scholarly journals Role of Phospholipases A2 in Vascular Relaxation and Sympatholytic Effects of Five Australian Brown Snake, Pseudonaja spp., Venoms in Rat Isolated Tissues

2021 ◽  
Vol 12 ◽  
Author(s):  
Nhi Thuc Vuong ◽  
Timothy N. W. Jackson ◽  
Christine E. Wright
Keyword(s):  
Sympathetic Nerve ◽  
Mesenteric Arteries ◽  
Right Atrial ◽  
Phospholipases A2 ◽  
Life Threatening ◽  
Left And Right ◽  
Isolated Tissues ◽  
Right Atria ◽  
Phospholipases A

Human envenoming by Australian brown snakes (Pseudonaja spp.) may result in potentially life-threatening hypotension and subsequent cardiovascular collapse. There have been relatively few studies of the cardiovascular and sympathetic effects of Pseudonaja spp. venoms. In this study, we have examined the effects of venom from five brown snake species—P. affinis, aspidorhyncha, inframacula, nuchalis, and textilis—on cardiac inotropic and chronotropic responses, vascular tone, and sympathetic nerve-induced vascular contractions in rat isolated tissues. The role of phospholipases A2 (PLA2s) in venom-induced effects was assessed with the sPLA2 inhibitor varespladib. In rat isolated left and right atria, there were no physiologically relevant effects of Pseudonaja venoms (0.1–30 µg/ml) on left atrial force of contraction (inotropy) or right atrial rate (chronotropy). In contrast, in isolated small mesenteric arteries precontracted with a thromboxane mimetic, each of the five brown snake venoms (at 30 µg/ml) caused marked vasorelaxation (−60 to –90% of contractile tone). Pretreatment with varespladib (1 µM) significantly inhibited the vasorelaxation caused by P. aspidorhyncha, P. nuchalis, and P. textilis venoms. Electrically induced sympathetic nerve-mediated contractions of mesenteric arteries were significantly attenuated by only P. textilis, and P. affinis venoms (30 µg/ml) and these sympatholytic effects were inhibited by varespladib (1 µM). Based on their inhibition with the sPLA2 inhibitor varespladib, we conclude that PLA2 toxins in P. aspidorhyncha, P. nuchalis, and P. textilis venoms are involved in brown snake venom-induced vasorelaxation and the sympatholytic effects of P. affinis, and P. textilis venoms. Our study supports the promising potential role of varespladib as an initial (pre-referral) and/or adjunct (in combination with antivenom) therapeutic agent for brown snake envenoming.

scholarly journals Changes in left and right atrial size after cardioversion of atrial fibrillation: Role of mitral valve disease

1993 ◽  
Vol 22 (6) ◽  
pp. 1666-1672 ◽  
Author(s):  
A.T.Marcel Gosselink ◽  
Harry J.G.M. Crijns ◽  
Hans P.M. Hamer ◽  
Hans Hillege ◽  
Kong I. Lie
Keyword(s):  
Atrial Fibrillation ◽  
Mitral Valve ◽  
Mitral Valve Disease ◽  
Valve Disease ◽  
Right Atrial ◽  
Atrial Size ◽  
Left And Right

Distinct shear-induced Ca2+ signaling in the left and right atrial myocytes: Role of P2 receptor context

2020 ◽  
Vol 143 ◽  
pp. 38-50 ◽  
Author(s):  
Qui Anh Le ◽  
Joon-Chul Kim ◽  
Kyeong-Hee Kim ◽  
Anh Thi Van Vu ◽  
Sun-Hee Woo
Keyword(s):  
Right Atrial ◽  
P2 Receptor ◽  
Atrial Myocytes ◽  
Left And Right

Presence and functional role of the rapidly activating delayed rectifier K+ current in left and right atria of adult mice

2010 ◽  
Vol 649 (1-3) ◽  
pp. 14-22 ◽  
Author(s):  
Hiroko Nakamura ◽  
Wei-Guang Ding ◽  
Mitsuru Sanada ◽  
Kengo Maeda ◽  
Hiromichi Kawai ◽  
...  
Keyword(s):  
Functional Role ◽  
Delayed Rectifier ◽  
Adult Mice ◽  
K Current ◽  
Left And Right ◽  
Right Atria

Effects of hyperthyroidism on delayed rectifier K+ currents in left and right murine atria

2005 ◽  
Vol 289 (4) ◽  
pp. H1448-H1455 ◽  
Author(s):  
Ying Hu ◽  
S. V. Penelope Jones ◽  
Wolfgang H. Dillmann
Keyword(s):  
Protein Expression ◽  
Left Atrium ◽  
Right Atrial ◽  
Delayed Rectifier ◽  
Rnase Protection ◽  
Expression Levels ◽  
Mrna And Protein Expression ◽  
Left And Right ◽  
The Right ◽  
Right Atria

Hyperthyroidism has been associated with atrial fibrillation (AF); however, hyperthyroidism-induced ion channel changes that may predispose to AF have not been fully elucidated. To understand the electrophysiological changes that occur in left and right atria with hyperthyroidism, the patch-clamp technique was used to compare action potential duration (APD) and whole cell currents in myocytes from left and right atria from both control and hyperthyroid mice. Additionally, RNase protection assays and immunoblotting were performed to evaluate the mRNA and protein expression levels of K+ channel α-subunits in left and right atria. The results showed that 1) in control mice, the APD was shorter and the ultra-rapid delayed rectifier K+ conductance ( IKur) and the sustained delayed rectifier K+ conductance ( Iss) were larger in the left than in the right atrium; also, mRNA and protein expression levels of Kv1.5 and Kv2.1 were higher in the left atrium; 2) in hyperthyroid mice, the APD was shortened and IKur and Iss were increased in both left and right atrial myocytes, and the protein expression levels of Kv1.5 and Kv2.1 were increased significantly in both atria; and 3) the influence of hyperthyroidism on APD and delayed rectifier K+ currents was more prominent in right than in left atrium, which minimized the interatrial APD difference. In conclusion, hyperthyroidism resulted in more significant APD shortening and greater delayed rectifier K+ current increases in the right vs. the left atrium, which can contribute to the propensity for atrial arrhythmia in hyperthyroid heart.

Mechanisms of Sevoflurane-induced Myocardial Preconditioning in Isolated Human Right Atria In Vitro 

2003 ◽  
Vol 99 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Alexandra Yvon ◽  
Jean-Luc Hanouz ◽  
Benoît Haelewyn ◽  
Xavier Terrien ◽  
Massimo Massetti ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
Adenosine Triphosphate ◽  
Human Myocardium ◽  
Right Atrial ◽  
Human Right ◽  
Myocardial Preconditioning ◽  
Right Atria

Background The authors examined the role of adenosine triphosphate-sensitive potassium channels and adenosine A(1) receptors in sevoflurane-induced preconditioning on isolated human myocardium. Methods The authors recorded isometric contraction of human right atrial trabeculae suspended in oxygenated Tyrode's solution (34 degrees C; stimulation frequency, 1 Hz). In all groups, a 30-min hypoxic period was followed by 60 min of reoxygenation. Seven minutes before hypoxia reoxygenation, muscles were exposed to 4 min of hypoxia and 7 min of reoxygenation or 15 min of sevoflurane at concentrations of 1, 2, and 3%. In separate groups, sevoflurane 2% was administered in the presence of 10 microm HMR 1098, a sarcolemmal adenosine triphosphate-sensitive potassium channel antagonist; 800 microm 5-hydroxy-decanoate, a mitochondrial adenosine triphosphate-sensitive potassium channel antagonist; and 100 nm 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A(1) receptor antagonist. Recovery of force at the end of the 60-min reoxygenation period was compared between groups (mean +/- SD). Results Hypoxic preconditioning (90 +/- 4% of baseline) and sevoflurane 1% (82 +/- 3% of baseline), 2% (92 +/- 5% of baseline), and 3% (85 +/- 7% of baseline) enhanced the recovery of force after 60 min of reoxygenation compared with the control groups (52 +/- 9% of baseline). This effect was abolished in the presence of 5-hydroxy-decanoate (55 +/- 14% of baseline) and 8-cyclopentyl-1,3-dipropylxanthine (58 +/- 16% of baseline) but was attenuated in the presence of HMR 1098 (73 +/- 10% of baseline). Conclusions In vitro, sevoflurane preconditions human myocardium against hypoxia through activation of adenosine triphosphate-sensitive potassium channels and stimulation of adenosine A(1) receptors.

scholarly journals Amitriptyline functionally antagonizes cardiac H2 histamine receptors in transgenic mice and human atria

2021 ◽  
Author(s):  
Joachim Neumann ◽  
Maximilian Benedikt Binter ◽  
Charlotte Fehse ◽  
Margaréta Marušáková ◽  
Maren Luise Büxel ◽  
...  
Keyword(s):  
Antidepressant Drug ◽  
Histamine Receptor ◽  
Right Atrial ◽  
Inotropic Effects ◽  
Positive Inotropic Effects ◽  
Contractile Parameters ◽  
Left And Right ◽  
Chronotropic Effects ◽  
Perfused Hearts ◽  
Right Atria

AbstractWe have previously shown that histamine (2-(1H-imidazol-4-yl)ethanamine) exerted concentration-dependent positive inotropic effects (PIE) or positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic (H2R-TG) mice that overexpress the human H2 histamine receptor (H2R) in the heart; however, the effects were not seen in their wild-type (WT) littermates. Amitriptyline, which is still a highly prescribed antidepressant drug, was reported to act as antagonist on H2Rs. Here, we wanted to determine whether the histamine effects in H2R-TG were antagonized by amitriptyline. Contractile studies were performed on isolated left and right atrial preparations, isolated perfused hearts from H2R-TG and WT mice and human atrial preparations. Amitriptyline shifted the concentration-dependent PIE of histamine (1 nM–10 μM) to higher concentrations (rightward shift) in left atrial preparations from H2R-TG. Similarly, in isolated perfused hearts from H2R-TG and WT mice, histamine increased the contractile parameters and the phosphorylation state of phospholamban (PLB) at serine 16 in the H2R-TG mice, but not in the WT mice. However, the increases in contractility and PLB phosphorylation were attenuated by the addition of amitriptyline in perfused hearts from H2R-TG. In isolated electrically stimulated human atria, the PIE of histamine that was applied in increasing concentrations from 1 nM to 10 μM was reduced by 10-μM amitriptyline. In summary, we present functional evidence that amitriptyline also acts as an antagonist of contractility at H2Rs in H2R-TG mouse hearts and in the human heart which might in part explain the side effects of amitriptyline.

Comparison of time- and voltage-dependent K+ currents in myocytes from left and right atria of adult mice

2003 ◽  
Vol 285 (5) ◽  
pp. H1837-H1848 ◽  
Author(s):  
Alan E. Lomax ◽  
Colleen S. Kondo ◽  
Wayne R. Giles
Keyword(s):  
Current Density ◽  
Right Atrium ◽  
Left Atrial ◽  
Right Atrial ◽  
Atrial Myocytes ◽  
Adult Mice ◽  
Voltage Dependent ◽  
Left And Right ◽  
The Right ◽  
Right Atria

Consistent differences in K+ currents in left and right atria of adult mouse hearts have been identified by the application of current- and voltage-clamp protocols to isolated single myocytes. Left atrial myocytes had a significantly ( P < 0.05) larger peak outward K+ current density than myocytes from the right atrium. Detailed analysis revealed that this difference was due to the rapidly activating sustained K+ current, which is inhibited by 100 μM 4-aminopyridine (4-AP); this current was almost three times larger in the left atrium than in the right atrium. Accordingly, 100 μM 4-AP caused a significantly ( P < 0.05) larger increase in action potential duration in left than in right atrial myocytes. Inward rectifier K+ current density was also significantly ( P < 0.05) larger in left atrial myocytes. There was no difference in the voltage-dependent L-type Ca2+ current between left and right atria. As expected from this voltage-clamp data, the duration of action potentials recorded from single myocytes was significantly ( P < 0.05) shorter in myocytes from left atria, and left atrial tissue was found to have a significantly ( P < 0.05) shorter effective refractory period than right atrial tissue. These results reveal similarities between mice and other mammalian species where the left atrium repolarizes more quickly than the right, and provide new insight into cellular electrophysiological mechanisms responsible for this difference. These findings, and previous results, suggest that the atria of adult mice may be a suitable model for detailed studies of atrial electrophysiology and pharmacology under control conditions and in the context of induced atrial rhythm disturbances.

Vasopressin and renin responses to hemorrhage in conscious, cardiac-denervated dogs

1983 ◽  
Vol 245 (3) ◽  
pp. H399-H405 ◽  
Author(s):  
B. C. Wang ◽  
W. D. Sundet ◽  
M. O. Hakumaki ◽  
K. L. Goetz
Keyword(s):  
Dominant Role ◽  
Plasma Renin ◽  
Aortic Pressure ◽  
Conscious Dogs ◽  
Right Atrial ◽  
Pulmonary Arterial ◽  
Left And Right ◽  
Plasma Arginine ◽  
Cardiac Receptors

We measured plasma arginine vasopressin (AVP) and plasma renin activity (PRA) during continuous hemorrhage in cardiac-denervated and sham-operated conscious dogs. Hemorrhage produced comparable decreases in aortic pressure, cardiac output, stroke volume, pulmonary arterial pressure, and left and right atrial pressures in each group of dogs. After 10 ml blood/kg body wt had been removed, AVP was increased in sham-operated dogs (P less than 0.05) but not in cardiac-denervated dogs. After 20 and 30 ml blood/kg body wt had been removed, AVP was increased in all dogs, but the response was markedly attenuated in cardiac-denervated dogs. Hemorrhage at 10 and 20 ml/kg caused comparable increases in PRA in each group of dogs. However, at 30 ml/kg hemorrhage the increase in PRA was significantly higher in cardiac-denervated dogs than in sham-operated dogs. Our results suggest that cardiac receptors play a dominant role in mediating the release of AVP during hemorrhage in conscious dogs. In contrast, we found no evidence for a dominant role of cardiac receptors in mediating renin secretion during hemorrhage.

Vasopressin and ANG II in the control of ACTH secretion and arterial and atrial pressures

1989 ◽  
Vol 256 (2) ◽  
pp. R339-R347 ◽  
Author(s):  
V. L. Brooks
Keyword(s):  
Arterial Pressure ◽  
Right Atrial ◽  
Ang Ii ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Arterial Blood ◽  
Acth Concentration ◽  
Left And Right ◽  
Dose Dependent

Hypotension stimulates the secretion of adrenocorticotropin (ACTH) and vasopressin (AVP) and increases plasma levels of angiotensin II (ANG II). Because AVP and ANG II increase ACTH secretion, the present experiments were performed to evaluate the role of these peptides in the increases in plasma ACTH and glucocorticoid concentrations produced by hypotension in conscious dogs. This was accomplished by determining whether administration of receptor antagonists to vasopressin, [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine]Arg8-vasopressin, and ANG II (saralasin), reduced the ACTH and glucocorticoid responses to infusion of four doses of the vasodilator nitroprusside. Nitroprusside (NP) infusion produced dose-dependent decreases in mean arterial pressure. Larger decreases in arterial pressure were produced in dogs pretreated with the AVP antagonist or with both saralasin and the vasopressin antagonist. Left and right atrial pressures also fell with NP infusion, and larger decreases in atrial pressures were found in dogs pretreated with the AVP antagonist. Finally, NP infusion increased plasma glucocorticoid concentration and plasma ACTH concentration. Both the glucocorticoid and the ACTH responses to hypotension were reduced in dogs given the AVP antagonist and in dogs given both saralasin and the AVP antagonist, but there was no difference in the effect of AVP blockade alone vs. the effect of combined AVP and ANG II blockade. These data suggest that AVP, but not ANG II, is required for normal glucocorticoid and ACTH responses to hypotension. They also suggest that AVP is necessary for normal maintenance of arterial blood pressure and atrial pressures during NP infusion.

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