Maintenance of gasping and restoration of eupnea after hypoxia is impaired following blockers of α1-adrenergic receptors and serotonin 5-HT2 receptors

2008 ◽  
Vol 104 (3) ◽  
pp. 665-673 ◽  
Author(s):  
Walter M. St.-John ◽  
J. C. Leiter
Keyword(s):  
Sodium Channels ◽  
Adrenergic Receptors ◽  
Respiratory Activity ◽  
Rhythmic Activity ◽  
Severe Hypoxia ◽  
Wb 4101 ◽  
Medullary Neurons

In severe hypoxia or ischemia, normal eupneic breathing fails and is replaced by gasping. Gasping serves as part of a process of autoresuscitation by which eupnea is reestablished. Medullary neurons, having a burster, pacemaker discharge, underlie gasping. Conductance through persistent sodium channels is essential for the burster discharge. This conductance is modulated by norepinephrine, acting on α1-adrenergic receptors, and serotonin, acting on 5-HT2 receptors. We hypothesized that blockers of 5-HT2 receptors and α1-adrenergic receptors would alter autoresuscitation. The in situ perfused preparation of the juvenile rat was used. Integrated phrenic discharge was switched from an incrementing pattern, akin to eupnea, to the decrementing pattern comparable to gasping in hypoxic hypercapnia. With a restoration of hyperoxic normocapnia, rhythmic, incrementing phrenic discharge returned within 10 s in most preparations. Following addition of blockers of α1-adrenergic receptors (WB-4101, 0.0625–0.500 μM) and/or blockers of 5-HT2 (ketanserin, 1.25–10 μM) or multiple 5-HT receptors (methysergide, 3.0–10 μM) to the perfusate, incrementing phrenic discharge continued. Fictive gasping was still induced, although it ceased after significantly fewer decrementing bursts than in preparations than received no blockers. Moreover, the time for recovery of rhythmic activity was significantly prolonged. This prolongation was in excess of 100 s in all preparations that received both WB-4101 (above 0.125 μM) and methysergide (above 2.5 μM). We conclude that activation of adrenergic and 5-HT2 receptors is important to sustain gasping and to restore rhythmic respiratory activity after hypoxia-induced depression.

Effects of antihypertensive clonidine congeners on alpha-adrenergic receptors

1982 ◽  
Vol 60 (3) ◽  
pp. 342-344 ◽  
Author(s):  
Milt Titeler ◽  
Philip Seeman
Keyword(s):  
Frontal Cortex ◽  
Strong Correlation ◽  
Adrenergic Receptors ◽  
Alpha Adrenergic Receptors ◽  
Antihypertensive Action ◽  
Wb 4101

Evidence in the literature suggests that the antihypertensive effects of clonidine stem from its action on alpha-2 adrenergic receptors. In order to examine this possibility we tested the effects of 13 congeners of clonidine on the binding of [3H]WB-4101 and [3H]clonidine to calf frontal cortex homogenates; [3H]WB-4101 served as a label for alpha-1 receptors while [3H]clonidine served to label alpha-2 adrenergic receptors. All the substituted imidazolines were two to three orders more potent in inhibiting the binding of [3H]clonidine than they were against [3H]WB-4101. There was a strong correlation between the antihypertensive doses of these congeners and their concentrations required to inhibit the binding of [3H]clonidine. The results are compatible with the concept that the antihypertensive action of clonidine is more likely due to interactions with alpha-2 adrenergic receptors than with alpha-1 receptors.

α-Adrenergic receptors regulate human lymphocyte amiloride-sensitive sodium channels

1998 ◽  
Vol 275 (3) ◽  
pp. C702-C710 ◽  
Author(s):  
James K. Bubien ◽  
Trudy Cornwell ◽  
Anne Lynn Bradford ◽  
Catherine M. Fuller ◽  
Michael D. DuVall ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Sodium Channels ◽  
Adrenergic Receptors ◽  
Binding Proteins ◽  
Second Messengers ◽  
Specific Inhibitor ◽  
Direct Interaction ◽  
Membrane Receptors ◽  
Gtp Binding Proteins ◽  
Gtp Binding

Two independent signal transduction pathways regulate lymphocyte amiloride-sensitive sodium channels (ASSCs), one utilizing cAMP as a second messenger and the other utilizing a GTP-binding protein. This implies that two plasma membrane receptors play a role in the regulation of lymphocyte ASSCs. In this study, we tested the hypothesis that α1- and α2-adrenergic receptors independently regulate lymphocyte ASSCs via the two previously identified second messengers. Direct measurements indicated that norepinephrine increased lymphocyte cAMP and activated ASSCs. The α2-specific inhibitor, yohimbine, blocked this activation, thereby linking α2-adrenergic receptors to ASSC regulation via cAMP. The α1-specific ligand, terazosin, acted as an agonist and activated lymphocyte ASSCs but inhibited ASSC current that had been preactivated by norepinephrine or 8-(4-chlorophenylthio) (CPT)-cAMP. Terazosin had no effect on the lymphocyte whole cell ASSC currents preactivated by treatment with pertussis toxin. This finding indirectly links α1-adrenergic receptors to lymphocyte ASSC regulation via GTP-binding proteins. Terazosin had no direct inhibitory or stimulatory effects on α,β,γ-endothelial sodium channels reconstituted into planar lipid bilayers and expressed in Xenopus oocytes, ruling out a direct interaction between terazosin and the channels. These findings support the hypothesis that both α1- and α2-adrenergic receptors independently regulate lymphocyte ASSCs via GTP-binding proteins and cAMP, respectively.

Muscle shortening increases sensitivity of fatigue to severe hypoxia in canine diaphragm

1991 ◽  
Vol 71 (6) ◽  
pp. 2309-2316 ◽  
Author(s):  
B. T. Ameredes ◽  
M. W. Julian ◽  
T. L. Clanton
Keyword(s):  
Flow Characteristics ◽  
Muscle Length ◽  
Isometric Tension ◽  
Severe Hypoxia ◽  
Mean Power ◽  
Tension Development ◽  
Moderate Hypoxia ◽  
O2 Supply ◽  
Mean Power Output

The effects of inspired O2 on diaphragm tension development during fatigue were assessed using isovelocity (n = 6) and isometric (n = 6) muscle contractions performed during a series of exposures to moderate hypoxia [fraction of inspired O2 (FIO2) = 0.13], hyperoxia (FIO2 = 1), and severe hypoxia (FIO2 = 0.09). Muscle strips were created in situ from the canine diaphragm, attached to a linear ergometer, and electrically stimulated (30 Hz) to contract (contraction = 1.5 s/relaxation = 2 s) from optimal muscle length (Lo = 8.9 cm). Isovelocity contractions shortened to 0.70 Lo, resulting in a mean power output of 210 mW/cm2. Fatigue trials of 35 min duration were performed while inspired O2 was sequentially changed between the experimental mixtures and normoxia (FIO2 = 0.21) for 5-min periods. In this series, severe hypoxia consistently decreased isovelocity tension development by an average of 0.1 kg/cm2 (P less than 0.05), which was followed by a recovery of tension (P less than 0.05) on return to normoxia. These responses were not consistently observed in isometric trials. Neither isovelocity nor isometric tension development was influenced by moderate hypoxia or hyperoxia. These results demonstrate that the in situ diaphragm is relatively insensitive to rapid changes in O2 supply over a broad range and that the tension development of the shortening diaphragm appears to be more susceptible to severe hypoxia during fatigue. This may reflect a difference in either the metabolic or blood flow characteristics of shortening contractions of the diaphragm.

Metabolic state of the in situ perfused trout heart during severe hypoxia

1992 ◽  
Vol 263 (4) ◽  
pp. R798-R804 ◽  
Author(s):  
P. G. Arthur ◽  
J. E. Keen ◽  
P. W. Hochachka ◽  
A. P. Farrell
Keyword(s):  
Creatine Phosphate ◽  
Severe Hypoxia ◽  
Perfused Heart ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Cause Of Failure ◽  
Intracellular Phosphate ◽  
Heart Preparation ◽  
Power Outputs

An in situ perfused heart preparation was used to study the effects of severe hypoxia in the rainbow trout, Oncorhynchus mykiss. Hypoxic trout hearts were capable of generating similar power outputs and ATP turnovers to normoxic counterparts at subphysiological work regimes. However, lactate efflux was 35-fold higher and glycolytic rate was calculated to be > 10-fold higher in hypoxic than in normoxic hearts. The surprising ability of trout hearts to withstand severe hypoxia appears to be related to the rapid removal of lactate and associated protons from the heart. An increase in power demand to normal in vivo levels caused rapid failure in hypoxic hearts. Failure was caused by a decline in stroke volume (contractility) and was not a consequence of heart rate deterioration. Hypoxia caused marked declines in the concentration of creatine phosphate but not ATP, and we suggest that an increase in intracellular phosphate was the primary cause of failure.

Respiratory activity, molar growth yields, and ATP content in an Arthrobacter sp. ammonium-limited chemostat culture

1983 ◽  
Vol 29 (9) ◽  
pp. 1136-1140 ◽  
Author(s):  
I. Cacciari ◽  
D. Lippi ◽  
S. Ippoliti ◽  
W. Pietrosanti
Keyword(s):  
Respiratory Activity ◽  
Chemostat Culture ◽  
Morphological Changes ◽  
Sharp Decrease ◽  
Growth Yields ◽  
Atp Content ◽  
Lower Growth ◽  
Wide Range ◽  
Metabolic Activities

Arthrobacter fluorescens was grown in chemostat culture under ammonium-limited conditions and respiratory activity; molar growth yields and ATP content were determined over a wide range of dilution rates. Within a range of dilution rates between 0.10 h−1 and 0.20 h−1, morphological transition occurred, the ratio of cocci to rods appearing inversely related to growth rate. Molar growth yields for both glucose and ammonium decreased with increasing dilution rates because of the higher intracellular polysaccharide content at the lower growth rates. Different metabolic activities were shown in cocci, in rods, and during morphogenesis. A sharp decrease in in situ and potential oxygen quotient (Q(O2)) and in ATP content was observed in the range of dilution rates in which morphological changes occurred.

Maintenance of eupnea of in situ and in vivo rats following riluzole: A blocker of persistent sodium channels

2007 ◽  
Vol 155 (1) ◽  
pp. 97-100 ◽  
Author(s):  
Walter M. St.-John ◽  
Hidefumi Waki ◽  
Mathias Dutschmann ◽  
Julian F.R. Paton
Keyword(s):  
Sodium Channels
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