Research Paper
Subject Category: Cardiovascular and pulmonary pharmacology
British Journal of Pharmacology (2008) 154, 51–59; doi:10.1038/bjp.2008.49; published online 25 February 2008
Pharmacological profile of the clonidine-induced inhibition of vasodepressor sensory outflow in pithed rats: correlation with 
2A/2C-adrenoceptors
C M Villalón1, J A Albarrán-Juárez1, J Lozano-Cuenca1, H H Pertz2, T Görnemann2 and D Centurión1
- 1Departamento de Farmacobiología, Cinvestav—Coapa, Tlalpan, México D.F., México
- 2Institut für Pharmazie, Freie Universität Berlin, Berlin (Dahlem), Germany
Correspondence: Professor CM Villalón, Departamento de Farmacobiología, Cinvestav-Coapa, Calzada de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, Mexico D.F 14330, Mexico. E-mail; cvillalon@cinvestav.mx
Received 9 November 2007; Revised 15 January 2008; Accepted 21 January 2008; Published online 25 February 2008.
Abstract
Background and purpose:
Resistance blood vessels are innervated by sympathetic and primary sensory nerves, which modulate vascular tone through the release of noradrenaline and calcitonin gene-related peptide (CGRP), respectively. Moreover, electrical stimulation of the perivascular sensory outflow in pithed rats results in vasodepressor responses which are mainly mediated by CGRP release. The present study has investigated the role of 
2-adrenoceptors in the inhibition of these vasodepressor responses.
Experimental approach:
144 pithed male Wistar rats were pretreated with hexamethonium (2 mg kg-
1 min-
1) followed by i.v. continuous infusions of either methoxamine (15 and 30 
g kg-
1 min-
1) or clonidine (3, 10 and 30 g kg-
1 min-
1). Under these conditions, electrical stimulation (0.56–5.6 Hz; 50 V and 2 ms) of the spinal cord (T9–T12) resulted in frequency-dependent decreases in diastolic blood pressure.
Key results:
The infusion of clonidine (10 g kg-
1 min-
1), as compared to those of methoxamine (15 or 30 g kg-
1 min-
1), inhibited the vasodepressor responses to electrical stimulation without affecting those to i.v. bolus injections of -CGRP (0.1–1 g kg-
1). This inhibition by clonidine was: (i) antagonized by 300 g kg-
1 rauwolscine (2A/2B/2C), 300 and 1000 g kg-
1 BRL44408 (2A), or 10 and 30 g kg-
1 MK912 (2C); and (ii) unaffected by 1 ml kg-
1 saline, 100 g kg-
1 BRL44408, 3000 and 10000 g kg-
1 imiloxan (2B) or 3 g kg-
1 MK912.
Conclusions and implications:
The inhibition produced by 10 g kg-
1 min-
1 clonidine on the vasodepressor (perivascular) sensory outflow in rats may be mainly mediated by prejunctional 2A/2C-adrenoceptors.
Keywords:
2-adrenoceptors, BRL44408, -CGRP, imiloxan, MK912, pithed rat, sensory nerves, vasodilatation
Abbreviations:
BRL44408, (2-[ 2H-(1-methyl-1,3-dihydroisoindole)methyl] -4,5-dihydroimidazole maleate; CGRP, calcitonin gene-related peptide; KO, knockout; MK912, (2S,12bs)1',3' dimethylspiro(1,3,4,5',6,6',7,12b-octahydro-2H-benzo[ b] furo [ 2,3-a] quinazoline)-2,4'-pyrimidin-2'one hydrochloride; NANC, non-adrenergic, non-cholinergic
