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Integrated control of coronary blood flow in exercising swine by adenosine, nitric oxide and K ATP channels
Author(s) -
Duncker Dirk J,
Beer Vincent J,
Taveerne Yannick,
Graaff Han,
Merkus Daphne
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1023.9
Subject(s) - glibenclamide , adenosine , vasodilation , medicine , adenosine receptor , cardiology , anesthesia , endocrinology , pharmacology , chemistry , receptor , diabetes mellitus , agonist
The mechanism of exercise‐induced coronary vasodilation remains incompletely understood. K ATP channels in conjunction with nitric oxide (NO) and adenosine have been proposed to mediate exercise hyperemia in dogs but not in swine. Different results may have been due, in part, to different routes of administration of drugs to block these pathways. Hence, we studied the role of K ATP channels together with NO and adenosine in exercise hyperemia in swine, using an identical drug dosing protocol and administration route that was previously shown to virtually abolish the exercise hyperemia in dogs. Swine exercised on a treadmill at 0–5 km/h, before and after blockade of K ATP channels (glibenclamide, 50 μg/kg/min intracoronary (ic)), in the absence or presence of blockade of adenosine receptors (8‐phenyltheophylline, 8PT, 5 mg/kg iv) and NO‐synthase (nitro‐L‐arginine, NLA, 1.5 mg/kg, ic). Glibenclamide reduced myocardial O 2 delivery and coronary venous O 2 tension at rest and during exercise. Administration of 8PT + NLA reduced coronary venous O 2 tension but did not enhance vasoconstriction to glibenclamide. Despite an increase in O 2 ‐extraction to ~90% during combined NLA + 8PT + glibenclamide, exercise‐induced hyperemia was maintained. Thus, K ATP channels, adenosine and NO do not appear to be critical for exercise coronary hyperemia, and act in a linear additive fashion, in swine. Supported by NHF Grant 2000T042