Effects of clonidine on the reflex cardiovascular responses and release of substance P during muscle contraction

The effects of microdialyzing clonidine into the L-7 dorsal horn on the cardiovascular responses, renal sympathetic nerve activity (RSNA), and release of substance P (SP) evoked by static contraction of the triceps surae muscle were studied using anesthetized cats. A microdialysis probe was inserted into the spinal cord ipsilateral to the muscle being contracted or stretched. Contraction, evoked by stimulation of the distal ends of the cut L-7 and S-1 ventral roots for 1 minute, increased mean arterial pressure (MAP), heart rate (HR), and RSNA by 48±6 mm Hg, 18±2 beats per minute, and 66±5%, respectively. Passive stretch of the same muscle for 1 minute also increased MAP, HR, and RSNA by 51±6 mm Hg, 17±2 beats per minute, and 50±3%, respectively. Microdialysis of clonidine (380 μmol/L) blunted the contraction-evoked responses: MAP, HR, and RSNA increased by 19±4 mm Hg, 7±1 beats per minute, and 24±5%, respectively. The increases elicited by passive stretch were also attenuated (MAP, 22±4 mm Hg; HR, 6±1 beats per minute; and RSNA, 15±4%). This attenuation by clonidine was dose dependent (3.8 μmol/L, 38 μmol/L, 380 μmol/L, and 3.8 mmol/L). Preadministration of the α₂-adrenergic antagonist yohimbine (3 mmol/L) blocked the effect of clonidine (380 μmol/L) on the cardiovascular and RSNA responses to muscle contraction. Clonidine (380 μmol/L) did not alter the release of SP in the dorsal horn during contraction (before clonidine, 0.380±0.018 fmol/100 μL; after clonidine, 0.356±0.012 fmol/100 μL). These results demonstrate that stimulation of α₂-adrenergic receptors in the L-7 dorsal horn attenuates the cardiovascular responses and RSNA changes to static contraction and passive stretch. This attenuation by clonidine appears not to be mediated through presynaptic inhibition of SP release.