Effects of U-37883A, a vascular selective KATP+ channel antagonist, in the pulmonary and hindlimb circulation

DeWitt, Bracken J.; Cheng, David Y.; McMahon, Timothy J.; Marrone, James R; Champion, Hunter C.; Kandowitz, P. J.

doi:10.1152/ajplung.1996.271.6.l924

Cited by 10 publications

(16 citation statements)

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“…Our findings are also consistent with experimental data in animals using a variety of techniques [18][19][20][21][22][23], which also suggest that vascular K ATP channels may not be critical to the regulation of basal vascular tone in skeletal muscle vasculature. Since the measurement of blood flow by forearm strain gauge plethysmography primarily reflects skeletal muscle perfusion, our findings have relevance to the skeletal muscle vascular bed.…”

Section: K Atp Channels and Resting Skeletal Muscle Blood Flowsupporting

confidence: 89%

Effects of inhibition of ATP-sensitive potassium channels on metabolic vasodilation in the human forearm

Farouque

Meredith

2002

Clinical Science

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Experimental data suggest that vascular ATP-sensitive potassium (K(ATP)) channels may be an important determinant of functional hyperaemia, but the contribution of K(ATP) channels to exercise-induced hyperaemia in humans is unknown. Forearm blood flow was assessed in 39 healthy subjects (23 males/16 females; age 22+/-4 years) using the technique of venous occlusion plethysmography. Resting forearm blood flow and functional hyperaemic blood flow (FHBF) were measured before and after brachial artery infusion of the K(ATP) channel inhibitors glibenclamide (at two different doses: 15 and 100 microg/min) and gliclazide (at 300 microg/min). FHBF was induced by 2 min of non-ischaemic wrist flexion-extension exercise at 45 cycles/min. Compared with vehicle (isotonic saline), glibenclamide at either 15 microg/min or 100 microg/min did not significantly alter resting forearm blood flow or peak FHBF. The blood volume repaid at 1 and 5 min after exercise was not diminished by glibenclamide. Serum glucose was unchanged after glibenclamide, but plasma insulin rose by 36% (from 7.2+/-0.8 to 9.8+/-1.3 m-units/l; P =0.02) and 150% (from 9.1+/-1.3 to 22.9+/-3.5 m-units/l; P =0.002) after the 15 and 100 microg/min infusions respectively. Gliclazide also did not affect resting forearm blood flow, peak FHBF, or the blood volume repaid at 1 and 5 min after exercise, compared with vehicle (isotonic glucose). Gliclazide induced a 12% fall in serum glucose (P =0.009) and a 38% increase in plasma insulin (P =0.001). Thus inhibition of vascular K(ATP) channels with glibenclamide or gliclazide does not appear to affect resting forearm blood flow or FHBF in healthy humans. These findings suggest that vascular K(ATP) channels may not play an important role in regulating basal vascular tone or skeletal muscle metabolic vasodilation in the forearm of healthy human subjects.

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Section: K Atp Channels and Resting Skeletal Muscle Blood Flowsupporting

confidence: 89%

Effects of inhibition of ATP-sensitive potassium channels on metabolic vasodilation in the human forearm

Farouque

Meredith

2002

Clinical Science

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“…Meisheri et al (78) and many others (16,27,28,54,69,97,99,108) have confirmed that, consistent with its in vitro profile, PNU-37883A antagonizes the hypotensive and vasodilatory effects of chemically different K-ATP channel openers in intact animals. In anesthetized cats, PNU-37883A (3.3 mg/kg i.v.)…”

Section: In Vivo K-atp Channel Opener Reversal and Interactionsmentioning

confidence: 68%

“…; 54), whereas a more natriuretic dose of 10 mg/kg transiently increased blood pressure and reduced heart rate (52). Compared with these species, in anesthetized cats K-ATP blocking doses of PNU-37883A (Յ5 mg/kg) minimally affected basal blood pressure, heart rate, or vascular resistance (16)(17)(18)(19)27,28,78,99).…”

Section: In Vivo Cardiovascular Actionsmentioning

confidence: 99%

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Pharmacology of the K‐ATP Channel Blocking Morpholinoguanidine PNU‐37883A

Humphrey

1999

Cardiovascular Drug Reviews

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“…Glibenclamide can also increase resistance in the mesenteric and renal vasculature, and in some skeletal muscle preparations [146][147][148]. However K ATP channels appear to make little contribution to resting tone in the pulmonary or cerebral circulations [141,[149][150][151].…”

Section: Functional Rolesmentioning

confidence: 99%

ATP-Sensitive Potassium Channels

Rodrigo

Standen²

2005

CPD

104

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ATP-sensitive potassium (K(ATP)) channels link membrane excitability to metabolism. They are regulated by intracellular nucleotides and by other factors including membrane phospholipids, protein kinases and phosphatases. K(ATP) channels comprise octamers of four Kir6 pore-forming subunits associated with four sulphonylurea receptor subunits. The exact subunit composition differs between the tissues in which the channels are expressed, which include pancreas, cardiac, smooth and skeletal muscle and brain. K(ATP) channels are targets for antidiabetic sulphonylurea blockers, and for channel opening drugs that are used as antianginals and antihypertensives. This review focuses on non-pancreatic K(ATP) channels. In vascular smooth muscle, K(ATP) channels are extensively regulated by signalling pathways and cause vasodilation, contributing both to resting blood flow and vasodilator-induced increases in flow. Similarly, K(ATP) channel activation relaxes smooth muscle of the bladder, gastrointestinal tract and airways. In cardiac muscle, sarcolemmal K(ATP) channels open to protect cells under stress conditions such as ischaemia or exercise, and appear central to the protection induced by ischaemic preconditioning (IPC). Mitochondrial K(ATP) channels are also strongly implicated in IPC, but clarification of their exact role awaits information on their molecular structure. Skeletal muscle K(ATP) channels play roles in fatigue and recovery, K+ efflux, and glucose uptake, while neuronal channels may provide ischaemic protection and underlie the glucose-responsiveness of hypothalamic neurones. Current therapeutic considerations include the use of K(ATP) openers to protect cardiac muscle, attempts to develop openers selective for airway or bladder, and the question of whether block of extra-pancreatic K(ATP) channels may cause adverse cardiovascular side-effects of sulphonylureas.

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Effects of U-37883A, a vascular selective KATP+ channel antagonist, in the pulmonary and hindlimb circulation

Cited by 10 publications

References 0 publications

Effects of inhibition of ATP-sensitive potassium channels on metabolic vasodilation in the human forearm

Effects of inhibition of ATP-sensitive potassium channels on metabolic vasodilation in the human forearm

Pharmacology of the K‐ATP Channel Blocking Morpholinoguanidine PNU‐37883A

ATP-Sensitive Potassium Channels

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