Ventrolateral medullary pressor area: site of hypotensive and sympatho-inhibitory effects of (±)8-OH-DPAT in anaesthetized dogs

Abstract

Injections of 8-OH-DPAT (0.1–6 μg/kg) into the vertebral artery or into the cisterna magna (5 μg/kg) produced a dose-dependent decrease in blood pressure, heart rate and renal sympathetic nerve activity in intact anaesthetized dogs and baroreceptor-denervated dogs. 8-OH-DPAT reduced the renal sympathetic nerve activity without changing the blood pressure or heart rate in catecholamine-depleted animals. Methiothepin (0.2 mg/kg) injected into the vertebral artery reduced the blood pressure without changing the heart rate or renal sympathetic nerve activity in baroreceptor-denervated dogs. The pressor response to i.v. phenylephrine was largely attenuated. Subsequent administration of 8-OH-DPAT (3 μg/kg) into the vertebral artery failed to alter the sympathetic discharge. Methiothepin (0.2 mg/kg) injected into the vertebral artery reversed the sympatho-inhibitory effect of 8-OH-DPAT (3 μg/kg) injected by the same route without changing the blood pressure. (±)Pindolol (0.2 mg/kg) injected into the vertebral artery of baroreceptor-denervated dogs reduced the blood pressure and heart rate without changing renal sympathetic activity. Subsequent administration of 8-OH-DPAT (3 μg/kg) failed to alter the sympathetic discharge. Bilateral microinjection of 8-OH-DPAT (1 μg) into the nucleus tractus solitarii or into the medullary raphe nuclei failed to alter the blood pressure, heart rate or renal sympathetic activity. In contrast, bilateral microinjections of 8-OH-DPAT into the ventrolateral pressor area (VLPA) (0.2 μg) produced a marked decrease in blood pressure, heart rate and renal sympathetic nerve activity. These effects were prevented or reversed by microinjections of methiothepin (10 μg) at the same sites. These results indicate that the central sympatho-inhibitory effects of 8-OH-DPAT were due to the stimulation of 5-HT 1A receptors located in the ventrolateral pressor area. 5-HT autoreceptors did not seem to be involved.