Ouabain injected into the hypothalamus elicits pressor responses in anaesthetized rats: a mapping study

Cardiac glycosides are known to have a narrow therapeutic index, due in part to their effects on the brain. Injections of cardiac glycosides into the ventricles of the brain elicit activation of the autonomic nervous system, and may even elicit cardiac arrhythmias. However, the specific brain regions responsible for such action are unknown. The hypothalamus receives chemo- and baro-receptive innervation from the cardiovascular system. In turn, there are both direct and indirect effector pathways from the hypothalamus accessing the sympathetic preganglionic and parasympathetic ganglia regions. This suggests that the hypothalamus may be a prime candidate for the central toxic effects of cardiac glycosides. The purpose of this experiment was to map the rostral diencephalon to determine sites at which injections of a low dose of the cardiac glycoside, ouabain, resulted in altered cardiovascular responses in the anaesthetized rat. Microinjections of 20 ng of ouabain in 200 nl were made into sites throughout the rostral diencephalon of urethane (1.2 g/kg) anaesthetized rats while monitoring heart rate and blood pressure. Injections into the nucleus medianus, paraventricular, anterior and posterior hypothalamic nuclei produced increases in pressure of from 5 to 25 mmHg. These data suggest that part of the toxicity resulting from the cardiac glycoside administration may be due to the direct action of the glycosides on these hypothalamic structures. The paraventricular region has the greatest sensitivity and may be a primary target due to its direct connections with the preganglionic sympathetic regions in the spinal cord.