A circulating substance cross-reacting with antiimidazoline antibodies. Detection in serum in relation to essential hypertension.

Abstract

It has been shown in various mammal species that clonidine, a well known 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 and insensitive to catecholamines have been detected in rat and bovine, as well as human brains. An endogenous ligand, other than catecholamines, should exist for these IRs. Such a ligand could play a role in the pathophysiology of human essential hypertension. Therefore, we developed 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 serum. 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 essential hypertensive patients' sera proved higher in -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 hyper-

Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine‐mediated blood pressure reaction

“…The use of SHR in our study was based on experience gained with this model from earlier studies; clonidine and agmatine were both shown to influence blood pressure and/or catecholamine overflow in pithed SHR (Häuser & Dominiak, 1995; Häuser et al ., 1995). Furthermore, CDS was shown to be increased in plasma of hypertensive patients and was positively correlated with blood pressure (Dontenwill et al ., 1993). This suggests that agmatine may also have a special impact in hypertension, which justifies the use of SHR.…”