Intracerebroventricular injections of endothelin increase arterial pressure in conscious rats

We investigated the possible effects of endothelin (ET) on the central regulation of arterial pressure by injecting ET intracerebroventricularly (ICV) into conscious rats. ICV injections of ET caused dose-dependent elevation of arterial pressure and increase of heart rate. The first reaction was abolished by bunazosin, an alpha 1-adrenergic blocker, injected intravenously. However, the increase in arterial pressure and heart rate caused the rats, injected with ET ICV, to roll to the left on their long axis for 20-30 min, followed by prolonged sedation. Furthermore, the pressor responses and tachycardia were significantly attenuated by the ICV pretreatment with nicardipine, a calcium channel blocker, and nicorandil, a nitrate derivative, respectively. These results suggest that ET may elevate the intracellular Ca2+ concentration ([Ca2+]i) of sympathetic nerve activity regulatory neurons of the brain, leading to an accelerated outflow of sympathetic nerve activity and cause the elevation of arterial pressure.