Central cardiovascular effects of a noncatecholamine endogenous ligand for clonidine receptors

Cats and rats anaesthetized with pentobarbital were used to study the central cardiovascular effects of the clonidine displacing substance (CDS). The potential influence of centrally applied CDS on the cardiovascular effects of clonidine was also investigated in both species. CDS is a brain substance which is not a catecholamine (CA) and which displaces completely the binding of tritiated clonidine to brain membranes. It was observed that direct application of CDS unilaterally to the nucleus reticularis lateralis (NRL), a privileged site of action for clonidine in the cat, increases markedly the mean arterial pressure (MAP) and does not affect the heart rate (HR). CDS also causes hypertension when infused into the left vertebral artery in the cat. When MAP reverted to baseline, the hypotensive effect of clonidine given by the same route is significantly prevented. In rats, the intracisternal administration of CDS increased MAP without affecting HR. Here also, the CDS pretreatment antagonized the hypotensive effect of i.v. clonidine as compared with control animals. It is concluded that CDS is an endogenous non-catecholamine ligand for receptors involved in the hypotensive effect of clonidine. This substance interferes with clonidine on these receptors. It is a candidate as a neuromodulator or a neurotransmitter involved in the blood pressure regulation at least in the NRL region.