Adenylyl cyclase and soluble guanylyl cyclase activities were measured in cardiac and aortic tissue from transgenic hypertensive TGR(mREN2)27 and normotensive Sprague-Dawley rats. Cardiac basal and stimulated adenylyl cyclase activity was significantly lower in TGR(mREN2)27 than in Sprague-Dawley rats except after uncoupling of G-proteins by Mn2+-ions. Aortic cAMP formation did not differ between both strains, indicating that the disturbance of cardiac adenylyl cyclase activity was due to local rather than systemic factors. Vascular cGMP formation was significantly reduced in TGR(mREN2)27 aortae under basal conditions and after stimulation with sodium nitroprusside, indicating that there is a subsensitive vasodilating second messenger pathway in the transgenic strain.