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Interstitial Adenosine and Function in Rat Heart in Vivo: Effects of Adrenaline and 8-cyclopentyl-1,3-dimethylxanthine

Interstitial Adenosine and Function in Rat Heart in Vivo: Effects of Adrenaline and 8-cyclopentyl-1,3-dimethylxanthine

J P Headrick

Clin Exp Pharmacol Physiol. 1996 May;23(5):386-94.

PMID: 8713676

Abstract:

1. Left ventricular interstitial adenosine and cardiac function were studied in open chest rats during adrenaline stimulation and P1-purinoceptor antagonism with 8-cyclopentyl-1,3-dimethylxanthine (8-CPT). 2. Cardiac microdialysate adenosine concentration was 0.10 +/- 0.01 mumol/L (n = 24) under basal conditions, giving an estimated interstitial adenosine concentration of 0.27 mumol/L. Stimulation with 3.2 and 8.0 micrograms/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 mumol/L (n = 12), respectively (interstitial concentrations of approximately 0.70 and 1.76 mumol/L). 3. Treatment with 60 micrograms/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 micrograms/kg per min adrenaline to 0.54 +/- 0.10 and 1.30 +/- 0.22 mumol/L, respectively (n = 12). Basal function and the response to 8.0 micrograms/kg per min adrenaline were unaltered by 8-CPT, whereas elevations in heart rate and rate-pressure product during stimulation with 3.2 micrograms/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 A1 vs A2 P1-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 A1 blockade by 60 micrograms/kg per min 8-CPT, but also revealed some inhibition of A2-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 A1 inhibition vs inhibition of A2-mediated vasodilatation requires further investigation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP35873495	8-Cyclopentyl-1,3-dimethylxanthine		35873-49-5	Price

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