Effects of the adenylyl cyclase inhibitor SQ22536 on iloprost‐induced vasorelaxation and cyclic AMP elevation in isolated guinea‐pig aorta

The stable prostacyclin analogue, iloprost relaxes a variety of blood vessels and increases cyclic AMP, although the relationship between adenosine 3′ : 5′‐cyclic monophosphate (cyclic AMP) and vasorelaxation remains unclear. We therefore investigated the effect of the adenylyl cyclase inhibitor, 9‐(tetrahydro‐2‐furanyl)‐9H‐purin‐6‐amine (SQ22536) on iloprost‐mediated relaxation and cyclic AMP elevation in endothelium‐denuded aortic strips. Iloprost (1–1000 nM) caused a concentration‐dependent inhibition of phenylephrine (1–6 μM) contractions, the responses being unaffected by pre‐incubation with SQ22536 (100 μM) for 30 min. In other experiments 60 nM iloprost caused a 64% inhibition of phenylephrine contractions concomitant with a 3 fold rise in cyclic AMP. SQ22536 completely abolished the iloprost‐induced elevation in cyclic AMP while having no significant effect on relaxation. Our results therefore strongly suggest that cyclic AMP‐independent pathways are responsible for the vasorelaxant effects of iloprost in guinea‐pig aorta. British Journal of Pharmacology (1999) 126, 845–847; doi:10.1038/sj.bjp.0702383