Adenosine A 1 receptors and vascular reactivity Y. Wang, 1,2 * J. N. Yang, 1 * A. Arner, 1 P. J. M. Boels 1 and B. B. Fredholm 1 1 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden 2 College of Pharmacy, Jilin University, Changchun, Jilin, China Received 2 November 2009, accepted 1 December 2009 Correspondence: B. B. Fredholm, Department of Physiology and Pharmacology, Karolinska Institutet, S 171 77 Stockholm, Sweden. E-mail: bertil.fredholm@ki.se * These authors contributed equally to this study. Abstract Aim: Blood pressure is higher in A 1 receptor knock-out (A 1 R)/)) mice than in wild type litter mates (A 1 R+/+) and we have examined if this could be related to altered vascular functions. Methods: Contraction of aortic rings and mesenteric arteries were exam- ined. To examine if the adenosine A 1 receptor-mediated contraction of aortic muscle was functionally important we examined pulse pressure (PP) and augmentation index (AIX) using a sensor that allows measurements of rapid pressure transients. Results: Contraction of aortic rings to phenylephrine and relaxation to acetylcholine were similar between genotypes. The non-selective adenosine receptor agonist N-ethyl carboxamido adenosine (NECA) enhanced the contractile response, and this was eliminated in aortas from A 1 R)/) mice. However, in mesenteric arteries no contractile response was seen and adenosine-mediated relaxation was identical between studied genotypes. A 2B adenosine receptors, rather than A 2A receptors, may be mainly responsible for the vasorelaxation induced by adenosine analogues in the examined mouse vessels. PP was higher in A 1 R)/) mice, but variability was unaltered. AIX was not different between genotypes, but the NECA-induced fall was larger in A 1 R)/) mice. Conclusions: The role of adenosine A 1 receptors in regulating vessel tone differs between blood vessels. Furthermore, contractile effects on isolated vessels cannot explain the blood pressure in A 1 knock-out mice. The A 1 receptor modulation of blood pressure is therefore mainly related to extra- vascular factors. Keywords aorta, blood pressure, knock-out, mesenteric artery, pulse pressure, vascular reactivity. There are four different receptors for adenosine: A 1 , A 2A ,A 2B and A 3 (Fredholm et al. 2001). Via its actions on A 1 receptors, endogenous adenosine is known to strongly influence renal function (Brown et al. 2001, Sun et al. 2001), the central nervous system (Fredholm et al. 2005) and intermediary metabolism (Dhalla et al. 2003, Johansson et al. 2007, 2008). The evidence for a cardiovascular role of A 1 receptors is more limited, although data on its role in the regulation of heart rate (Wu et al. 2001, Yang et al. 2007, 2009) and in the modulation of the consequences of a cardiac ischaemic insult (Headrick et al. 2003, Lankford et al. 2006, Morrison et al. 2006) are quite strong. Endogenous adenosine acting on A 1 receptors was reported to only minimally influence blood pressure and vascular reac- tivity based on experiments using different antagonists (e.g. Kuan et al. 1993). In later experiments using mice lacking the A 1 receptor (Johansson et al. 2001, Sun et al. 2001) results have been more ambiguous. In one of the two knock-out strains blood pressure was Acta Physiol 2010, 199, 211–220 Ó 2010 The Authors Journal compilation Ó 2010 Scandinavian Physiological Society, doi: 10.1111/j.1748-1716.2010.02093.x 211