Characterization of the depressor effect of intrathecal endothelin in anesthetized rats

Intrathecal administration of 1-100 pmol endothelin-1 in urethan-anesthetized rats elicited a dose-dependent decrease in arterial pressure and a modest bradycardia. The depressor response was associated with a sustained hindquarters vasodilation and a modest transient mesenteric vasoconstriction, indicating disparate effects on regional vascular resistance. In contrast, renal sympathetic nerve activity was unaffected except at the highest dose of endothelin-1 (100 pmol). The depressor effect of intrathecal endothelin is unlikely to be due to spinal ischemia produced by vasoconstriction, since a much greater dose of endothelin was needed to produce an increase in spinal vascular resistance compared with the dose necessary to produce hindquarters vasodilation and the depressor effect. Unlike intravenous administration, intrathecal endothelin-1 and endothelin-3 produced indistinguishable effects on arterial pressure, heart rate, renal sympathetic nerve activity, spinal blood flow, and spinal vascular resistance, suggesting that the spinal neuronal endothelin receptors may be less selective than those in the blood vessels. The centrally mediated depressor effect and the selective regional hemodynamic actions of intrathecal endothelin suggest a role of spinal endothelin in regulating cardiovascular function.