Key result
In rats with acute renal failure, ethanol elicited dose-related decreases in blood pressure and increases in heart rate, mediated by central I1-sites and downstream ERK/p38 MAPK signalling.
The hypotensive effect of ethanol in a rat model of acute renal failure is mediated by central sympathoinhibitory pathways involving I1-sites and downstream ERK/p38 MAPK signalling.
Ethanol effects in this rat model should not guide clinical practice; leaves open translational relevance of central I1 and MAPK pathways.
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.
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El‐Mas et al. (2009) studied Acute renal failure (ARF). Ethanol was evaluated on Blood pressure (BP) and heart rate (HR) changes. In rats with acute renal failure, ethanol elicited dose-related decreases in blood pressure and increases in heart rate, mediated by central I1-sites and downstream ERK/p38 MAPK signalling.
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