Heightened α1A-adrenergic receptor activity suppresses ischaemia/reperfusion-induced Ins(1,4,5)P3 generation in the mouse heart: a comparison with ischaemic preconditioning

2007 ◽  
Vol 114 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Fatemeh Amirahmadi ◽  
Lynne Turnbull ◽  
Xiao-Jun Du ◽  
Robert M. Graham ◽  
Elizabeth A. Woodcock
Keyword(s):  
Transgenic Mice ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Mouse Heart ◽  
Ischaemic Preconditioning ◽  
Receptor Signalling ◽  
Ischaemia Reperfusion ◽  
Ischaemia And Reperfusion ◽  
Ischaemic Insult ◽  
Stimulation Of

Reperfusion of ischaemic rat or mouse hearts causes NE [noradrenaline (‘norepinephrine’)] release, stimulation of α1-ARs (α1-adrenergic receptors), PLC (phospholipase C) activation, Ins(1,4,5)P3 generation and the development of arrhythmias. In the present study, we examined the effect of increased α1A-AR drive on these responses. In hearts from non-transgenic mice (α1A-WT), Ins(1,4,5)P3 generation was observed after 2 min of reperfusion following 30 min of zero-flow ischaemia. No Ins(1,4,5)P3 response was observed in hearts from transgenic mice with 66-fold overexpression of α1A-AR (α1A-TG). This was despite the fact that α1A-TG hearts had 8–10-fold higher PLC responses to NE than α1A-WT under normoxic conditions. The immediate phospholipid precursor of Ins(1,4,5)P3, PtdIns(4,5)P2, responded to ischaemia and reperfusion similarly in α1A-WT and α1A-TG mice. Thus the lack of Ins(1,4,5)P3 generation in α1A-TG mice is not caused by limited availability of PtdIns(4,5)P2. Overall, α1-AR-mediated PLC activity was markedly enhanced in α1A-WT mice under reperfusion conditions, but responses in α1A-TG mice were not significantly different in normoxia and post-ischaemic reperfusion. Ischaemic preconditioning prevented Ins(1,4,5)P3 generation after 30 min of ischaemic insult in α1A-WT mice. However, the precursor lipid PtdIns(4,5)P2 was also reduced by preconditioning, whereas heightened α1A-AR activity did not influence PtdIns(4,5)P2 responses in reperfusion. Thus preconditioning and α1A-AR overexpression have different effects on early signalling responses, even though both prevented Ins(1,4,5)P3 generation. These studies demonstrate a selective inhibitory action of heightened α1A-AR activity on immediate post-receptor signalling responses in early post-ischaemic reperfusion.

Response to cardiac sympathetic activation in transgenic mice overexpressing beta 2-adrenergic receptor

1996 ◽  
Vol 271 (2) ◽  
pp. H630-H636 ◽  
Author(s):  
X. J. Du ◽  
E. Vincan ◽  
D. M. Woodcock ◽  
C. A. Milano ◽  
A. M. Dart ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Nerve Stimulation ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Adrenergic Stimulation ◽  
Adrenergic Activity ◽  
Beta 2 ◽  
Stimulation Of

Transgenic mice have been created with 200-fold overexpression of beta 2-adrenergic receptors specifically in the heart. Cardiac function was studied in these transgenic mice and their controls at baseline and during isoproterenol perfusion or sympathetic nerve stimulation. The model used was an in situ buffer-perfused, innervated heart, and the left ventricle maximal derivative of pressure over time (dP/dtmax) and heart rate (HR) were measured. Basal HR and dP/dtmax were 30-40% higher in hearts from transgenic mice than controls. Electrical stimulation of sympathetic nerves (2, 4, and 8 Hz) or infusion of isoproterenol markedly increased HR and dP/dtmax in control hearts. Hearts from transgenic mice did not respond to isoproterenol. However, hearts from transgenic mice retained the HR response to nerve stimulation, and a small increase in dP/dtmax was also detected. Atenolol inhibited the response to nerve stimulation in control hearts but not that in hearts from transgenic mice. ICI-118551 inhibited the response in transgenic hearts. Basal HR and dP/dtmax were decreased by ICI-118551 only in transgenic hearts. Thus overexpression of cardiac beta 2-receptors modifies beta-adrenergic activity, but the responses to endogenous and exogenous adrenergic stimulation are affected differently.

α-Adrenergic receptor modulation of the intrathoracic efferent sympathetic nervous system regulating the canine heart

1989 ◽  
Vol 67 (10) ◽  
pp. 1199-1204 ◽  
Author(s):  
J. A. Armour
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Blocking Agent ◽  
Sympathetic Ganglia ◽  
Canine Heart ◽  
Receptor Modulation ◽  
Adrenergic Antagonist ◽  
Cervical Ganglia ◽  
Β Adrenergic Receptors ◽  
Stimulation Of

The augmentation of ventricular inotropism induced by electrical stimulation of acutely decentralized efferent sympathetic preganglionic axons was reduced, but still present, following administraiton of hexamethonium (10 mg/kg i.v.). While hexamethonium continued to be administered, the cardiac augmentations so induced were enhanced significantly following administration of the α-adrenergic receptor blocking agent, phentolamine myselate (1 mg/kg i.v.). Stimulation of the sympathetic efferent postganglionic axons in cardiopulmonary nerves induced cardiac augmentations that were unchanged following administration of these agents singly or together. The cardiac augmentations induced by stimulation of efferent preganglionic sympathetic axons were unchanged when phentolamine was administered alone. The augmentations of cardiac inotropism induced by efferent postganglionic sympathetic axonal stimulation were decreased following local administration of the β-adrenergic antagonist timolol into the ipsilateral stellate and middle cervical ganglia. Thereafter, these augmentations were unchanged following the subsequent intravenous administration of phentolamine. It is concluded that the activation of cardiac neurons in the stellate and middle cervical ganglia by stimulation of efferent preganglionic sympathetic axons can be modified by α-adrenergic receptors and that these effects are dependent upon β-adrenergic receptors, not nicotinic ones, in intrathoracic ganglia.Key words: α-adrenergic inotropism, sympathetic ganglia, hexamethonium, phentolamine.

Modulation of beta-adrenergic receptor-stimulated lipolysis in the heart by prostaglandins

1996 ◽  
Vol 271 (3) ◽  
pp. E556-E562
Author(s):  
Y. Ruan ◽  
H. Kan ◽  
C. Cano ◽  
K. U. Malik
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Rabbit Heart ◽  
Receptor Activation ◽  
Prostaglandin Synthesis ◽  
Prostaglandin I2 ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Endogenous Prostaglandin ◽  
Stimulation Of

The purpose of the present study was to investigate the contribution of prostaglandins to lipolysis elicited by beta-adrenergic receptor activation in the heart. We have studied the effect of prostaglandin E2 (PGE2), prostaglandin I2 (PGI2), and their precursor arachidonic acid (AA) in the presence and absence of a cyclooxygenase inhibitor, sodium meclofenamate, on glycerol output elicited by stimulation of beta-adrenergic receptors in the isolated rabbit heart with isoproterenol (ISOP). Bolus injections of ISOP (475 pmol) produced a constant increase in glycerol and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) output. Infusion of sodium meclofenamate (16 microM) reduced basal and attenuated ISOP-induced 6-keto-PGF1 alpha output and enhanced glycerol output. During inhibition of endogenous prostaglandin synthesis with meclofenamate, infusion of PGI2 or PGE2 (0.1-1 microM) inhibited ISOP-induced glycerol output. Infusion of AA (0.1-1 microM) increased 6-keto-PGF1 alpha and reduced glycerol output. Infusion of sodium meclofenamate abolished the effect of AA to increase 6-keto-PGF1 alpha and to decrease glycerol output. These data suggest that prostaglandins synthesized in the heart act as an inhibitory modulator of beta-adrenergic receptor-stimulated cardiac lipolysis.

Cardiovascular effects of dobutamine during exercise in dogs

1989 ◽  
Vol 257 (3) ◽  
pp. H954-H960
Author(s):  
G. C. Haidet ◽  
T. I. Musch ◽  
D. B. Friedman ◽  
G. A. Ordway
Keyword(s):  
Skeletal Muscle ◽  
Heart Rate ◽  
Blood Flow ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Maximal Exercise ◽  
Cardiovascular Effects ◽  
Receptor Reserve ◽  
Concomitant Reduction ◽  
Stimulation Of

To test the hypothesis that stimulation of adrenergic receptors in the heart is maximal during maximal exercise, and to determine whether generalized stimulation of adrenergic receptors during strenuous exercise produces significant alterations in the normal regional distribution of blood flow that occurs during exercise, we evaluated the cardiovascular effects of the infusion of dobutamine (40 micrograms.kg-1.min-1) in mongrel dogs during treadmill running. During maximal exercise, the dobutamine infusion resulted in a significant (P less than 0.05) increase in heart rate. Exercise capacity, total body O2 consumption (VO2), and maximal arteriovenous O2 difference, however, each were reduced during the infusion of this drug. A concomitant reduction in maximal blood flow to locomotive skeletal muscle occurred. The infusion of dobutamine also resulted in an increase in heart rate at a strenuous level of submaximal exercise. However, unlike during maximal exercise, VO2 was unchanged. Blood flow to locomotive skeletal muscle increased, and there was a concomitant reduction in arteriovenous O2 difference. Blood flow reductions that normally occur in splanchnic circulations during strenuous and during maximal exercise were generally somewhat attenuated during the infusion of this drug. Thus, dobutamine, a sympathomimetic agent, produces significant cardiovascular effects when infused in high doses during exercise. Our results demonstrate that beta-adrenergic receptor reserve exists in the heart during maximal exercise in dogs. In addition, the peripheral responses that occur during the infusion of the drug provide additional evidence that different degrees of adrenergic receptor reserve normally appear to be present within different regional circulations during strenuous and during maximal exercise.

scholarly journals Noradrenergic control of central oxytocin release during lactation in rats

1998 ◽  
Vol 274 (3) ◽  
pp. E453-E458 ◽  
Author(s):  
Steven L. Bealer ◽  
William R. Crowley
Keyword(s):  
Cerebrospinal Fluid ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Additional Experiment ◽  
Adrenergic Agonist ◽  
Magnocellular Nuclei ◽  
Artificial Cerebrospinal Fluid ◽  
Oxytocin Release ◽  
Stimulation Of

Noradrenergic systems regulate the systemic release of oxytocin (OT) in lactating rats. However, a role for norepinephrine (NE) in release of OT within the magnocellular nuclei during suckling has not been established. These studies were designed to determine 1) if suckling induces NE release in the supraoptic (SON) and paraventricular (PVN) nuclei of conscious rats and 2) the role of NE in the central, intranuclear release of OT within these nuclei. Female Holtzman rats were implanted with microdialysis probes adjacent to the PVN or SON on lactation days 8- 12. The following day, the pups were isolated from the dams for 4 h. Microdialysis probes were perfused with artificial cerebrospinal fluid (ACSF) or with ACSF containing an α- or a β-adrenergic receptor antagonist. Dialysate was collected before, during, and after suckling and analyzed for NE or OT. In an additional experiment, an α- or β-adrenergic agonist was administered via the microdialysis probes into the PVN in nonsuckled, lactating rats. Extracellular NE increased in the PVN during suckling but was not detectable in the SON. OT concentrations in dialysates from the PVN and SON significantly increased during suckling. Blockade of either α- (in both PVN and SON) or β- (PVN) adrenergic receptors prevented the suckling-induced increase in central OT release. OT release was increased in nonsuckled, lactating rats by central application of either an α- or β-adrenergic agonist. These data demonstrate that intranuclear NE release is increased in the PVN by suckling and that subsequent stimulation of both α- and β-noradrenergic receptors mediates intranuclear OT release.

scholarly journals Transgenic Mice Carrying the Human β2-Adrenergic Receptor Gene with its Own Promoter Overexpress β2-Adrenergic Receptors in Liver

1996 ◽  
Vol 241 (2) ◽  
pp. 417-424 ◽  
Author(s):  
Claudine Andre ◽  
Loubna Erraji ◽  
Jesintha Gaston ◽  
Gisele Grimber ◽  
Pascale Briand ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Receptor Gene ◽  
Β2 Adrenergic Receptor ◽  
Adrenergic Receptor Gene

scholarly journals Adrenergic receptor activation involves ATP release and feedback through purinergic receptors

2010 ◽  
Vol 299 (5) ◽  
pp. C1118-C1126 ◽  
Author(s):  
Yuka Sumi ◽  
Tobias Woehrle ◽  
Yu Chen ◽  
Yongli Yao ◽  
Andrew Li ◽  
...  
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Purinergic Receptors ◽  
Atp Release ◽  
Feedback Mechanisms ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
293 Cells ◽  
Formyl Peptide ◽  
Stimulation Of

Formyl peptide receptor-induced chemotaxis of neutrophils depends on the release of ATP and autocrine feedback through purinergic receptors. Here, we show that adrenergic receptor signaling requires similar purinergic feedback mechanisms. Real-time RT-PCR analysis revealed that human embryonic kidney (HEK)-293 cells express several subtypes of adrenergic (α1-, α2-, and β-receptors), adenosine (P1), and nucleotide receptors (P2). Stimulation of Gq-coupled α1-receptors caused release of cellular ATP and MAPK activation, which was blocked by inhibiting P2 receptors with suramin. Stimulation of Gi-coupled α2-receptors induced weak ATP release, while Gs-coupled β-receptors caused accumulation of extracellular ADP and adenosine. β-Receptors triggered intracellular cAMP signaling, which was blocked by scavenging extracellular adenosine with adenosine deaminase or by inhibiting A2a adenosine receptors with SCH58261. These findings suggest that adrenergic receptors require purinergic receptors to elicit downstream signaling responses in HEK-293 cells. We evaluated the physiological relevance of these findings using mouse aorta tissue rings. Stimulation of α1-receptors induced ATP release and tissue contraction, which was reduced by removing extracellular ATP with apyrase or in the absence of P2Y2 receptors in aorta rings from P2Y2 receptor knockout mice. We conclude that, like formyl peptide receptors, adrenergic receptors require purinergic feedback mechanisms to control complex physiological processes such as smooth muscle contraction and regulation of vascular tone.

scholarly journals β3-Adrenergic receptor antagonist improves exercise performance in pacing-induced heart failure

2013 ◽  
Vol 305 (6) ◽  
pp. H923-H930 ◽  
Author(s):  
Satoshi Masutani ◽  
Heng-Jie Cheng ◽  
Atsushi Morimoto ◽  
Hiroshi Hasegawa ◽  
Qing-Hua Han ◽  
...  
Keyword(s):  
Heart Failure ◽  
Receptor Antagonist ◽  
Exercise Performance ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Systolic Pressure ◽  
Mechanical Efficiency ◽  
Left Ventricular ◽  
Diastolic Filling ◽  
Stimulation Of

In heart failure (HF), the impaired left ventricular (LV) arterial coupling and diastolic dysfunction present at rest are exacerbated during exercise. We have previously shown that in HF at rest stimulation of β3-adrenergic receptors by endogenous catecholamine depresses LV contraction and relaxation. β3-Adrenergic receptors are activated at higher concentrations of catecholamine. Thus exercise may cause increased stimulation of cardiac β3-adrenergic receptors and contribute to this abnormal response. We assessed the effect of L-748,337 (50 μg/kg iv), a selective β3-adrenergic receptor antagonist (β3-ANT), on LV dynamics during exercise in 12 chronically instrumented dogs with pacing-induced HF. Compared with HF at rest, exercise increased LV end-systolic pressure (PES), minimum LV pressure (LVPmin), and the time constant of LV relaxation (τ) with an upward shift of early diastolic portion of LV pressure-volume loop. LV contractility decreased and arterial elastance (EA) increased. LV arterial coupling (EES/EA) (0.40 vs. 0.51) was impaired. Compared with exercise in HF preparation, exercise after β3-ANT caused similar increases in heart rate and PES but significantly decreased τ (34.9 vs. 38.3 ms) and LVPmin with a downward shift of the early diastolic portion of LV pressure-volume loop and further augmented dV/d tmax. Both EES and EES/EA (0.68 vs. 0.40) were increased. LV mechanical efficiency improved from 0.39 to 0.53. In conclusion, after HF, β3-ANT improves LV diastolic filling; increases LV contractility, LV arterial coupling, and mechanical efficiency; and improves exercise performance.

α1c- and β2-adrenergic receptor mRNA distribution in the bovine mammary gland detected by competitive RT-PCR

2001 ◽  
Vol 68 (4) ◽  
pp. 699-703 ◽  
Author(s):  
OLGA WELLNITZ ◽  
ANDREAS ZURBRIGGEN ◽  
ROBERT R. FRIIS ◽  
JÜRG W. BLUM ◽  
RUPERT M. BRUCKMAIER
Keyword(s):  
Mammary Gland ◽  
Dairy Cows ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Molecular Techniques ◽  
Milk Ejection ◽  
Milk Flow ◽  
Β Adrenergic Receptors ◽  
Stimulation Of ◽  
Receptor Distribution

Milk ejection and milk removal is considerably influenced by the sympathetic nervous system. Stimulation of α-adrenergic receptors by administration of α-adrenergic agonists inhibits alveolar milk ejection and milk removal in dairy cows due to smooth muscle contraction (Blum et al. 1989; Bruckmaier et al. 1991). However, contraction of the teat in response to α-adrenergic receptor stimulation has no influence on milk flow as long as milk is available in the cistern (Bruckmaier et al. 1997). Therefore, α-adrenergic stimulation causes inhibition of transport of alveolar milk into the cistern. On the contrary, the stimulation of β-adrenergic receptors facilitates milk ejection and milk removal in dairy cows (Bernabé & Peeters, 1980; Bruckmaier et al. 1991) because of muscle relaxation. Therefore, the distribution of α- and β-adrenergic receptors plays an important role in the milkability of dairy cows. However, from these in vivo studies it is not possible to distinguish between the different α1- and α2- and β2-receptor subtypes owing to the non-specific nature of the pharmacological agents used.To date, the precise tissue distribution of these different subtypes, in bovine mammary tissue, is unknown. Using molecular techniques, we were interested in the expression of genes that encode α1c and β2 as a preliminary study towards the understanding of noradrenergic receptor-gene expression and regulation in this important system.In addition, α1c- and β2-adrenergic receptors were determined in front and rear quarters of the mammary gland to investigate differences in receptor distribution within the udder and possible relations between adrenergic receptor distribution and the higher milk flow rates in rear than in front quarters (Rothenanger et al. 1995).

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