Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension

Li, Melissa W.; Dai, Xiaoling; Watts, Stephanie W.; Kreulen, David L.; Fink, Gregory D.

doi:10.1152/ajpregu.00783.2007

Cited by 9 publications

(10 citation statements)

References 63 publications

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“…Related to this finding are previous results demonstrating a selective activation of sympathetic vasomotor tone to the splanchnic vascular bed indicating differential sympathetic activation by S6c (Li et al. ). The absence of a change in HR suggests that postganglionic cardiac sympathetic neurons in our model may not be influenced by ET B receptor activation particularly at low doses of S6c.…”

Section: Discussionsupporting

confidence: 75%

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Activation of neuronal endothelin B receptors mediates pressor response through alpha-1 adrenergic receptors

et al. 2017

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Abnormalities in activity of the endothelin (ET) system have been widely reported in a number of cardiovascular disease states such as hypertension and heart failure. Although the vascular responses to ET are well established, the interaction between ET and other important modulators of blood pressure, such as the sympathetic nervous system, are less understood. Previous reports implicate ET signaling through ET type B (ETB) receptors in increasing neuronal activity. Therefore, we hypothesized that activation of ETB receptors on sympathetic nerves would increase blood pressure through an adrenergic‐mediated mechanism. Thus, we used anesthetized ETB‐deficient rats, which only express functional ETB receptors on adrenergic neurons, and genetic controls, which express functional ETB receptors in vascular tissue and kidney epithelium. We determined the pressor response to the selective ETB receptor agonist sarafotoxin c (S6c). Separate groups of rats were treated with the α 1‐adrenergic receptor antagonist prazosin or the β‐adrenergic receptor antagonist propranolol to elucidate the role of adrenergic signaling in mediating the blood pressure response. We observed a dose‐dependent pressor response to S6c in ETB‐deficient rats that was reversed by prazosin treatment and augmented by propranolol. In genetic control rats, the effects of S6c on sympathetic neurons were mostly masked by the direct activity of ETB receptor activation on the vasculature. Heart rate was mostly unaffected by S6c across all groups and treatments. These results suggest that ETB activation on sympathetic neurons causes an increase in blood pressure mediated through α 1‐adrenergic receptor signaling.

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Section: Discussionsupporting

confidence: 75%

“…, ; Li et al. ; Kopp et al. ), yet direct evidence connecting ET B receptors and sympathetic activity in modulating blood pressure is lacking.…”

Section: Introductionmentioning

confidence: 99%

Activation of neuronal endothelin B receptors mediates pressor response through alpha-1 adrenergic receptors

et al. 2017

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“…We recognize that the inability to directly probe the ET B receptor is a limitation of our study. A role for both ET A and ET B receptors in stimulating ROS in the vasculature and sympathetic nervous system is supported by previously published studies 34–35, 53, 54. Alternatively, the two receptor subtypes may functionally interact to produce an increase in ROS 8…”

Section: Discussionmentioning

confidence: 62%

Endothelin Activation of Reactive Oxygen Species Mediates Stress-Induced Pressor Response in Dahl Salt-Sensitive Prehypertensive Rats

D’Angelo¹,

Loria²,

Pollock³

et al. 2010

Hypertension

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Abstract-Experiments were designed to test the hypothesis that endothelin (ET) and/or reactive oxygen species contribute to the pressor response induced by acute air jet stress in normotensive Dahl salt-sensitive rats maintained on a normal salt diet (prehypertensive). Mean arterial pressure was chronically monitored by telemetry before and after 3-day treatment with the free radical scavenger 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (Tempol) or ET receptor antagonists ABT-627 (ET A antagonist) or A-182086 (ET A/B antagonist) supplied in the drinking water. Rats were restrained and subjected to pulsatile air jet stress (3 minutes). Plasma samples at baseline and during acute stress were analyzed for 8-isoprostane (measure of reactive oxygen species production) and ET. Neither Tempol nor ET receptor antagonist treatment had an effect on baseline mean arterial pressure or plasma 8-isoprostane. The pressor response to acute stress was accompanied by significant increases in plasma 8-isoprostane and ET. Tempol significantly reduced both the total pressor response (area under the curve) and the stress-mediated increase in plasma 8-isoprostane; conversely, Tempol had no effect on the stress-induced increase in plasma ET. Combined ET A/B antagonism, but not selective ET A receptor blockade, similarly suppressed the pressor response to stress and stress-mediated rise in 8-isoprostane. Together these results indicate that reactive oxygen species contribute to the pressor response to acute air jet stress. Furthermore, the increase in reactive oxygen species occurs downstream of ET B receptor activation. (Hypertension. 2010;56:282-289.)Key Words: endothelin Ⅲ reactive oxygen species Ⅲ air jet stress Ⅲ Dahl salt-sensitive rat Ⅲ blood pressure R eactive oxygen species (ROS) contribute to the pathogenesis of cardiovascular dysfunction associated with several diseases, including hypertension, chronic heart failure, ischemic heart disease, hyperlipidemia, and diabetes mellitus. [1][2][3] In addition, results from several laboratories suggest that ROS are implicated in normal cardiovascular function. Systemic administration of the free radical scavenger 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) leads to significant decreases in mean arterial pressure (MAP), heart rate (HR), and sympathetic nerve activity in normotensive animals, 4 -6 suggesting an important role for ROS in the regulation of arterial pressure. Studies performed in vitro 7,8 and in vivo 9,10 also demonstrate that ROS are involved in the constrictor or pressor response, respectively, to various agonists.A growing body of evidence suggests that behavioral stress elicits production of ROS; most of these reports, however, focus on chronic stress paradigms. 11,12 Numerous studies suggest that acute stress may induce cardiovascular dysfunction, [13][14][15][16][17][18][19][20] and additional studies have shown that cardiovascular hyperreactivity is strongly associated with future cardiovascular disease. [21][22][23][24][25][26][27][28] Proposed as a m...

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“…Nuclei were stained with 4'-6-Diamidino-2-phenylindole (DAPI) at a concentration of 10 µg/ml. In situ detection of superoxide was performed as described previously (33). Briefly, slides were placed into PBS for 30 min at room temperature and then stained with dihydroethidium (DHE, 10µM) in PBS for 60 min in a moist chamber in the dark.…”

Section: Methodsmentioning

confidence: 99%

gp-91 mediates histone deacetylase inhibition-induced cardioprotection

Zhao

Zhang

Cheng

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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We have recently shown that the inhibition of histone deacetylases (HDAC) protects the heart against ischemia and reperfusion (I/R) injury. The mechanism by which HDAC inhibition induces cardioprotection remains unknown. We sought to investigate whether the genetic disruption of gp-91, a subunit of NADPH-oxidase, would mitigate cardioprotection of HDAC inhibition. Wild-type and gp-91−/− mice were treated with a potent inhibitor of HDACs, trichostatin A (TSA, 0.1mg/kg, i.p.). Twenty-four hours later, the perfused hearts were subjected to 30 min of ischemia and 30 min of reperfusion. HDAC inhibition in wild-type mice produced marked improvements in ventricular functional recovery and the reduction of infarct size. TSA-induced cardioprotection was eliminated with genetic deletion of gp91. Notably, Western blot and immunostaining displayed a significant increase in gp-91 in myocardium following HDAC inhibition, which resulted in a mildly subsequent increase in the production of reactive oxygen species (ROS). The pretreatment of H9c2 cardiomyoblasts with TSA (50 nmol/L) decreased cell necrosis and increased viability in response to simulated ischemia (SI), which was abrogated by the transfection of cells with gp-91 siRNA, but not by scrambled siRNA. Furthermore, treatment of PLB-985 gp91+/+cells with TSA increased the resistance to SI, which also diminished with genetic disruption of gp91 in gp91phox-deficient PLB-985 cells. TSA treatment inhibited the increased active caspase-3 in H9c2 cardiomyoblasts and PLB-985 gp91+/+cells exposed to SI, which were prevented by knockdown of gp-91 by siRNA. These results suggest that a cascade consisting of gp-91 and HDAC inhibition plays an essential role in orchestrating the cardioprotective effect.

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Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension

Cited by 9 publications

References 63 publications

Activation of neuronal endothelin B receptors mediates pressor response through alpha-1 adrenergic receptors

Activation of neuronal endothelin B receptors mediates pressor response through alpha-1 adrenergic receptors

Endothelin Activation of Reactive Oxygen Species Mediates Stress-Induced Pressor Response in Dahl Salt-Sensitive Prehypertensive Rats

gp-91 mediates histone deacetylase inhibition-induced cardioprotection

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