A CIRCULATING SUBSTANCE CROSS-REACTING WITH ANTIIMIDAZOLINE ANTIBODIES - DETECTION IN SERUM IN RELATION TO ESSENTIAL-HYPERTENSION

It has been shown in various mammal species that clonidine, a well kno wn centrally acting hypotensive agent, acts through the activation of imidazoline receptors (IRs) in the nucleus reticularis lateralis (NRL) of the brainstem. Specific binding sites sensitive to imidazolines an d insensitive to catecholamines have been detected in rat and bovine, as well as human brains. An endogenous ligand, other than catecholamin es, should exist for these IRs. Such a ligand could play a role in the pathophysiology of human essential hypertension. Therefore, we develo ped two RIAs with polyclonal and monoclonal anticlonidine antibodies. These antibodies presented specificity spectra similar to that of the IRs: they bound imidazolines and not catecholamines at all. These RIAs were used to detect imidazoline-like immunoreactivity in the human se rum. Immunoreactive substance was measured in 26 normotensive subjects ' sera, and specificity of interaction between antibodies and sera was verified. None of the known endogenous substances tested so far were able to interact with the two antibodies. Immunoreactivity in 32 essen tial hypertensive patients' sera proved higher in approximately 30% of cases. Values of immunoreactivity positively correlated with the mean arterial pressure values. This study demonstrates the existence of an ''imidazoline-like'' immunoreactive substance in the human serum with high levels in some hypertensive patients.