Adenosine-mediated hypotension in in vivo guinea-pig: receptors involved and role of NO

1 Adenosine produced a biphasic lowering of the mean BP with a drastic brad ycardic effect at the highest doses. The first phase hypotensive response w as significantly reduced by the nitric oxide (NO) synthase inhibitor L-NAME . 2 The A(2a)/A(2b) agonist NECA produced hypotensive and bradycardic respons es similar to those elicited by adenosine, which were not significantly mod ified by the A(2b) antagonist enprofylline. 3 The A(2a) agonist CGS 21680 did not significantly influence basal HR whil e induced a hypotensive response antagonized by the A(2a) selective antagon ist ZM 241385, and reduced by both L-NAME and the guanylate cyclase inhibit or methylene blue. 4 The A(1) agonist R-PIA showed a dose-dependent decrease in BP with a dras tic decrease in HR at the highest doses. The Ai selective antagonist DPCPX significantly reduced the bradycardic activity and also the hypotensive res ponses obtained with the lowest doses while it increased those obtained wit h the highest ones. 5 The A(1)/A(3) agonist APNEA, in the presence of the xanthinic non-selecti ve antagonist 8-pSPT, maintained a significant hypotensive, but not bradyca rdic, activity, not abolished by the histamine antagonist diphenhydramine. 6 The selective A(3) agonist IB-MECA revealed a weak hypotensive and bradyc ardic effect, but only at the highest doses. 7 In conclusion, in the systemic cardiovascular response to adenosine two m ajor components may be relevant: an A(2a) and NO-mediated hypotension, and a bradycardic effect with a consequent hypotension, via atypical A(1) recep tors. Finally, an 8-pSPT-resistant hypotensive response not attributable to A(3) receptor-stimulation or to release of histamine by mastocytes or othe r immune cells was observed.