Sympathoinhibitory effects of clonidine are transmitted by the caudal ventrolateral medulla in cats.
We examined mechanisms of the central sympathoinhibitory actions of systemically administered clonidine in anesthetized cats. To avoid influences of sympathetic chemo- and baroreflexes, the animals were deafferentated by cutting the carotid sinus and vagal nerves bilaterally. Intravenous (i.v.) injections of clonidine (25-250 nmol/kg) caused significant (50-90%) decreases in preganglionic sympathetic nerve activity (SNA) recorded from the white ramus of the third thoracic segment. Microinjections (500 nl) into the rostral ventrolateral medulla (RVLM) of clonidine at doses (50-500 pmol in 500 nl), which probably produced higher local concentrations than produced by systemic administration, caused only slight reductions of SNA and small decreases in arterial blood pressure (BP). Furthermore, sympathoinhibition and hypotension caused by intravenous clonidine was almost unaffected by prior microinjection of alpha2-receptor antagonist rauwolscine (500 pmol) into the RVLM. Microinjections of clonidine into the caudal ventrolateral medulla (CVLM), which provides important inhibitory input to the RVLM, had no significant effects. However, chemical lesions of the CVLM with kainate (5.0 nmol), effectively blocked the sympathoinhibitory effects of subsequently administered intravenous clonidine. The results suggest that the central sympathoinhibitory effects of therapeutically relevant doses of systemically administered clonidine may be primarily mediated by pathways that activate the CVLM rather than by direct actions within the RVLM.
Seller
H
H
I. Physiologisches Institut, University of Heidelberg, Germany.
Czachurski
J
J
Zanzinger
J
J
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D003000:Clonidine / Q000494:pharmacology*; D007262:Infusions, Intravenous; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013565:Sympatholytics / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D013565:Sympatholytics; D015016:Yohimbine; D003000:Clonidine