The role of adenosine in functional hyperaemia in the coronary circulation of anaesthetized dogs.

Abstract

1. The aim of this investigation was to determine the contribution of adenosine to coronary active hyperaemia in the dog denervated heart by using adenosine deaminase. 2. Beagles were anaesthetized with thiopentone sodium (500 mg, i.v.) and chloralose (100 mg kg-', i.v.) and artificially ventilated. The hearts were denervated by bilateral cervical vagotomy and cardiac sympathectomy. Blood samples were collected from the coronary sinus via a cannula passed through the right external jugular vein. The anterior descending or circumflex branch of the left coronary artery was cannulated and perfused with blood from the left subclavian artery under systemic blood pressure through an electromagnetic flow probe and a perfusion circuit. The heart was paced (3 V, 0 2 ms and a suitable frequency) via two electrodes attached to the right atrium from 109 + 7-3 to 170 + 9 8 beats min-' (means + S.E.M.) for 3-4 min, first during an infusion of the solvent, and then during an infusion of a solution of adenosine deaminase (5 U kg-' min-') into the circuit. 3. In seventeen tests in eight dogs, infusion of adenosine deaminase did not cause a significant change in the basal coronary blood flow nor in the immediate increase (within 10 s) in blood flow induced by pacing the heart from its basal rate to 170 beats min-'.However, adenosine deaminase did cause a significant attenuation by 58 + 5 2 % (P < 0 05) of the increase in coronary blood flow induced at 3-4 min of pacing from 31 + 4-6 to 43 + 5 8 ml min-' (100 g cardiac tissue)-'. Concomitantly, the pacing-induced increase in coronary vascular conductance (from 0-41 + 0-08 to 0 54 + 0-12 ml min-' (100 g)' mmHg-') was reduced by 75 + 6-6% (P < 0 02) and the increase in myocardial 02 consumption (from 13 + 3 5 to 21 + 4 2 ml min-' (100 g)-) was reduced by 50 + 12% (P < 0 05) but without significant changes in oxygen extraction or myocardial contractility. 4. The results show that although adenosine is unlikely to play a significant role in the regulation of the basal coronary blood flow, it can play a major role in the coronary active (functional) hyperaemia induced by atrial pacing to a high rate in the denervated heart of anaesthetized dogs.

Mediators of coronary reactive hyperaemia in isolated mouse heart

“…A greater contribution of A 2 ARs to basal tone in mice could reflect increased importance of adenosine as metabolic rate rises. This is consistent with data on coronary regulation during periods of enhanced metabolic rate in larger species (Kang et al ., 1990; Karim & Goonewardene, 1996; Ishibashi et al ., 1998).…”

oxLDLspecifically impairs endothelium-dependent, NO-mediated dilation of coronary arterioles

“…It is well documented that coronary blood flow is significantly influenced by interstitial levels of adenosine (3,30,55). Direct observation of coronary blood vessels in vivo (22) or in vitro (31) indicates that adenosine preferentially dilates microvessels Ͻ150 µm in diameter.…”

Integrated modulation of sympathetic tone in the microcirculation by oxygen, adenosine, and nitric oxide

“…Later, Proctor (1986) reported that these same treatments significantly reduced, but did not eliminate, the level of absorptive hyperemia in the rat intestine. Similarly, other investigators have reported a role for adenosine in the mediation of active hyperemia in the cat soleus and gracilis muscle, the dog gracilis muscle, and in the dog heart (Schwartz and McKenzie, 1990; Goonewardene and Karim, 1991;Karim and Goonewardene, 1996).…”