Activation of Potassium Channels by Tempol in Arterial Smooth Muscle Cells From Normotensive and Deoxycorticosterone Acetate-Salt Hypertensive Rats

Xu, Hui; Jackson, William F.; Fink, Gregory D.; Galligan, James J.

doi:10.1161/01.hyp.0000249511.96555.57

Cited by 35 publications

(37 citation statements)

References 43 publications

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“…Tempol directly activates vascular Ca 2+ -activated potassium channels, modulating the vascular smooth muscle tone. 40 We found that a discrete vasodilation was induced by direct injection of tempol in MABs only when very high doses of the antioxidant were used (data not shown). The improvement in ACh-induced vasodilatory effect observed in our study was a result of chronic treatment with tempol, given that the vascular preparation was perfused with PSS without addition of the antioxidant.…”

Section: Discussionmentioning

confidence: 85%

Antioxidant Treatment With Tempol and Apocynin Prevents Endothelial Dysfunction and Development of Renovascular Hypertension

Costa

Amaral

Carvalho

et al. 2009

American Journal of Hypertension

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Section: Discussionmentioning

confidence: 85%

Antioxidant Treatment With Tempol and Apocynin Prevents Endothelial Dysfunction and Development of Renovascular Hypertension

Costa

Amaral

Carvalho

et al. 2009

American Journal of Hypertension

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“…Previous studies have shown that tempol is, in fact, sympathoinhibitory in hypertensive rats (17,24). A caveat to this conclusion, however, is that tempol also has other pharmacological effects [e.g., opening large conductance, calcium activated potassium channels (64)] and sites of action (e.g., blood vessels, kidney or brain) that could attenuate sympathetic activity and/or hypertension.…”

Section: Discussionmentioning

confidence: 98%

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

Dai

Watts

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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(ET BR) are expressed in multiple tissues and perform different functions depending on their location. ET BR mediate endothelium-dependent vasodilation, clearance of circulating ET, and diuretic effects; all of these should produce a fall in arterial blood pressure. However, we recently showed that chronic activation of ET BR in rats with the selective agonist sarafotoxin 6c (S6c) causes sustained hypertension. We have proposed that one mechanism of this effect is constriction of capacitance vessels. The current study was performed to determine whether S6c hypertension is caused by increased generation of reactive oxygen species (ROS) and/or activation of the sympathetic nervous system. The model used was continuous 5-day infusion of S6c into male Sprague-Dawley rats. No changes in superoxide anion levels in arteries and veins were found in hypertensive S6c-treated rats. However, superoxide levels were increased in sympathetic ganglia from S6c-treated rats. In addition, superoxide levels in ganglia increased progressively the longer the animals received S6c. Treatment with the antioxidant tempol impaired S6c-induced hypertension and decreased superoxide levels in ganglia. Acute ganglion blockade lowered blood pressure more in S6c-treated rats than in vehicle-treated rats. Although plasma norepinephrine levels were not increased in S6c hypertension, surgical ablation of the celiac ganglion plexus, which provides most of the sympathetic innervation to the splanchnic organs, significantly attenuated hypertension development. The results suggest that S6c-induced hypertension is partially mediated by sympathoexcitation to the splanchnic organs driven by increased oxidative stress in prevertebral sympathetic ganglia. endothelin type B receptor; oxidative stress; neuronal regulation WE RECENTLY REPORTED that chronic activation of endothelin (ET) type B receptors (ET B Rs) using intravenous infusion of the ET B R-selective agonist sarafotoxin 6c (S6c) in rats causes an increase in arterial pressure (S6c-induced hypertension) (16). This was surprising in light of the fact that the two best described physiological responses to ET B R activation, i.e., release of vasodilators from endothelial cells, and increased renal sodium and water excretion, should lead to a fall in arterial pressure (42,48,50). We believe venoconstriction contributes to S6c-induced hypertension, because in vitro S6c has been shown to constrict veins from most vascular regions but to have little effect on most arteries (15,27,41,49).It is likely, however, that other mechanisms contribute to S6c-induced hypertension. Reactive oxygen species (ROS) are a variety of oxygen-containing molecules that are by-products of cellular metabolic processes under physiological condition, including superoxide anion (O 2 Ϫ ), hydrogen peroxide (H 2 O 2 ), and hydroxyl ion (OH⅐). Recently, increasing evidence has shown that ROS can function as cellular signaling molecules (5). Increased ROS levels have been found in blood vessels, kidneys, and other tissues in many ex...

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“…While tempol has been widely used as a superoxide scavenger in physiological studies (11,19,48,55), this compound also possesses a property to open ATP-sensitive and Ca 2ϩ -activated K ϩ channels (7,52,53). Recently, tempol has been shown to suppress the exaggeration of the exercise pressor reflex in rats whose femoral artery had been ligated for 72 h independent of its antioxidant effects (32) but through its effect to open ATP-sensitive K ϩ channels (53).…”

Section: Methodsmentioning

confidence: 99%

Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II

Koba

Watanabe

Kano

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Koba S, Watanabe R, Kano N, Watanabe T. Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II. Am J Physiol Heart Circ Physiol 304: H142-H153, 2013. First published October 19, 2012 doi:10.1152/ajpheart.00423.2012.-Muscle contraction stimulates thin fiber muscle afferents and evokes reflex sympathoexcitation. In hypertension, this reflex is exaggerated. ANG II, which is elevated in hypertension, has been reported to trigger the production of superoxide and other reactive oxygen species. In the present study, we tested the hypothesis that increased ANG II in hypertension exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation by inducing oxidative stress in the muscle. In rats, subcutaneous infusion of ANG II at 450 ng·kg Ϫ1 ·min Ϫ1 for 14 days significantly (P Ͻ 0.05) elevated blood pressure compared with shamoperated (sham) rats. Electrically induced 30-s hindlimb muscle contraction in decerebrate rats with hypertension evoked larger renal sympathoexcitatory and pressor responses [ϩ1,173 Ϯ 212 arbitrary units (AU) and ϩ35 Ϯ 5 mmHg, n ϭ 10] compared with sham normotensive rats (ϩ419 Ϯ 103 AU and ϩ13 Ϯ 2 mmHg, n ϭ 11). Tempol, a SOD mimetic, injected intra-arterially into the hindlimb circulation significantly reduced responses in hypertensive rats, whereas this compound had no effect on responses in sham rats. Tiron, another SOD mimetic, also significantly reduced reflex renal sympathetic and pressor responses in a subset of hypertensive rats (n ϭ 10). Generation of muscle superoxide, as evaluated by dihydroethidium staining, was increased in hypertensive rats. RT-PCR and immunoblot experiments showed that mRNA and protein for gp91 phox , a NADPH oxidase subunit, in skeletal muscle tissue were upregulated in hypertensive rats. Taken together, hese results suggest that increased ANG II in hypertension induces oxidative stress in skeletal muscle, thereby exaggerating the muscle reflex. muscle contraction; angiotensin II; oxidative stress; sympathetic nerve activity HYPERTENSION is associated with an increased risk of cardiovascular disease (50). Antihypertensive treatments include increased physical activity or exercise (8, 23). It has been noted that in hypertension, the sympathoexcitation and elevation of blood pressure seen during exercise are excessive (10,39). This cardiovascular hyperexcitability is potentially dangerous because it can elevate risks for adverse cardiac events such as acute myocardial ischemia, myocardial infarction, left ventricular hypertrophy, or arrhythmia as well as stroke after a bout of exercise (23,36). Determining the causes underlying the hyperexcitability in this pathological condition is clinically important.A reflex originating in exercising skeletal muscle is activated as thin fiber muscle afferents (groups III and IV) are stimulated by mechanical deformation of the afferents' receptive fields as well as by metabolic byproducts during contraction (9, 33). In turn, afferent e...

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Activation of Potassium Channels by Tempol in Arterial Smooth Muscle Cells From Normotensive and Deoxycorticosterone Acetate-Salt Hypertensive Rats

Cited by 35 publications

References 43 publications

Antioxidant Treatment With Tempol and Apocynin Prevents Endothelial Dysfunction and Development of Renovascular Hypertension

Antioxidant Treatment With Tempol and Apocynin Prevents Endothelial Dysfunction and Development of Renovascular Hypertension

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

Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II

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