Capillary Pericyte KATP Channel Activation Drives the Dilation of Upstream Cerebral Arterioles

We investigated the effects of various amino acids on responses to ATP-sensitive potassium (KATP) channel openers in anesthetized cats equipped with cranial windows. The application of pinacidil by superfusion caused transient vasodilation, whereas there was sustained vasodilation from the application of stationary solution of pinacidil. In the presence ofl-arginine orl-lysine, pinacidil by superfusion led to sustained vasodilation, suggesting that the rapid flow of fluid displaced these amino acids from binding on the channel and that such binding was essential for opening the channel. N G-nitro-l-arginine blocked responses to pinacidil, and this blockade was reversed byl-lysine orl-arginine but not byd-arginine,d-lysine, methyl-l-arginine, glycine,l-histidine, dimethylarginine, dimethyl-l-arginine, or hydroxylysine. The blockade of responses to pinacidil induced by glyburide was also reversed completely byl-arginine orl-lysine but not byd-arginine, suggesting that these amino acids act on the sulfonylurea receptor. Hydroxylysine but not methyl-l-lysine, dimethylarginine, or dimethyl-l-arginine blocked responses to pinacidil. The findings show that KATP channels in cerebral arterioles need l-lysine orl-arginine to open in response to agonists.

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52. Antipsychotics Perturb Glucose Homeostasis by Inhibiting Hypothalamic KATP Channel Activation

Biological Psychiatry ◽

10.1016/j.biopsych.2019.03.066 ◽

2019 ◽

Vol 85 (10) ◽

pp. S21-S22

Author(s):

Chantel Kowalchuk ◽

Laura Castellani ◽

Celine Teo ◽

Pruntha Kanagasundaram ◽

William Brett McIntyre ◽

...

Keyword(s):

Glucose Homeostasis ◽

Katp Channel ◽

Channel Activation

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Mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone induces vasorelaxation without involving KATP channel activation in smooth muscle cells of arteries

British Journal of Pharmacology ◽

10.1111/bph.13578 ◽

2016 ◽

Vol 173 (21) ◽

pp. 3145-3158 ◽

Cited By ~ 16

Author(s):

Yan-Qiu Zhang ◽

Xin Shen ◽

Xiao-Lin Xiao ◽

Ming-Yu Liu ◽

Shan-Liang Li ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Katp Channel ◽

Muscle Cells ◽

Channel Activation ◽

Carbonyl Cyanide ◽

Mitochondrial Uncoupler

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Relationship among NO, the KATP channel, and opioids in hypoxic pial artery dilation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.275.3.h988 ◽

1998 ◽

Vol 275 (3) ◽

pp. H988-H994 ◽

Cited By ~ 6

Author(s):

William M. Armstead

Keyword(s):

Katp Channel ◽

No Synthase ◽

Channel Activation ◽

Cranial Window ◽

Pial Artery ◽

Sequential Release ◽

No Release ◽

Before And After ◽

Newborn Pigs ◽

Synthase Inhibitor

Nitric oxide (NO), opioids, and ATP-sensitive K+(KATP) channel activation contribute to hypoxia-induced pial artery dilation. NO releasers and cGMP analogs increase opioid concentration in cerebrospinal fluid (CSF) and elicit dilation via KATPchannel activation. Opioids themselves also elicit dilation via KATP channel activation. This study was designed to investigate the relationships among the above mechanisms in hypoxic pial artery dilation using newborn pigs equipped with a closed cranial window. Cromakalim (10−8 and 10−6 M), a KATP agonist, produced dilation that was unchanged by the NO synthase inhibitor N-nitro-l-arginine (l-NNA, 10−6 and 10−3 M): 13 ± 1 and 31 ± 1 vs. 14 ± 1 and 31 ± 1% before and after 10−3 Ml-NNA. Cromakalim dilation also was not associated with increased CSF cGMP and was unchanged by the Rp diastereomer of 8-bromoguanosine 3′,5′-cyclic monophosphothioate, a cGMP antagonist. Glibenclamide (10−6 M), a KATP antagonist, attenuated hypoxic dilation but hypoxia-associated CSF cGMP release was unchanged: 457 ± 12 and 935 ± 30 vs. 458 ± 11 and 921 ± 22 fmol/ml. Coadministration ofl-NNA with glibenclamide had no further effect on the already diminished hypoxic dilation but blocked the hypoxia-associated rise in CSF cGMP. Cromakalim had no effect on CSF methionine enkephalin: 1,012 ± 28 and 1,062 ± 32 pg/ml. These data show that KATP channel agonists do not elicit dilation via NO/cGMP and do not release opioids. NO release during hypoxia also is independent of KATP channel activation. These data suggest that hypoxic dilation results from the sequential release of NO, cGMP, and opioids, which in turn activate the KATP channel.

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Erratum: KATP Channel Activation Mediates Nicorandil-Induced Relaxation of Nitrate-Tolerant Coronary Arteries

Journal of Cardiovascular Pharmacology ◽

10.1097/00005344-199610000-00020 ◽

1996 ◽

Vol 28 (4) ◽

pp. 603

Author(s):

&NA;

Keyword(s):

Coronary Arteries ◽

Katp Channel ◽

Channel Activation

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ROS and NO trigger early preconditioning: relationship to mitochondrial KATP channel

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00706.2002 ◽

2003 ◽

Vol 284 (1) ◽

pp. H299-H308 ◽

Cited By ~ 158

Author(s):

Gilles Lebuffe ◽

Paul T. Schumacker ◽

Zuo-Hui Shao ◽

Travis Anderson ◽

Hirotoro Iwase ◽

...

Keyword(s):

Nitric Oxide ◽

Reactive Oxygen Species ◽

Methyl Ester ◽

Katp Channel ◽

Channel Blocker ◽

No Synthase ◽

Oxygen Species ◽

Channel Activation ◽

Mitochondrial Katp Channel ◽

The Relationship

Reactive oxygen species (ROS) and nitric oxide (NO) are implicated in induction of ischemic preconditioning. However, the relationship between these oxidant signals and opening of the mitochondrial ATP-dependent potassium (KATP) channel during early preconditioning is not fully understood. We observed preconditioning protection by hypoxia, exogenous H2O2, or PKC activator PMA in cardiomyocytes subjected to 1-h ischemia and 3-h reperfusion. Protection was abolished by KATP channel blocker 5-hydroxydecanoate (5-HD) in each case, indicating that these triggers must act upstream from the KATP channel. Inhibitors of NO synthase abolished protection in preconditioned cells, suggesting that NO is also required for protection. DAF-2 fluorescence (NO sensitive) increased during hypoxic triggering. This was amplified by pinacidil and inhibited by 5-HD, indicating that NO is generated subsequent to KATP channel activation. Exogenous NO during the triggering phase conferred protection blocked by 5-HD. Exogenous NO also restored protection abolished by 5-HD or N ω-nitro-l-arginine methyl ester in preconditioned cells. Antioxidants given during pinacidil or NO triggering abolished protection, confirming that ROS are generated by KATP channel activation. Coadministration of H2O2 and NO restored PMA-induced protection in 5-HD-treated cells, indicating that ROS and NO are required downstream from the KATP channel. We conclude that ROS can trigger preconditioning by causing activation of the KATP channel, which then induces generation of ROS and NO that are both required for preconditioning protection.

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

Anesthesiology ◽

10.1097/00000542-200408000-00021 ◽

2004 ◽

Vol 101 (2) ◽

pp. 399-408 ◽

Cited By ~ 17

Author(s):

Jeffrey B. Musser ◽

Timothy B. Bentley ◽

Scott Griffith ◽

Pushpa Sharma ◽

John E. Karaian ◽

...

Keyword(s):

Nitric Oxide ◽

Mean Arterial Pressure ◽

Nitric Oxide Synthase ◽

Hemorrhagic Shock ◽

Inducible Nitric Oxide Synthase ◽

Katp Channel ◽

Channel Activation ◽

Oxide Synthase ◽

Nitric Oxide Synthase Activity ◽

Inducible Nitric Oxide

Background To determine the role of nitric oxide and adenosine triphosphate-sensitive potassium (KATP) vascular channels in vascular decompensation during controlled hemorrhagic shock in swine. Methods Thirty instrumented, anesthetized adolescent Yorkshire swine were subjected to controlled isobaric hemorrhage to a mean arterial pressure of 40 mmHg for 2 h (n = 6) or 4 h (n = 10) or 50 mmHg for 4 h (n = 8). An additional six animals were used as anesthetized instrumented time controls. During controlled hemorrhage, plasma and tissue samples were obtained every 30 to 60 min. Before euthanasia, tissue (carotid artery, lung, liver, and aorta) was obtained for analysis of nitrate concentrations and nitric oxide synthase activity. Isolated carotid artery ring reactivity to norepinephrine was also determined with and without glibenclamide. Results Animals hemorrhaged to 40 mmHg decompensated earlier than animals hemorrhaged to 50 mmHg. Plasma nitrate concentrations and nitric oxide synthase activity rose consistently throughout hemorrhage in both groups. However, they were substantially higher in the mean arterial pressure 40 group. Constitutive nitric oxide synthase activity was the major contributor to total nitric oxide synthase activity throughout the protocol with only the animals maintained at 40 mmHg for 4 h showing evidence of inducible nitric oxide synthase activity. Profound KATP channel activation and hyporeactivity of isolated vessel rings to norepinephrine was not observed until 4 h after the initiation of hemorrhagic shock. Only those animals with inducible nitric oxide synthase activity showed a decreased response to norepinephrine, and this hyporeactivity was reversed with the KATP channel inhibitor, glibenclamide. Conclusions 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.

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