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 mu mol/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 mu mol/L, 38 mu mol/L, 380 mu mol/L, and 3.8 mmol/L). Preadministration of the alpha(2)-adrenergic antagonist yohimbine (3 mmol/L) blocked the effect of clonidine (380 mu mol/L) on the cardiovascular and RSNA responses to muscle contraction. Clonidine (380 mu mol/L) did not alter the release of SP in the dorsal horn during contraction (before clonidine, 0.380+/-0.018 fmol/100 mu L; after clonidine, 0.356+/-0.012 fmol/ 100 mu L). These results demonstrate that stimulation of alpha(2)-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.