Pharmacological profile of the clonidine-induced inhibition of vasodepressor sensory outflow in pithed rats: correlation with alpha(2A/2C)-adrenoceptors

• Published in: British journal of pharmacology 2008-05, Vol.154 (1), p.51-59
• Main Authors: Villalón, C M, Albarrán-Juárez, J A, Lozano-Cuenca, J, Pertz, H H, Görnemann, T, Centurión, D
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Animals; Blood Pressure - drug effects; Blood Vessels - drug effects; Blood Vessels - innervation; Calcitonin Gene-Related Peptide - pharmacology; Clonidine - pharmacology; Decerebrate State - physiopathology; Electric Stimulation; Heart Rate - drug effects; Imidazoles - pharmacology; In Vitro Techniques; Isoindoles - pharmacology; Male; Neurons, Afferent - drug effects; Quinolizines - pharmacology; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-2 - drug effects; Receptors, Adrenergic, alpha-2 - physiology; Yohimbine - pharmacology
• ISSN: 0007-1188
• DOI: 10.1038/bjp.2008.49

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 alpha(2)-adrenoceptors in the inhibition of these vasodepressor responses. 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 microg kg(-1) min(-1)) or clonidine (3, 10 and 30 microg 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. The infusion of clonidine (10 microg kg(-1) min(-1)), as compared to those of methoxamine (15 or 30 microg kg(-1) min(-1)), inhibited the vasodepressor responses to electrical stimulation without affecting those to i.v. bolus injections of alpha-CGRP (0.1-1 microg kg(-1)). This inhibition by clonidine was: (i) antagonized by 300 microg kg(-1) rauwolscine (alpha(2A/2B/2C)), 300 and 1000 microg kg(-1) BRL44408 (alpha(2A)), or 10 and 30 microg kg(-1) MK912 (alpha(2C)); and (ii) unaffected by 1 ml kg(-1) saline, 100 microg kg(-1) BRL44408, 3000 and 10,000 microg kg(-1) imiloxan (alpha(2B)) or 3 microg kg(-1) MK912. The inhibition produced by 10 microg kg(-1) min(-1) clonidine on the vasodepressor (perivascular) sensory outflow in rats may be mainly mediated by prejunctional alpha(2A)/alpha(2C)-adrenoceptors.