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INTERSTITIAL ADENOSINE AND FUNCTION IN RAT HEART IN VIVO : EFFECTS OF ADRENALINE AND 8‐CYCLOPENTYL‐1,3‐DIMETHYLXANTHINE
Author(s) -
Headrick John P
Publication year - 1996
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1996.tb02746.x
Subject(s) - adenosine , medicine , heart rate , endocrinology , stimulation , bradycardia , chemistry , rate pressure product , basal (medicine) , blood pressure , insulin
SUMMARY 1. Left ventricular interstitial adenosine and cardiac function were studied in open chest rats during adrenaline stimulation and P 1 ‐purinoceptor antagonism with 8‐cyclopentyl‐1,3‐dimethylxanthine (8‐CPT). 2. Cardiac microdialysate adenosine concentration was 0.10±0.01 μmol/L ( n = 24) under basal conditions, giving an estimated interstitial adenosine concentration of 0.27 μmol/L. Stimulation with 3.2 and 8.0 μg/kg per min adrenaline increased the rate‐pressure product (heart rate X systolic blood pressure) by 72 and 157%, respectively, and increased dialysate adenosine to 0.26±0.04 and 0.65±0.11 μmol/L ( n = 12), respectively (interstitial concentrations of approximately 0.70 and 1.76 μmol/L). 3. Treatment with 60 μg/kg per min 8‐CPT did not alter basal adenosine concentrations, but potentiated elevations in dialysate adenosine during infusion of 3.2 and 8.0 μg/kg per min adrenaline to 0.54±0.10 and 1.30±0.22 μmol/L, respectively ( n = 12). Basal function and the response to 8.0 μg/kg per min adrenaline were unaltered by 8‐CPT, whereas elevations in heart rate and rate‐pressure product during stimulation with 3.2 μg/kg per min adrenaline were enhanced by 8‐CPT (by up to 30%). 4. Studies in isolated hearts confirmed the inhibitory potency of 8‐CPT at A 1 vs A 2 P 1 ‐purinoceptors (e.g. pK B of 7.7±0.2 and 6.4±0.1 for 5′‐ N ‐ethyl carboxamidoadenosine‐mediated bradycardia and vasodilatation, respectively; n = 6). Studies in intact animals verified effective A 1 blockade by 60 μg/kg per min 8‐CPT, but also revealed some inhibition of A 2 ‐mediated responses. 5. In conclusion, the data show that cardiac interstitial adenosine levels exist within a physiologically active range in vivo and increase dose‐dependently during graded adrenaline stimulation. Adenosine receptor antagonism enhances elevations in interstitial adenosine and modifies functional responses to moderate, but not high, doses of adrenaline. Whether 8‐CPT‐dependent elevations in interstitial adenosine are due to A 1 inhibition vs inhibition of A 2 ‐mediated vasodilatation requires further investigation.