Effects of combined inhibition of ATP-sensitive potassium channels, nitric oxide, and prostaglandins on hyperemia during moderate exercise

• Published in: Journal of applied physiology (1985) Vol. 100; no. 5; pp. 1506 - 1512
• Main Authors: Schrage, William G, Dietz, Niki M, Joyner, Michael J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.05.2006; American Physiological Society
• Subjects: Adenosine; Adenosine Triphosphate - physiology; Adult; ATP; Biological and medical sciences; Enzyme Inhibitors - pharmacology; Exercise; Exercise - physiology; Female; Forearm - blood supply; Forearm - physiology; Fundamental and applied biological sciences. Psychology; Glyburide - pharmacology; Human subjects; Humans; Hyperemia - physiopathology; Inhibitor drugs; Ketorolac - pharmacology; Male; Muscle, Skeletal - blood supply; Muscle, Skeletal - physiopathology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - physiology; Potassium; Potassium Channels - drug effects; Potassium Channels - physiology; Prostaglandins - physiology; Regional Blood Flow - drug effects; Regional Blood Flow - physiology; Ultrasonic imaging; Vasodilation - drug effects; Vasodilation - physiology; Young adults; Physical exercise; Prostaglandin-endoperoxide synthase; NG-nitro-L-arginine methyl ester; Ionic channel; Inorganic element; Doppler ultrasound; Arginine; Eicosanoid; Inhibition; nitric oxide synthase; Ultrasound; Human; Prostaglandin; Enzyme; Arachidonic acid derivatives; cyclooxygenase; Nitric-oxide synthase; Blood flow; Vertebrata; Mammalia; Aminoacid; Nitric oxide; Hemodynamics; Oxidoreductases; ATP; Potassium
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.01639.2005

1 Department of Anesthesiology and 2 General Clinical Research Center, Mayo Clinic, Rochester, Minnesota Submitted 30 December 2005 ; accepted in final form 6 February 2006 ATP-sensitive potassium (K ATP ) channels have been suggested to contribute to coronary and skeletal muscle vasodilation during exercise, either alone or interacting in a parallel or redundant process with nitric oxide (NO), prostaglandins (PGs), and adenosine. We tested the hypothesis that K ATP channels, alone or in combination with NO and PGs, regulate exercise hyperemia in forearm muscle. Eighteen healthy young adults performed 20 min of moderate dynamic forearm exercise, with forearm blood flow (FBF) measured via Doppler ultrasound. After steady-state FBF was achieved for 5 min (saline control), the K ATP inhibitor glibenclamide (Glib) was infused into the brachial artery for 5 min (10 µg·dl –1 ·min –1 ), followed by saline infusion during the final 10 min of exercise ( n = 9). Exercise increased FBF from 71 ± 11 to 239 ± 24 ml/min, and FBF was not altered by 5 min of Glib. Systemic plasma Glib levels were above the therapeutic range, and Glib increased insulin levels by 50%, whereas blood glucose was unchanged (88 ± 2 vs. 90 ± 2 mg/dl). In nine additional subjects, Glib was followed by combined infusion of N G -nitro- L -arginine methyl ester ( L -NAME) plus ketorolac (to inhibit NO and PGs, respectively). As above, Glib had no effect on FBF but addition of L -NAME + ketorolac (i.e., triple blockade) reduced FBF by 15% below steady-state exercise levels in seven of nine subjects. Interestingly, triple blockade in two subjects caused FBF to transiently and dramatically decrease. This was followed by an acute recovery of flow above steady-state exercise values. We conclude 1 ) opening of K ATP channels is not obligatory for forearm exercise hyperemia, and 2 ) triple blockade of NO, PGs, and K ATP channels does not reduce hyperemia more than the inhibition of NO and PGs in most subjects. However, some subjects are sensitive to triple blockade, but they are able to restore FBF acutely during exercise. Future studies are required to determine the nature of these compensatory mechanisms in the affected individuals. Doppler ultrasound; N G -nitro- L -arginine methyl ester; blood flow; human; potassium; nitric oxide synthase; cyclooxygenase Address for reprint requests and other correspondence: W. G. Schrage, Dept. of Anesthesiology, Joseph 4-184W, Mayo Clinic, Rochester, MN 55905 (e-mail: schrage.william{at}mayo.edu )