Effects of adenosine and two stable adenosine analogues on blood pressure, heart rate and colonic temperature in the rat

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Abstract
Adenosine exerts effects via receptors of the A1‐ and A2‐subtype. L‐phenylisopropyl adenosine (L‐PIA) is more potent than N‐5′‐ethylcarboxamido adenosine (NECA) at the A1,‐subtype receptor whereas the potency order is reversed at the A2‐subtype receptor. Adenosine analogues have been shown to decrease blood pressure and heart rate and to induce a marked hypothermia. In the present series of experiments adenosine, L‐PIA and NECA were given i.p. or i.v. to rats, and blood pressure, ECG and colonic temperature were recorded. The NECA was the most potent of the compounds in reducing blood pressure (EC502 μkg‐1i.v.), followed by L‐PIA (EC50approximately 30 μ kg‐1i.v.) and adenosine (EC50approximately 300 μ kg‐1i.v.). In contrast, L‐PIA and NECA were equally active in reducing heart rate (EC50approximately 6 μ kg‐1i.v.) and considerably more potent than adenosine (EC50approximately 300 μ kg‐1i.v.). It is suggested that simultaneous measurement of blood pressure and heart rate could be a simplein vivomodel for comparison of A1‐ and A2‐receptor subtype mediated effects. Colonic temperature was markedly reduced after i.p. administration of the adenosine analogues. Thus, 100 μg NECA kg‐1reduced colonic temperature from 37.8 to 26 d̀C. A 5 d̀C temperature drop was obtained by 10 μg kg‐1NECA, by 200 μg kg‐1L‐PIA and by 200 mg kg‐1adenosine. The fall in colonic temperature was associated with a loss of muscular activity, as determined by needle electrodes or by palpation, indicating an inhibition of shivering. The fact that the agonist potency and the potency ratio were similar for the hypotensive and hypothermic effect could indicate that the fall in body temperature is dependent upon a peripheral vasodilatation. In addition there was an inhibition of shivering. The results are compatible with the opinion that adenosine analogues cause hypothermia largely because of peripheral effects, but a central inhibition of compensatory mechanisms, either at a spinal level or at the level of the hypothalamic temperature centre is probable.