REGULATION OF ADENOSINE RECEPTOR FUNCTION BY THEOPHYLLINE IN RAT AORTA

The effect of chronic theophylline treatment on adenosine receptor fun ction was investigated in rat aorta. Male Wistar rats were fed theophy lline (1 g/L) in drinking water for 30 days. The relaxation-response c urves to various adenosine receptor agonists, nonselective 5'-N-ethylc arboxamidoadenosine (NECA), A(2)-, selective 2-phenylaminoadenosine (C V-1808), and A(1)- selective N-6-(2-endo-norbornyl) adenosine (S-ENBA) were generated in aortic rings from control and treated rats. The rel axation curves to both NECA and CV-1808 (10(-9)-10(-4) M) were signifi cantly attenuated in treated rings (endothelium intact) as compared wi th control. S-ENBA showed a contraction at a lower concentration (10(- 10)-10(-6) M) in treated rings as compared with control. Because S-ENB A is highly A, selective, it produced relaxation only at 10(-4) M. Sim ilar to that of adenosine analogues, the isoproterenol (ISO 10(-9)-10( -5) M)) concentration-relaxation curve was shifted to the right in tre ated rats. Endothelium removal of the vascular rings decreased the mag nitude of relaxation to these agonists and eliminated the difference i n relaxation between control and treated groups. The relaxation to ace tylcholine (ACh), an endothelium-dependent relaxing agent, was also at tenuated in the theophylline-treated group. The relaxation responses t o forskolin (10(-11)-10(-8) M)) and sodium nitroprusside (SNP 10(-10)- 10(-7) M) were unaltered in treated rats. These data suggest an endoth elium-dependent downregulation of adenosine receptor function together with beta-adrenoceptor after chronic theophylline treatment.