Abstract:
BACKGROUND AND PURPOSE:This study investigated the role of central sympathetic activity and related mitogen-activated protein kinase (MAPK) signalling in the cardiovascular effects of ethanol in a model of acute renal failure (ARF). EXPERIMENTAL APPROACH:The effects of pharmacological interventions that inhibit peripheral or central sympathetic activity or MAPK on the cardiovascular actions of ethanol in rats with ARF induced by glycerol were evaluated. KEY RESULTS:Glycerol (50%, 10 mL.kg(-1), i.m.) caused progressive increases and decreases in blood pressure (BP) and heart rate (HR) respectively. Subsequent i.v. ethanol (0.25 or 1 g.kg(-1)) elicited dose-related changes in BP (decreases) and HR (increases). These effects were replicated after intracisternal (i.c.) administration of ethanol. Blockade of nicotinic cholinoceptors (nAChR, hexamethonium, 20 mg.kg(-1)) or alpha(1)-adrenoceptors (prazosin, 1 mg.kg(-1)) attenuated cardiovascular effects of ethanol. Ethanol hypotension was also attenuated after the centrally acting sympatholytic drug moxonidine (selective I(1)-site agonist, 100 microg.kg(-1) i.v.), but not guanabenz (selective alpha(2)-receptor agonist, 30 microg.kg(-1), i.v.), suggesting involvement of central circuits of I(1) sites in ethanol-evoked hypotension. Selective blockade I(1) sites (efaroxan) but not alpha(2) (yohimbine) adrenoceptors abolished the hypotensive response to ethanol. Intracisternal administration of PD98059 or SB203580, inhibitors of extracellular signal-regulated kinase (ERK 1/2) and p38 MAPK, respectively, reduced the hypotensive action of moxonidine or ethanol. When used simultaneously, the two MAPK inhibitors produced additive attenuation of ethanol hypotension. CONCLUSIONS AND IMPLICATIONS:Sympathoinhibitory pathways of central I(1)-sites and downstream ERK/p38 MAPK signalling were involved in the hypotensive action of ethanol in ARF.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
El-Mas MM,El-Gowelli HM,Ghazal AR,Harraz OF,Mohy El-Din MMdoi
10.1111/j.1476-5381.2009.00444.xsubject
Has Abstractpub_date
2009-11-01 00:00:00pages
1629-40issue
6eissn
0007-1188issn
1476-5381pii
BPH444journal_volume
158pub_type
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