scholarly journals Enhanced Vasoconstriction Mediated by α1-Adrenergic Mechanisms in Small Femoral Arteries in Newborn Llama and Sheep Gestated at Low and High Altitudes

2021 ◽  
Vol 12 ◽  
Author(s):  
Fernando A. Moraga ◽  
Roberto V. Reyes ◽  
Germán Ebensperger ◽  
Vasthi López ◽  
Aníbal J. Llanos
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Hypobaric Hypoxia ◽  
Chronic Hypoxia ◽  
Maximal Contraction ◽  
Femoral Arteries ◽  
Neonatal Life ◽  
Vasoconstrictor Response ◽  
Low Altitude ◽  
The Impact

The authors previously demonstrated that newborn llama (NBLL) express high levels of α1 adrenergic receptors, which provide a potent vasoconstriction response when compared with newborn sheep (NBSH) gestated at sea level. However, data regarding the impact of chronic gestational hypobaric hypoxia on α-adrenergic vasoconstriction in the neonatal life has not been studied. We evaluated if gestation under chronic hypobaric hypoxia modifies α1-adrenergic vasoconstrictor function in NBLL and NBSH. We compared the vasoconstrictor response induced by potassium and α-adrenergic stimuli in isolated small femoral arteries of NBLL and NBSH gestated at high altitude (HA; 3,600 m) or low altitude (LA; 580 m). The maximal contraction (RMAX) and potency (EC50) to potassium, noradrenaline (NA), and phenylephrine (PHE) were larger in HA-NBLL than LA-NBLL. RMAX to potassium, NA, and PHE were lower in HA-NBSH when compared with LA-NBSH and potency results were similar. Competitive blockade with prazosin showed that RNLL LA/HA have a similar pA2. In contrast, NBSH had increased pA2 values in HA when compared with LA. Finally, small femoral arteries denudated or treated with LNAME in LA and HA lacked NO or endothelium participation in response to PHE stimulation. In contrast, NBSH displayed that denudation or blockade with LNAME support NO or endothelium participation in response to PHE activation. In conclusion, HA chronic hypoxia enhances α1 adrenergic receptor activity in small femoral arteries in NBLL to a higher degree than NBSH, implying a higher vasoconstriction function.

Effects of hypoxia on density of beta-adrenergic receptors

1981 ◽  
Vol 50 (2) ◽  
pp. 363-366 ◽  
Author(s):  
N. F. Voelkel ◽  
L. Hegstrand ◽  
J. T. Reeves ◽  
I. F. McMurty ◽  
P. B. Molinoff
Keyword(s):  
High Altitude ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Low Dose ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Altitude Exposure

Exposure to chronic hypoxia results in a lower resting heart rate and a blunted cardiovascular responsiveness to beta-adrenergic receptor stimulation. Possible effects of acclimatization to high altitude on the binding of [125I]iodohydroxybenzylpindolol to beta-adrenergic receptors on membranes of right and left ventricles of rat heart were determined. Chronic high-altitude exposure led to a decrease in the density of beta-adrenergic receptors in nonhypertrophied left ventricles as well as in hypertrophied right ventricles. The affinity of the receptor for the radioligand was not changed by the exposure to high altitude, suggesting that the properties of the receptor were not affected. Basal and isoproterenol-stimulated adenylate cyclase activities were decreased in membranes prepared from hearts and pulmonary arteries of rats acclimatized to high altitude. The loss of cardiac beta-adrenergic receptors in rats adapted to high altitude was prevented by the chronic coadministration of a low dose of DL-propranolol. The results suggest that changes in beta-adrenergic receptor density may partially explain the hemodynamic adaptation that occurs with chronic hypoxia. These decreases may be due to a loss of functional beta-adrenergic receptors caused by chronically elevated concentrations of circulating neurally released catecholamines.

Abstract 52: Temporal Regulation Of Cardiac Cytokine Expression in Response to Chronic β-Adrenergic Receptor Stimulation

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Laurel A Grisanti ◽  
Ashley A Repas ◽  
Rhonda L Carter ◽  
Jennifer A Talarico ◽  
Jessica L Gold ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cytokine Expression ◽  
Temporal Regulation ◽  
Whole Transcriptome Analysis ◽  
Β Adrenergic Receptors ◽  
The Impact ◽  
Whole Transcriptome

Chronic catecholamine stimulation of β-adrenergic receptors (βAR) is ultimately deleterious during heart failure (HF). While alterations in cytokines contribute to HF pathogenesis and βAR have been demonstrated to regulate cytokines in different models of HF, a comprehensive understanding of this relationship is lacking. Thus, we sought to characterize the impact of chronic βAR signaling on cardiac cytokine expression in vivo. C57BL/6 mice underwent infusion with vehicle or isoproterenol (Iso; 3 mg/kg/day) via minipumps for 1 or 2 weeks and cardiac function was monitored via echocardiography. At study termination, hearts were excised and assessed for changes in hypertrophy, fibrosis and apoptosis, each of which were enhanced by Iso. Expression of cardiac transcripts were assessed via whole transcriptome analysis, where 780 and 689 transcripts were significantly altered at 1 and 2 weeks of Iso, respectively, with only 115 transcripts regulated similarly between the two cohorts. Significant changes in cytokine transcript expression was observed in response to chronic Iso and Ingenuity Pathway Analysis (IPA) predicted the involvement of additional upstream cytokine regulators potentially regulated by Iso. Transcriptome results and IPA predictions were confirmed via qRT-PCR. A cytokine array also confirmed temporally-distinct alterations in the expression of 42 cytokines at the protein level. Differential alterations in cytokine expression resulting from 1 versus 2 weeks of Iso infusion suggest that cytokine-directed therapies may have distinct temporally-dependent consequences on cardiac function and survival under conditions of chronic catecholamine stress.

Depressed myocardial function in the goat at high altitude

1976 ◽  
Vol 41 (3) ◽  
pp. 356-361 ◽  
Author(s):  
C. E. Tucker ◽  
W. E. James ◽  
M. A. Berry ◽  
C. J. Johnstone ◽  
R. F. Grover
Keyword(s):  
High Altitude ◽  
Hypobaric Hypoxia ◽  
Chronic Hypoxia ◽  
Myocardial Function ◽  
Left Ventricular ◽  
Cardiac Performance ◽  
Left Ventricular Cavity ◽  
Wave Form ◽  
Low Altitude ◽  
The Relationship

To determine if depressed myocardial function contributes to the reported decrease in cardiac performance at high altitude, six chronically instrumented, unsedated goats were studied before, during, and after 2-wk exposureto hypobaric hypoxia (PaO2 44 mmHg). Undistorted ventricular pressure wave form was obtained from a miniature transducer implanted in the left ventricular cavity. The relationship between (dP/dt)/28P and P was extrapolated toobtain Vmax as an index of myocardial function. With beta sympathetic blockade (practolol) and pacing to reproduce heart rates, Vmax was uniformly andsignificantly depressed (P less than 0.01) during chronic hypoxia, and returned to control values following descent to low altitude. Likewise, stroke volume following saline infusion was decreased at high altitude and returned to control values following descent. Acute relief of hypoxia at high altitude by administration of 100% oxygen by mask did not reverse the depressedVmax. These findings indicate that chronic hypobaric hypoxia produces a depression of myocardial function which is reversible by chronic but not acuterelief of hypoxia.

Downregulation of hypoxic vasoconstriction by chronic hypoxia in rabbits: effects of nitric oxide

2003 ◽  
Vol 284 (3) ◽  
pp. H931-H938 ◽  
Author(s):  
Norbert Weissmann ◽  
Matthias Nollen ◽  
Boris Gerigk ◽  
Hossein Ardeschir Ghofrani ◽  
Ralph Theo Schermuly ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Vascular Reactivity ◽  
Chronic Hypoxia ◽  
Heart Hypertrophy ◽  
Right Heart ◽  
Vasoconstrictor Response ◽  
Alveolar Hypoxia ◽  
The Impact

Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion to ventilation for optimizing pulmonary gas exchange. Chronic alveolar hypoxia results in vascular remodeling and pulmonary hypertension. Previous studies have reported conflicting results of the effect of chronic alveolar hypoxia on pulmonary vasoreactivity and the contribution of nitric oxide (NO), which may be related to species and strain differences as well as to the duration of chronic hypoxia. Therefore, we investigated the impact of chronic hypoxia on HPV in rabbits, with a focus on lung NO synthesis. After exposure of the animals to normobaric hypoxia (10% O2) for 1 day to 10 wk, vascular reactivity was investigated in ex vivo perfused normoxic ventilated lungs. Chronic hypoxia induced right heart hypertrophy and increased normoxic vascular tone within weeks. The vasoconstrictor response to an acute hypoxic challenge was strongly downregulated within 5 days, whereas the vasoconstrictor response to the thromboxane mimetic U-46619 was maintained. The rapid downregulation of HPV was apparently not linked to changes in the lung vascular NO system, detectable in the exhaled gas and by pharmacological blockage of NO synthesis. Treatment of the animals with long-term inhaled NO reduced right heart hypertrophy and partially maintained the reactivity to acute hypoxia, without any impact on the endogenous NO system being noted. We conclude that chronic hypoxia causes rapid downregulation of acute HPV as a specific event, preceding the development of major pulmonary hypertension and being independent of the lung vascular NO system. Long-term NO inhalation partially maintains the strength of the hypoxic vasoconstrictor response.

Effects of long-term high-altitude hypoxemia on alpha 1-adrenergic receptors in the ovine uterine artery

1996 ◽  
Vol 270 (3) ◽  
pp. H1001-H1007 ◽  
Author(s):  
X. Q. Hu ◽  
L. D. Longo ◽  
R. D. Gilbert ◽  
L. Zhang
Keyword(s):  
High Altitude ◽  
Sea Level ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Uterine Artery ◽  
Chronic Hypoxia ◽  
Radioligand Binding ◽  
Maximal Response ◽  
Binding Studies ◽  
Uterine Arteries

To elucidate the effects of chronic hypoxia on alpha 1-adrenergic receptor-mediated contractions of the uterine artery, we examined norepinephrine-induced contractions in tissues obtained from near-term (approximately 140 days gestation) pregnant ewes maintained near sea level (approximately 300 m) and at high altitude (3,820 m) from 30 days gestation. Compared with the sea-level controls, contractions induced by norepinephrine in main and fourth-branch uterine arteries of the high-altitude animals were significantly depressed. The norepinephrine dose-response curves were shifted to the right and the concentrations at which 50% of the maximal response was attained were increased 3.2- and 5.7-fold in the main and fourth-branch uterine arteries, respectively. The maximal responses were decreased 22 and 36% in main and fourth-branch uterine arteries, respectively. The dissociation constants of norepinephrine were increased from 0.77 to 1.53 microM and from 0.72 to 2.05 microM in main and fourth-branch uterine arteries, respectively. Radioligand binding studies with [3H]prazosin revealed a decrease in the density of alpha 1-adrenergic receptors in both vessels from high-altitude animals. We conclude that chronic hypoxia depresses alpha 1-adrenergic receptor-induced contractions of conduit- and resistance-type uterine arteries. The depressed contractility is mediated, at least in part, by decreases in alpha 1-adrenergic receptor density and agonist binding affinity.

Inhibition of Glutamatergic Synaptic Input to Spinal Lamina IIo Neurons by Presynaptic α2-Adrenergic Receptors

2002 ◽  
Vol 87 (4) ◽  
pp. 1938-1947 ◽  
Author(s):  
Yu-Zhen Pan ◽  
De-Pei Li ◽  
Hui-Lin Pan
Keyword(s):  
Receptor Antagonist ◽  
Synaptic Input ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Dorsal Root ◽  
Primary Afferents ◽  
Noradrenergic System ◽  
Analgesic Action ◽  
Adrenergic Agonists ◽  
Excitatory Synaptic Input

Activation of spinal α2-adrenergic receptors by the descending noradrenergic system and α2-adrenergic agonists produces analgesia. However, the sites and mechanisms of the analgesic action of spinally administered α2-adrenergic receptor agonists such as clonidine are not fully known. The dorsal horn neurons in the outer zone of lamina II (lamina IIo) are important for processing nociceptive information from C-fiber primary afferents. In the present study, we tested a hypothesis that activation of presynaptic α2-adrenergic receptors by clonidine inhibits the excitatory synaptic input to lamina IIo neurons. Whole cell voltage-clamp recordings were performed on visualized lamina IIo neurons in the spinal cord slice of rats. The miniature excitatory postsynaptic currents (mEPSCs) were recorded in the presence of tetrodotoxin, bicuculline, and strychnine. The evoked EPSCs were obtained by electrical stimulation of the dorsal root entry zone or the attached dorsal root. Both mEPSCs and evoked EPSCs were abolished by application of 6-cyano-7-nitroquinoxaline-2,3-dione. Clonidine (10 μM) significantly decreased the frequency of mEPSCs from 5.8 ± 0.9 to 2.7 ± 0.6 Hz (means ± SE) without altering the amplitude and the decay time constant of mEPSCs in 25 of 27 lamina IIo neurons. Yohimbine (2 μM, an α2-adrenergic receptor antagonist), but not prazosin (2 μM, an α1-adrenergic receptor antagonist), blocked the inhibitory effect of clonidine on the mEPSCs. Clonidine (1–20 μM, n = 8) also significantly attenuated the peak amplitude of evoked EPSCs in a concentration-dependent manner. The effect of clonidine on evoked EPSCs was abolished in the presence of yohimbine ( n = 5). These data suggest that clonidine inhibits the excitatory synaptic input to lamina IIo neurons through activation of α2-adrenergic receptors located on the glutamatergic afferent terminals. Presynaptic inhibition of glutamate release from primary afferents onto lamina IIoneurons likely plays an important role in the analgesic action produced by activation of the descending noradrenergic system and α2-adrenergic agonists.

scholarly journals Role of beta-adrenergic receptor subtypes in pig uterus contractility with inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Barbara Jana ◽  
Jarosław Całka
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Domestic Animals ◽  
Inhibitory Effect ◽  
Receptor Subtypes ◽  
Beta Adrenergic Receptor ◽  
Pharmacological Modulation ◽  
Uterine Inflammation ◽  
Myometrial Contractility

AbstractUterine inflammation is a very common and serious condition in domestic animals. To development and progression of this pathology often lead disturbances in myometrial contractility. Participation of β1-, β2- and β3-adrenergic receptors (ARs) in noradrenaline (NA)-influenced contractility of the pig inflamed uterus was studied. The gilts of SAL- and E.coli-treated groups were administered saline or E.coli suspension into the uterine horns, respectively. Laparotomy was only done in the CON group. Compared to the period before NA administration, this neurotransmitter reduced the tension, amplitude and frequency in uterine strips of the CON and SAL groups. In the E.coli group, NA decreased the amplitude and frequency, and these parameters were lower than in other groups. In the CON, SAL and E.coli groups, β1- and β3-ARs antagonists in more cases did not significantly change and partly eliminated NA inhibitory effect on amplitude and frequency, as compared to NA action alone. In turn, β2-ARs antagonist completely abolished NA relaxatory effect on these parameters in three groups. Summarizing, NA decreases the contractile amplitude and frequency of pig inflamed uterus via all β-ARs subtypes, however, β2-ARs have the greatest importance. Given this, pharmacological modulation of particular β-ARs subtypes can be used to increase inflamed uterus contractility.

scholarly journals Overexpression of beta-arrestin and beta-adrenergic receptor kinase augment desensitization of beta 2-adrenergic receptors.

1993 ◽  
Vol 268 (5) ◽  
pp. 3201-3208
Author(s):  
S. Pippig ◽  
S. Andexinger ◽  
K. Daniel ◽  
M. Puzicha ◽  
M.G. Caron ◽  
...  
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Receptor Kinase ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Beta 2

scholarly journals Impact of Aldosterone on the Failing Myocardium: Insights from Mitochondria and Adrenergic Receptors Signaling and Function

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1552
Author(s):  
Mariona Guitart-Mampel ◽  
Pedro Urquiza ◽  
Jordana I. Borges ◽  
Anastasios Lymperopoulos ◽  
Maria E. Solesio
Keyword(s):  
Mitochondrial Dysfunction ◽  
G Protein ◽  
Adrenergic Receptor ◽  
Cellular Level ◽  
Cardiac Physiology ◽  
Failing Heart ◽  
Receptor Kinases ◽  
And Function ◽  
The Impact ◽  
G Protein Coupled

The mineralocorticoid aldosterone regulates electrolyte and blood volume homeostasis, but it also adversely modulates the structure and function of the chronically failing heart, through its elevated production in chronic human post-myocardial infarction (MI) heart failure (HF). By activating the mineralocorticoid receptor (MR), a ligand-regulated transcription factor, aldosterone promotes inflammation and fibrosis of the heart, while increasing oxidative stress, ultimately induding mitochondrial dysfunction in the failing myocardium. To reduce morbidity and mortality in advanced stage HF, MR antagonist drugs, such as spironolactone and eplerenone, are used. In addition to the MR, aldosterone can bind and stimulate other receptors, such as the plasma membrane-residing G protein-coupled estrogen receptor (GPER), further complicating it signaling properties in the myocardium. Given the salient role that adrenergic receptor (ARs)—particularly βARs—play in cardiac physiology and pathology, unsurprisingly, that part of the impact of aldosterone on the failing heart is mediated by its effects on the signaling and function of these receptors. Aldosterone can significantly precipitate the well-documented derangement of cardiac AR signaling and impairment of AR function, critically underlying chronic human HF. One of the main consequences of HF in mammalian models at the cellular level is the presence of mitochondrial dysfunction. As such, preventing mitochondrial dysfunction could be a valid pharmacological target in this condition. This review summarizes the current experimental evidence for this aldosterone/AR crosstalk in both the healthy and failing heart, and the impact of mitochondrial dysfunction in HF. Recent findings from signaling studies focusing on MR and AR crosstalk via non-conventional signaling of molecules that normally terminate the signaling of ARs in the heart, i.e., the G protein-coupled receptor-kinases (GRKs), are also highlighted.

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