Neurons and receptors in the rostroventrolateral medulla mediating the antihypertensive actions of drugs acting at imidazoline receptors.

A group of clinically useful antihypertensive agents, including clonidine, moxonidine, and rilmenidine, are all ligands at alpha(2)-adrenergic and imidazoline (I-) receptors, the latter principally of the I1-subclass. These agents all lower blood pressure by reducing the activity of tonically active sympathoexcitatory reticulospinal neurons of the C1 area of the rostroventrolateral medulla (RVL). They tonically excite preganglionic sympathetic neurons in the spinal cord by release of L-glutamate and mediate most reflexes influencing blood pressure. The RVL contains alpha(2)-adrenergic and I1-receptors, and there is evidence to suggest that both receptors may participate in the hypotensive actions of the drugs. However, because only activation of the alpha(2)-adrenergic receptors appears responsible for somnolence, the imidazoline-receptor agonists moxonidine and rilmenidine, both relatively selective for I-receptors, may have superior clinical utility in antihypertensive therapy, since they are sympatholytic and also suppress the generation of angiotensin II.