Hemorrhagic Shock in Swine: Nitric Oxide and Potassium Sensitive Adenosine Triphosphate Channel Activation

Musser, Jeffrey M.B.; Bentley, Timothy B.; Griffith, Scott; Sharma, Pushpa; Karaian, John; Mongan, Paul D.

doi:10.1097/00000542-200408000-00021

Cited by 23 publications

(12 citation statements)

References 30 publications

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“…In this regard, it has been shown that ATP concentration decreases in the late stage of HS and that K ATP channel activation ensues, 41,42 which could also be contributing to membrane hyperpolarization. 15,16,[43][44][45] Previous work by us and others has also shown that K ATP activation contributes to the large membrane hyperpolarization in ASMCs from shock animals 14 -16,44,45 and that K ATP inhibition by glibenclamide restores the vascular reactivity to some extent. 16 In summary, we have demonstrated an enhanced coupling efficiency between Ca 2ϩ sparks and BK Ca in ASMCs from shock animals.…”

Section: Discussionmentioning

confidence: 88%

Hypersensitivity of BK _Ca to Ca ²⁺ Sparks Underlies Hyporeactivity of Arterial Smooth Muscle in Shock

Zhao

Pan

et al. 2007

Circulation Research

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Abstract-Large conductance Ca 2ϩ -activated K ϩ channels (BK Ca ) play a critical role in blood pressure regulation by tuning the vascular smooth muscle tone, and hyposensitivity of BK Ca to Ca 2ϩ sparks resulting from its altered ␤1 subunit stoichiometry underlies vasoconstriction in animal models of hypertension. Here we demonstrate hypersensitivity of BK Ca to Ca 2ϩ sparks that contributes to hypotension and blunted vasoreactivity in acute hemorrhagic shock. In arterial smooth muscle cells under voltage-clamp conditions (0 mV), the amplitude and duration, but not the frequency, of spontaneous transient outward currents of BK Ca origin were markedly enhanced in hemorrhagic shock, resulting in a 265% greater hyperpolarizing current. Concomitantly, subsurface Ca 2ϩ spark frequency was either unaltered (at 0 mV) or decreased in hyperpolarized resting cells. Examining the relationship between spark and spontaneous transient outward current amplitudes revealed a hypersensitive BK Ca activity to Ca 2ϩ spark in hemorrhagic shock, whereas the spark-spontaneous transient outward current coupling fidelity was near unity in both groups. Importantly, we found an acute upregulation of the ␤1 subunit of the channel, and single-channel recording substantiated BK Ca hypersensitivity at micromolar Ca 2ϩ , which promotes the ␣ and ␤1 subunit interaction. Treatment of shock animals with the BK Ca inhibitors iberiotoxin and charybdotoxin partially restored vascular membrane potential and vasoreactivity to norepinephrine and blood reinfusion. Thus, the results underscore a dynamic regulation of the BK Ca -Ca 2ϩ spark coupling and its therapeutic potential in hemorrhagic shock-associated vascular disorders. sparks beneath the plasma membrane activate 10 to 100 large conductance Ca 2ϩ -activated K ϩ channels (BK Ca ) in the adjacent sarcolemma and elicit the discharge of spontaneous transient outward currents (STOCs), resulting in membrane hyperpolarization and, subsequently, dilation of vascular smooth muscle. 3,4 Recent studies have revealed that the coupling between sparks and STOCs can continuously regulate, by negative feedback, the vascular tone in intact arteries. 5-8 Furthermore, it has been recently shown that the spark-STOC coupling efficiency is altered during hypertension, because of modulation of the subunit stoichiometry of BK Ca in vascular smooth muscle. 5 Severe shock is well characterized by a sequence of events, including release of endogenous vasoconstrictors, delayed vascular decompensation, and refractory hypotension that is defined as a progressive vasodilatation, as well as a continuous decrease in peripheral vascular resistance resulting in death, despite augmentation of sympathetic nervous activity or treatment with vasoconstrictors. 9 Various factors, such as ␣-adrenoceptor desensitization, metabolic acidosis, cytokine release, transcription factor activation, endothelial cell (EC) damage, and overproduction of nitric oxide (NO) have been shown to be involved in this process. 10 -13 Nevertheless, the ...

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Section: Discussionmentioning

confidence: 88%

Hypersensitivity of BK _Ca to Ca ²⁺ Sparks Underlies Hyporeactivity of Arterial Smooth Muscle in Shock

Zhao

Pan

et al. 2007

Circulation Research

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“…[17] The physiological antagonism between nitric oxide and angiotensin II, which has already been demonstrated in rats [18] and later in pigs, shows an association between activated K + ATP channels and nitric oxide. [19] The recovery of mean arterial blood pressure in hemorrhagic shock treated with K + ATP channel inhibitors has already been reported in rats [20] but was not seen under the acute conditions of this study.…”

Section: Discussionmentioning

confidence: 45%

Glibenclamide Effects on Renal Function and Histology after Acute Hemorrhage in Rats under Sevoflurane Anesthesia

et al. 2007

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Introduction. Hypovolemia from hemorrhage evokes protective compensatory reactions, such as the renin-angiotensin system, which interferes in the clearance function and can lead to ischemia. This study was designed to evaluate the effects of glibenclamide, a K + ATP channel blocker, on renal function and histology in rats in a state of hemorrhagic shock under sevoflurane anesthesia. Material and Methods. Twenty Wistar rats were randomized into two groups of 10 animals each (G1 and G2), only one of which (G2) received intravenous glibenclamide (1 μg.g −1 ), 60 min before bleeding was begun. Both groups were anesthetized with sevoflurane and kept on spontaneous respiration with oxygen-air, while being bled of 30% of volemia in three stages with 10 min intervals. There was an evaluation of renal function-sodium para-aminohippurate and iothalamate clearances, filtration fraction, renal blood flow, renal vascular resistance-and renal histology. Renal function attributes were evaluated at three moments: M1 and M2, coinciding with the first and third stages of bleeding; and M3, 30 min after M2, when the animals were subjected to bilateral nephrectomy before being sacrificed. Results. Significant differences were found in paraaminohippurate clearance, G1 < G2, and higher renal vascular resistance values were observed in G1. Histological examination showed the greater vulnerability of kidneys exposed to sevoflurane alone (G1) with higher scores of vascular and tubular dilatation. There were vascular congestion and tubular vacuolization only in G1. Necrosis and signs of tubular regeneration did not differ in both groups. Conclusion. Treatment with glibenclamide attenuated acutely the renal histological changes after hemorrhage in rats under sevoflurane anesthesia.

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“…The mechanism of action is not well understood but may result from inactivation of K ϩ currents that normally develop in vascular smooth muscle cells during metabolic acidosis (18). Reversal of these K ϩ currents has been suggested as a means by which vascular sensitivity to catecholamines is reestablished by AVP infusion in decompensated shock (25). In the present study, drug intervention was begun prior to decompensation.…”

Section: Discussionmentioning

confidence: 91%

The spleen is required for 5-HT_1Areceptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat

Tiniakov¹,

Scrogin²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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The 5-HT(1A) receptor agonist, 8- OH-DPAT, increases whole body venous tone (mean circulatory filling pressure; MCFP), and attenuates metabolic acidosis in a rat model of unresuscitated hemorrhagic shock. To determine whether improved acid-base balance was associated with sympathetic activation and venous constriction, MCFP, sympathetic activity (SA), and blood gases were compared in hemorrhaged rats following administration of 5-HT(1A) receptor agonist 8-OH-DPAT, the arterial vasoconstrictor arginine vasopressin (AVP), or saline. To further determine whether protection of acid-base balance was dependent on splenic contraction and blood mobilization, central venous pressure (CVP), MCFP, and blood gases were determined during hemorrhage and subsequent 8-OH-DPAT-administration in rats subjected to real or sham splenectomy. Subjects were hemorrhaged to an arterial pressure of 50 mmHg for 25 min and subsequently were treated with 8-OH-DPAT (30 nmol/kg iv), AVP titrated to match the pressor effect of 8-OH-DPAT (approximately 2 ng/min iv), or infusion of normal saline. 8-OH-DPAT increased MAP, CVP, MCFP, and SA, and decreased lactate accumulation. AVP did not affect CVP or SA, but raised MCFP slightly to a level intermediate between 8-OH-DPAT- and saline-treated rats. Infusion of AVP also produced a modest protection against metabolic acidosis. Splenectomy prevented the rise in CVP, MCFP, and protection against metabolic acidosis produced by 8-OH-DPAT but had no effect on the immediate pressor response to the drug. Together, the data indicate that 8-OH-DPAT produces a pattern of cardiovascular responses consistent with a sympathetic-mediated venoconstriction that is, in part, responsible for the drug's beneficial effect on acid-base balance. Moreover, blood mobilization stimulated by the spleen is required for the beneficial effects of 8-OH-DPAT.

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Hemorrhagic Shock in Swine: Nitric Oxide and Potassium Sensitive Adenosine Triphosphate Channel Activation

Abstract: The data indicate that profound KATP activation associated with increased nitric oxide concentrations and inducible nitric oxide synthase induction is a key factor in vascular smooth muscle hyporeactivity characteristic of the late decompensatory phase of hemorrhagic shock in swine.

Cited by 23 publications

References 30 publications

Hypersensitivity of BK _Ca to Ca ²⁺ Sparks Underlies Hyporeactivity of Arterial Smooth Muscle in Shock

Hypersensitivity of BK _Ca to Ca ²⁺ Sparks Underlies Hyporeactivity of Arterial Smooth Muscle in Shock

Glibenclamide Effects on Renal Function and Histology after Acute Hemorrhage in Rats under Sevoflurane Anesthesia

The spleen is required for 5-HT_1Areceptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat

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Hemorrhagic Shock in Swine: Nitric Oxide and Potassium Sensitive Adenosine Triphosphate Channel Activation

Abstract: The data indicate that profound KATP activation associated with increased nitric oxide concentrations and inducible nitric oxide synthase induction is a key factor in vascular smooth muscle hyporeactivity characteristic of the late decompensatory phase of hemorrhagic shock in swine.

Cited by 23 publications

References 30 publications

Hypersensitivity of BK Ca to Ca 2+ Sparks Underlies Hyporeactivity of Arterial Smooth Muscle in Shock

Hypersensitivity of BK Ca to Ca 2+ Sparks Underlies Hyporeactivity of Arterial Smooth Muscle in Shock

Glibenclamide Effects on Renal Function and Histology after Acute Hemorrhage in Rats under Sevoflurane Anesthesia

The spleen is required for 5-HT1Areceptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat

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Resources

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Hypersensitivity of BK _Ca to Ca ²⁺ Sparks Underlies Hyporeactivity of Arterial Smooth Muscle in Shock

Hypersensitivity of BK _Ca to Ca ²⁺ Sparks Underlies Hyporeactivity of Arterial Smooth Muscle in Shock

The spleen is required for 5-HT_1Areceptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat