G A Head1, S L Burke. 1. Neuropharmacology Laboratory, Baker Medical Research Institute, Melbourne, Australia. Geoff.Head@baker.edu.au
Abstract
OBJECTIVE: To determine the influence of imidazoline receptors and alpha2-adrenoceptors in the rostral ventrolateral medulla (RVLM) on the renal sympathetic baroreflex. METHODS: The effects of rilmenidine (4 nmol) and alpha-methylnoradrenaline (alpha-MNA, 80 nmol) micro-injected into the RVLM of urethane-anaesthetized rabbits previously implanted with renal nerve recording electrodes were examined before and after micro-injection of the imidazoline receptor/alpha2-adrenoceptor antagonist idazoxan and the alpha2-adrenoceptor antagonist 2-methoxyidazoxan (2-MI). RESULTS: Rilmenidine and alpha-MNA both lowered mean arterial pressure (MAP) by 28% and renal sympathetic nerve activity (RSNA) by 35%, and reduced RSNA upper plateaus and ranges by 30-70%. Rilmenidine decreased both sympathetic burst frequency and amplitude while alpha-MNA reduced amplitude only. Rilmenidine shifted the RSNA baroreflex curve to the left while alpha-MNA shifted the curve to the right Idazoxan (13 nmol) reversed the hypotension and all RSNA effects of rilmenidine, while 2-MI (4 nmol) increased MAP 18% above the control and also reversed all RSNA parameters. By contrast, 2-MI reversed the alpha-MNA-induced hypotension and partially restored RSNA and the upper plateau of the RSNA baroreflex curve. Idazoxan treatment only partially reversed the hypotension after alpha-MNA and had no effect on any of the baroreflex curves. CONCLUSION: Both alpha-MNA and rilmenidine injected into the RVLM of rabbits produce renal sympathetic inhibition, but differences in the location of the baroreflex curve and the pattern of effects on burst amplitude and frequency suggest different mechanisms of action. The effects of idazoxan suggest that rilmenidine acts via imidazoline receptors. Since 2-MI reversed the actions of alpha-MNA and also rilmenidine, this suggests that alpha2-adrenoceptor hypotension can be produced in the rabbit RVLM and that rilmenidine may activate alpha2-adrenoceptors, possibly as a result of activating imidazoline receptors.
OBJECTIVE: To determine the influence of imidazoline receptors and alpha2-adrenoceptors in the rostral ventrolateral medulla (RVLM) on the renal sympathetic baroreflex. METHODS: The effects of rilmenidine (4 nmol) and alpha-methylnoradrenaline (alpha-MNA, 80 nmol) micro-injected into the RVLM of urethane-anaesthetized rabbits previously implanted with renal nerve recording electrodes were examined before and after micro-injection of the imidazoline receptor/alpha2-adrenoceptor antagonist idazoxan and the alpha2-adrenoceptor antagonist 2-methoxyidazoxan (2-MI). RESULTS:Rilmenidine and alpha-MNA both lowered mean arterial pressure (MAP) by 28% and renal sympathetic nerve activity (RSNA) by 35%, and reduced RSNA upper plateaus and ranges by 30-70%. Rilmenidine decreased both sympathetic burst frequency and amplitude while alpha-MNA reduced amplitude only. Rilmenidine shifted the RSNA baroreflex curve to the left while alpha-MNA shifted the curve to the right Idazoxan (13 nmol) reversed the hypotension and all RSNA effects of rilmenidine, while 2-MI (4 nmol) increased MAP 18% above the control and also reversed all RSNA parameters. By contrast, 2-MI reversed the alpha-MNA-induced hypotension and partially restored RSNA and the upper plateau of the RSNA baroreflex curve. Idazoxan treatment only partially reversed the hypotension after alpha-MNA and had no effect on any of the baroreflex curves. CONCLUSION: Both alpha-MNA and rilmenidine injected into the RVLM of rabbits produce renal sympathetic inhibition, but differences in the location of the baroreflex curve and the pattern of effects on burst amplitude and frequency suggest different mechanisms of action. The effects of idazoxan suggest that rilmenidine acts via imidazoline receptors. Since 2-MI reversed the actions of alpha-MNA and also rilmenidine, this suggests that alpha2-adrenoceptor hypotension can be produced in the rabbit RVLM and that rilmenidine may activate alpha2-adrenoceptors, possibly as a result of activating imidazoline receptors.