AGE-RELATED CHARACTERIZATION OF ATRIAL ADENOSINE A(1) RECEPTOR ACTIVATION - DIRECT EFFECTS ON CHRONOTROPIC AND INOTROPIC FUNCTION IN THE FISCHER-344 RAT

Adenosine, an endogenously produced nucleoside, has direct negative ch ronotropic and inotropic effects on right and left atrial tissues, res pectively. Age-related differences in the effects of A(1) adenosine re ceptor activation on atrial rhythmic and contractile function were inv estigated in adult (6-8 months) and senescent (23-24 months) Fischer 3 44 (F344) rots. Senescent right atria (RA) were more sensitive to the negative chronotropic effects of R-phenylisopropyladenosine (R-PIA), a selective A(1) receptor agonist, than adult RA (EC(50):4.8 +/- 0.7 vs 10.8 +/- 1.5 mM). However, senescent left atria (LA) were 15.4% less responsive to the maximal negative inotropic effects of R-PIA than adu lt LA. R-PIA did not significantly change resting force from basal val ues in either age group, but 90% relaxation time was prolonged threefo ld in senescent LA compared with adults. Radioligand binding experimen ts with 1,3-[H-3]dipropyl-8-cyclopentylxanthine, a selective adenosine A(1) receptor antagonist, showed a 56% greater density (B-max) of ade nosine A(1) receptor in senescent than adult without differences in af finities (K-d). The increased sensitivity of senescent RA to the negat ive chronotropic effects of adenosine A(1) receptor stimulation sugges ts a role for adenosine in abnormal sinus node function that occurs mo re frequently with age. Adenosine A(1) receptor stimulation has more e ffect on relaxation than contraction in Senescent LA compared with LA from adult F344 rats. However, the increase irt density of adenosine A (1) receptors suggests a functional dissociation between the availabil ity of binding sires and receptor activation.