Central effect of endothelin on blood pressure in conscious rats

This study was conducted to investigate the effect of intracerebroventricular administration of endothelin (EDT), a novel potent vasoconstricting peptide, on blood pressure in conscious rats. The lateral cerebral ventricle of male Wistar rats was cannulated, and the femoral artery was also cannulated to measure the mean arterial blood pressure (MABP) and heart rate (HR). EDT dissolved in 10 microliters of artificial cerebrospinal fluid (ACSF) (8.25-66 pmol icv) provoked a dose-dependent increase in MABP. EDT also increased HR, although the effect of 66 pmol was variable. Intracerebroventricular ACSF did not provoke any effects on MABP and HR. Intracerebroventricular EDT also provoked contralateral rotational behavior. Pretreatment with 2 mg/kg iv phenoxybenzamine significantly suppressed the 16.5 pmol icv EDT-induced increase in MABP. Moreover, 16.5 pmol icv EDT markedly increased plasma epinephrine and norepinephrine concentration. These results indicate that EDT has a central pressor action, and the action might be mediated, at least in part, by catecholamine release to the periphery. EDT might play a role in the central control of blood pressure, although the physiological implications have not yet been determined.