Age-related changes in adenosine-mediated relaxation of coronary and aortic smooth muscle

We tested whether adenosine mediates nitric oxide (NO)-dependent and NO-ind ependent dilation in coronary and aortic smooth muscle and whether age sele ctively impairs NO-dependent adenosine relaxation. Responses to adenosine a nd the relatively nonselective analog 5'-N-ethylcarboxamidoadenosine (NECA) were studied in coronary vessels and aortas from immature (1-2 mo), mature (3-4 mo), and moderately aged (12-18 mo) Wistar and Sprague-Dawley rats. A denosine and NECA induced biphasic concentration-dependent coronary vasodil ation, with data supporting high-sensitivity (pEC(50) = 5.2-5.8) and low-se nsitivity (pEC(50) = 2.3-2.4) adenosine sites. Although sensitivity to aden osine and NECA was unaltered by age, response magnitude declined significan tly. Treatment with 50 muM N-G-nitro-L-arginine methyl ester (L-NAME) marke dly inhibited the high-sensitivity site, although response magnitude still declined with age. Aortic sensitivity to adenosine declined with age (pEC(5 0) = 4.7 +/- 0.2, 3.5 +/- 0.2, and 2.9 +/- 0.1 in immature, mature, and mod erately aged aortas, respectively), and the adenosine receptor transduction maximum also decreased (16.1 +/- 0.8, 12.9 +/- 0.7, and 9.6 +/- 0.7 mN/mm( 2) in immature, mature, and moderately aged aortas, respectively). L-NAME d ecreased aortic sensitivity to adenosine in immature and mature tissues but was ineffective in the moderately aged aorta. Data collectively indicate t hat 1) adenosine mediates NO-dependent and NO-independent coronary and aort ic relaxation, 2) maturation and aging reduce NO-independent and NO-depende nt adenosine responses, and 3) the age-related decline in aortic response a lso involves a reduction in the adenosine receptor transduction maximum.