphate tetrasodium salt (2-ThioUTP; P2Y2 agonist)-, uridine-5′-(γ-thio)-triphosphate trisodium salt (UTPγS; P2Y2/P2Y4 agonist)-, and 5-iodouridine-5′- O-diphosphate trisodium salt (MRS 2693; P2Y6 agonist)-induced contractions were all increased in RA from DOCA-salt rats. Protein expression of P2Y2-, P2Y4-, and P2Y6 receptors in RA was similar between the two groups. In DOCA-salt RA, the enhanced Up4A-induced contraction was reduced by PD98059, an ERK pathway inhibitor, and Up4A-stimulated ERK activation was increased. These data are the first to indicate that Up4A-induced contraction is enhanced in RA from DOCA-salt rats. Enhanced P2Y receptor signaling and activation of the ERK pathway together represent a likely mechanism mediating the enhanced Up4A-induced contraction. Up4A might be of relevance in the pathophysiology of vascular tone regulation and renal dysfunction in arterial hypertension.

Alterations of endothelium and smooth muscle function in monocrotaline-induced pulmonary hypertensive arteries

2000 ◽  
Vol 279 (4) ◽  
pp. H1786-H1795 ◽  
Author(s):  
Kaoru M. Ito ◽  
Miharu Sato ◽  
Keiko Ushijima ◽  
Masaaki Nakai ◽  
Katsuaki Ito
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Artery ◽  
Single Injection ◽  
Early Stage ◽  
Pulmonary Arteries ◽  
Nitric Oxide Synthase Inhibitor ◽  
Basal Tone ◽  
Smooth Muscle Function ◽  
Synthase Inhibitor ◽  
Oxide Synthase

We examined how monocrotaline (MCT), which impairs the endothelium and causes pulmonary hypertension, altered the endothelial regulation of pulmonary artery functions. Rats were given a single injection of MCT (60 mg/kg sc). Pulmonary arteries were depolarized to −48.3 ± 2.6 and −39.8 ± 2.2 mV at 2 and 3 wk after treatment with MCT, respectively (control arteries −59.9 ± 1.9 mV). The basal tone in the resting state was only slightly elevated at 3 wk in endothelium-intact arteries. Removal of the endothelium caused further depolarization in MCT-affected arteries at 2 wk, but not at 3 wk, and greatly elevated the basal tone at 2 and 3 wk. N ω-nitro-l-arginine (200 μM), a nitric oxide synthase inhibitor, also caused depolarization in endothelium-intact arteries in both groups and elevated the basal tone of MCT-affected arteries. The relaxant responses of pulmonary arteries to ACh and A-23187 were depressed at 2 and 3 wk after MCT treatment. Thus chronic impairment of the endothelium altered the property of the pulmonary artery leading to depolarization. During the early stage of depolarization, a rise in the basal tone was offset by nitric oxide released from the injured endothelium.

Isoflurane Anesthesia Attenuates Endothelium-dependent Pulmonary Vasorelaxation by Inhibiting the Synergistic Interaction between Nitric Oxide and Prostacyclin 

1997 ◽  
Vol 86 (4) ◽  
pp. 936-944 ◽  
Author(s):  
Linda M. Gambone ◽  
Paul A. Murray ◽  
Nicholas A. Flavahan
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arteries ◽  
Inhibitory Effect ◽  
Isometric Tension ◽  
Synergistic Interaction ◽  
Nitric Oxide Synthase Inhibitor ◽  
Channel Dependent ◽  
The Individual ◽  
Synthase Inhibitor ◽  
Endothelium Dependent Relaxation

Background Endothelium-derived nitric oxide causes vasodilation in part by increasing the dilator activity of other endothelium-derived mediators, including prostacyclin and a K+ATP channel-dependent hyperpolarizing factor. Although previous studies have proposed that isoflurane (ISO) depresses endothelium-dependent vasorelaxation by inhibiting endothelium-derived nitric oxide activity, the effects of ISO on the interactions among endothelium-derived dilators have not been characterized. The aim of this study was to determine the mechanisms underlying the inhibitory effect of ISO on endothelium-dependent relaxation in canine pulmonary arteries. Specifically, the goal was to assess the effects of ISO on the individual actions and on the synergistic interactions of these endothelium-derived mediators. Methods Canine pulmonary arterial rings were suspended for isometric tension recording. The effects of 1 minimum alveolar concentration ISO (0.4 mM) on vasorelaxation responses to bradykinin, A23187, acetylcholine, cromakalim, and SIN-1 were assessed in phenylephrine-precontracted rings with and without pretreatment with a nitric oxide synthase inhibitor (N omega-nitro-L-arginine methyl ester; L-NAME), a cyclooxygenase inhibitor (indomethacin), or a K+ATP channel inhibitor (glybenclamide). Results Isofluane attenuated pulmonary vasorelaxation induced by bradykinin, A23187, and cromakalim but had no effect on relaxation induced by acetylcholine or SIN-1. Neither the nitric oxide-mediated nor the prostacyclin-mediated components of relaxation induced by bradykinin and A23187 were altered by ISO. However, ISO abolished the K+ATP-mediated component of relaxation and the K+ATP-dependent synergistic interaction between nitric oxide and prostacyclin. Conclusions These results suggest that ISO selectively attenuates endothelium-dependent relaxation in canine pulmonary arteries. It exerts its inhibitory effect by interfering with a synergistic interaction between nitric oxide and prostacyclin, possibly via an effect on K+ATP channels.

Halothane Attenuates Endothelium-dependent Pulmonary Vasorelaxant Response to Lemakalim, an Adenosine Triphosphate (ATP)-sensitive Potassium Channel Agonist

1997 ◽  
Vol 87 (3) ◽  
pp. 625-634 ◽  
Author(s):  
Sumihiko Seki ◽  
Mayumi Horibe ◽  
Paul A. Murray
Keyword(s):  
Adenosine Triphosphate ◽  
Inhibitory Effect ◽  
Isometric Tension ◽  
Maximal Response ◽  
Response Curves ◽  
Nitric Oxide Synthase Inhibitor ◽  
Pulmonary Vasodilation ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Channel Agonist

Background Lemakalim, an adenosine triphosphate (ATP)-sensitive potassium (K+(ATP)) channel agonist, causes profound pulmonary vasodilation in conscious dogs, which is attenuated during halothane anesthesia. The goal of the present study was to investigate the mechanism responsible for this attenuating effect of halothane. Methods Isolated canine pulmonary arterial rings were suspended for isometric tension recording in 25 ml organ baths. Rings with and without endothelium were contracted to 50% of their maximal response to phenylephrine, followed by the cumulative administration of lemakalim with or without exposure to halothane (0.5-1.5 minimum alveolar concentration [MAC] in dogs). Lemakalim dose-response curves were also generated in rings pretreated with the nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME); the cyclooxygenase inhibitor, indomethacin; or the K+(ATP) channel antagonist, glybenclamide. Results Compared with intact rings, the pulmonary vasorelaxant response to lemakalim was attenuated (P < 0.05) in endothelium-denuded rings. Halothane at 0.5 MAC had no effect on the vasorelaxant response to lemakalim. Halothane at 1 MAC attenuated (P < 0.05) the vasorelaxant response to lemakalim in intact rings, but not in endothelium-denuded rings. Halothane at 1.5 MAC attenuated (P < 0.05) the vasorelaxant response to lemakalim in both intact and endothelium-denuded rings. In endothelium-intact rings, indomethacin attenuated (P < 0.05) the vasorelaxant response to lemakalim, whereas L-NAME had no effect. Further, indomethacin, but not L-NAME, abolished the endothelium-dependent, halothane-induced attenuation of the lemakalim vasorelaxation response. Glybenclamide markedly attenuated (P < 0.05) lemakalim vasorelaxation at lemakalim doses less than 10(-6) M. Conclusions Lemakalim-induced pulmonary vasorelaxation involves an endothelium-dependent and vascular smooth muscle component. Further, halothane attenuates the endothelium-dependent pulmonary vasorelaxant response to lemakalim via an inhibitory effect on vasodilator metabolites of the cyclooxygenase pathway.

Effect of progesterone on the contractile response of isolated pulmonary artery in rabbits

2001 ◽  
Vol 79 (6) ◽  
pp. 545-550 ◽  
Author(s):  
Hong-Fang Li ◽  
Tian-Zhen Zheng ◽  
Wei Li ◽  
Song-Yi Qu ◽  
Chen-Lie Zhang
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Artery ◽  
Pulmonary Arteries ◽  
Isometric Tension ◽  
Krebs Solution ◽  
Prostaglandin Synthase ◽  
Intracellular Ca ◽  
Β Receptor ◽  
Synthase Inhibitor ◽  
Oxide Synthase

The purpose of this study was to assess the direct effect of progesterone on rabbit pulmonary arteries and to examine the mechanism of its action. Rings of pulmonary artery from male rabbits were suspended in organ baths containing Krebs solution, and isometric tension was measured. The response to progesterone was investigated in arterial rings contracted with noradrenaline (NA), KCl, and CaCl2. The effects of endothelium, nitric oxide(NO), prostaglandins, cyclic GMP(cGMP), and the adrenergic β-receptor on progesterone-induced relaxation were also assessed. Progesterone inhibited the vasocontractivity to NA, KCl, and CaCl2, and relaxed rabbit pulmonary artery. The relaxing response of progesterone in pulmonary artery was significantly reduced by removal of endothelium, inhibitors of nitric oxide synthase and guanylate cyclase, but not by prostaglandin synthase inhibitor and blockage of the adrenergic β-receptor. In Ca2+-free (0.1 mM EGTA) Krebs solution, progesterone inhibited NA-induced contraction that was intracellular Ca2+-dependent, but didn't affect the contraction of extracellular Ca2+-dependent component. Our results suggest that progesterone induces relaxation of isolated rabbit pulmonary arteries partially via NO and cGMP. Progesterone may also inhibit Ca2+ influx through potential-dependent calcium channels (PDCs) and Ca2+ release from intracellular stores.Key words: progesterone, pulmonary artery, Ca2+ channel, endothelium.

Developmental differences in endothelium-dependent responses in isolated ovine pulmonary arteries and veins

1993 ◽  
Vol 264 (6) ◽  
pp. H2162-H2167 ◽  
Author(s):  
R. H. Steinhorn ◽  
F. C. Morin ◽  
S. F. Gugino ◽  
E. C. Giese ◽  
J. A. Russell
Keyword(s):  
Pulmonary Veins ◽  
Age Groups ◽  
Pulmonary Arteries ◽  
Developmental Differences ◽  
Nitric Oxide Synthase Inhibitor ◽  
Prostaglandin Inhibitors ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Arteries And Veins

Despite evidence for an important role for endothelium-derived relaxing factor (EDRF) in transitional circulation, previous in vitro studies of newborn pulmonary arteries have demonstrated diminished EDRF activity when compared with arteries from older animals. We studied pulmonary arteries and veins isolated from early newborn and juvenile sheep using standard tissue bath techniques. Incubation of vessels with the nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NNA) constricted veins but not arteries from both age groups. Further studies using preconstricted vessels revealed that arteries relaxed to acetylcholine (ACh), with significantly greater responses observed in juvenile arteries. Veins from both age groups contracted to ACh. Pretreatment with prostaglandin inhibitors (indomethacin and SQ 29,548) diminished ACh relaxations in pulmonary arteries from both age groups, greatly enhanced relaxations to ACh in newborn pulmonary veins, and depressed contractions in juvenile pulmonary veins. Removal of endothelium mechanically or functionally with prostaglandin inhibitors and L-NNA eliminated relaxations to ACh in pulmonary arteries from both age groups and resulted in contractions in veins. We conclude that isolated pulmonary veins from newborn sheep exhibit both baseline and stimulated release of EDRF, and we speculate that these venous responses may be important in the transitional pulmonary circulation.

Glomerular and tubular interactions between renal adrenergic activity and nitric oxide

1995 ◽  
Vol 268 (6) ◽  
pp. F1004-F1008 ◽  
Author(s):  
F. B. Gabbai ◽  
S. C. Thomson ◽  
O. Peterson ◽  
L. Wead ◽  
K. Malvey ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Glomerular Filtration ◽  
Renal Nerves ◽  
Ang Ii ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adrenergic Activity ◽  
Single Nephron ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Endothelium-dependent nitric oxide (EDNO) exerts control over the processes of glomerular filtration and tubular reabsorption. The importance of the renal nerves to the tonic influence of EDNO in the glomerular microcirculation and proximal tubule was tested by renal micropuncture in euvolemic adult male Munich-Wistar rats. The physical determinants of glomerular filtration and proximal reabsorption were assessed before and during administration of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in control animals and in animals 5–9 days after either ipsilateral surgical renal denervation (DNX) or after either sham surgery (SHX). L-NMMA caused single-nephron glomerular filtration rate to decline in control and SHX animals but not in DNX rats. L-NMMA caused a reduction in proximal reabsorption in control and SHX rats, which was prevented by prior DNX. DNX did not alter urinary guanosine 3',5'-cyclic monophosphate excretion, and, although DNX upregulates glomerular angiotensin II (ANG II) receptors, prior DNX did not alter intrarenal ANG II content as evaluated by radioimmunoassay. Some component of renal adrenergic activity is required for the full expression of the glomerular and tubular effects of blockade of nitric oxide synthase.

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