Effect of adenosine and its stabile analogue 2-chloroadenosine on cerebrocortical microcirculation and NAD/NADH redox state

Abstract

In the present study, the effects of topically applied adenosine (ADO) and its stabile analogue 2-chloroadenosine (CADO) on cerebrocortical microcirculation and NAD/NADH redox state (oxidized/reduced nicotinamide adenine dinucleotide) were investigated. Vascular volume (CVV), mean transit time of blood flow (tm), blood flow (CBF), and NADH fluorescence of the cat brain cortex were measured through a cranial window with a microscope fluororeflectometer. The reference values of CVV, tm, and CBF, measured in the artificial cerebrospinal fluid (mock CSF) which superfused brain cortex, were regarded as 100%. Adenosine and 2-chloroadenosine, in the concentration range of 10(-6) - 10(-3) M, resulted in concentration-dependent increases in CBF and NAD reduction. 10(-5) M adenosine and 2-chloroadenosine increased CBF by 49.6 +/- 5.6% and 80.4 +/- 10.3%, respectively. At a pharmacologically high concentration (10(-3) M), ADO increased CBF by 164.6 +/- 13.5%, CADO by 333 +/- 44%. At the same time, 10(-3) M ADO and CADO shifted the cortical NAD/NADH redox state by 7.9 +/- 0.4% and 12.4 +/- 0.7%, respectively toward a more reduced state. Our results, concerning the vasodilator potency of adenosine and 2-chloroadenosine, accord with available data in the literature. However, the pronounced NAD reduction obtained with these adenosine nucleosides suggests that, besides an action on vascular adenosine receptors, some other changes, such as increased substrate mobilization and possibly cAMP production, may contribute to the vasodilator effect of adenosine and 2-chloroadenosine.