Integrated control of coronary blood flow in exercising swine by adenosine, nitric oxide and KATP channels

Abstract

The mechanism of exercise‐induced coronary vasodilation remains incompletely understood. KATP 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 KATP 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 KATP 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 O2 delivery and coronary venous O2 tension at rest and during exercise. Administration of 8PT + NLA reduced coronary venous O2 tension but did not enhance vasoconstriction to glibenclamide. Despite an increase in O2‐extraction to ~90% during combined NLA + 8PT + glibenclamide, exercise‐induced hyperemia was maintained. Thus, KATP 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