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Pharmacological profile of the clonidine‐induced inhibition of vasodepressor sensory outflow in pithed rats: correlation with α 2A/2C ‐adrenoceptors
Author(s) -
Villalón C M,
AlbarránJuárez J A,
LozanoCuenca J,
Pertz H H,
Görnemann T,
Centurión D
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/bjp.2008.49
Subject(s) - methoxamine , clonidine , endocrinology , stimulation , medicine , hexamethonium , calcitonin gene related peptide , blood pressure , chemistry , saline , bolus (digestion) , rauwolscine , antagonist , neuropeptide , agonist , receptor , yohimbine
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 α 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 μg kg −1 min −1 ) or clonidine (3, 10 and 30 μg kg −1 min −1 ). Under these conditions, electrical stimulation (0.56–5.6 Hz; 50 V and 2 ms) of the spinal cord (T 9 –T 12 ) resulted in frequency‐dependent decreases in diastolic blood pressure. Key results: The infusion of clonidine (10 μg kg −1 min −1 ), as compared to those of methoxamine (15 or 30 μg kg −1 min −1 ), inhibited the vasodepressor responses to electrical stimulation without affecting those to i.v. bolus injections of α‐CGRP (0.1–1 μg kg −1 ). This inhibition by clonidine was: (i) antagonized by 300 μg kg −1 rauwolscine (α 2A/2B/2C ), 300 and 1000 μg kg −1 BRL44408 (α 2A ), or 10 and 30 μg kg −1 MK912 (α 2C ); and (ii) unaffected by 1 ml kg −1 saline, 100 μg kg −1 BRL44408, 3000 and 10000 μg kg −1 imiloxan (α 2B ) or 3 μg kg −1 MK912. Conclusions and implications: The inhibition produced by 10 μg kg −1 min −1 clonidine on the vasodepressor (perivascular) sensory outflow in rats may be mainly mediated by prejunctional α 2A /α 2C ‐adrenoceptors.