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 mumol/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 mumol/L, 38 mumol/L, 380 mumol/L, and 3.8 mmol/L). Preadministration of the alpha 2-adrenergic antagonist yohimbine (3 mmol/L) blocked the effect of clonidine (380 mumol/L) on the cardiovascular and RSNA responses to muscle contraction. Clonidine (380 mumol/L) did not alter the release of SP in the dorsal horn during contraction (before clonidine, 0.380 +/- 0.018 fmol/100 microL; after clonidine, 0.356 +/- 0.012 fmol/100 microL).(ABSTRACT TRUNCATED AT 250 WORDS)
Ally
A
A
Harry S. Moss Heart Center, UT Southwestern Medical Center, Dallas 75235-9034.
Meintjes
A F
AF
Mitchell
J H
JH
Wilson
L B
LB
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D009119:Muscle Contraction; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000378:metabolism*; D013997:Time Factors
D013373:Substance P; D003000:Clonidine