α₂-Adrenoceptor-mediated inhibition of catecholamine release from the adrenal medulla of spontaneously hypertensive rats is preserved in the early stages of hypertension.

Publisher: Blackwell Country of Publication: England NLM ID: 101208422 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1742-7843 (Electronic) Linking ISSN: 17427835 NLM ISO Abbreviation: Basic Clin Pharmacol Toxicol Subsets: MEDLINE

Publication: <2005-> : Oxford : Blackwell
Original Publication: Copenhagen, Denmark : Oxford, UK : Nordic Pharmacological Society Distributed by Blackwell Munksgaard, 2004-

Adrenal Medulla/*metabolism ; Epinephrine/*metabolism ; Hypertension/*metabolism ; Norepinephrine/*metabolism ; Receptors, Adrenergic, alpha-2/*metabolism; Adrenal Medulla/drug effects ; Animals ; Dimethylphenylpiperazinium Iodide/pharmacology ; Hypertension/pathology ; Male ; Medetomidine/pharmacology ; Nicotinic Antagonists/pharmacology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Receptors, Adrenergic, alpha-2/drug effects

In this study, we evaluated the effect of α(2) -adrenoceptor activation on catecholamine release from the adrenal medulla of pre-hypertensive (6-week-old) and hypertensive (16-week-old) spontaneously hypertensive rats (SHR) and of age-matched normotensive control Wistar Kyoto (WKY) rats. Catecholamine overflow from isolated adrenal medullae was evoked by the nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) in the absence and presence of the α(2) -adrenoceptor agonist medetomidine (MED). The spontaneous outflow of adrenaline was similar between age-matched SHR and WKY rats. However, the spontaneous outflow of noradrenaline was significantly lower in SHR compared with age-matched WKY rats. DMPP (0.1-3 mM) increased the outflow of noradrenaline and adrenaline in a concentration-dependent manner. The E(max) values for adrenaline overflow were similar between strains, but the E(max) values for noradrenaline overflow were significantly lower in SHR. The EC(50) values for noradrenaline and adrenaline overflow were significantly higher in SHR compared with age-matched WKY rats. MED (0.1-300 nM) reduced the DMPP-evoked overflow (DMPP 500 μM) of noradrenaline and adrenaline in a concentration-dependent manner and was capable of totally inhibiting this effect. The inhibitory action of MED was similar between age-matched SHR and WKY rats. In the adrenals, the α(2A)- and α(2B)-adrenoceptor subtypes had the highest mRNA expression levels; the α(2C)-adrenoceptor subtype had the lowest mRNA expression levels. The mRNA levels for the three subtypes were similar between strains. In conclusion, in SHR during the development of hypertension, adrenal α(2) -adrenoceptor inhibitory function is conserved, accompanied by reduced noradrenaline release and unchanged adrenaline release.
(© 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.)

0 (Nicotinic Antagonists)
0 (Receptors, Adrenergic, alpha-2)
54-77-3 (Dimethylphenylpiperazinium Iodide)
MR15E85MQM (Medetomidine)
X4W3ENH1CV (Norepinephrine)
YKH834O4BH (Epinephrine)

Date Created: 20110427 Date Completed: 20120112 Latest Revision: 20131121

20250114

10.1111/j.1742-7843.2011.00712.x

21518261