Fostering orphan receptors: an indispensable role for integrative, in vivo haemodynamic studies

The assessment of cardiovascular effects of well-recognised ligands for their known receptors can produce misleading results if measurements are restricted to blood pressure and heart rate in anaesthetised animals. Therefore, we propose that the most reliable delineation of any role for a particular ligand-receptor system in cardiovascular regulation can only be achieved by determination of the detailed haemodynamic effects of manipulating the system in vivo, in the absence of anaesthesia. This approach is powerful because, firstly, differences between in vitro and in vivo effects, possibly attributable to disparities between receptor genotype and receptor phenotype, are highlighted; and secondly, regional heterogeneity of cardiovascular effects, possibly in the absence of changes in systemic arterial blood pressure, can be detected.