Chronic ethanol attenuates centrally-mediated hypotension elicited via α2-adrenergic, but not I1-imidazoline, receptor activation in female rats

El‐Mas, Mahmoud M.; Abdel‐Rahman, Abdel A.

doi:10.1016/j.lfs.2008.11.006

Cited by 2 publications

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References 37 publications

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“…Total nitrate/nitrite (NOx) concentrations of LC homogenates and plasma from blood samples were determined by standard colorimetric assay (kit from Cayman Chemical, Ann Arbor, MI) using Griess reagents and a 3‐hour incubation period. Values for LC homogenates were normalized to protein as in our recent studies (El‐Mas and Abdel‐Rahman, 2009; El‐Mas et al., 2008).…”

Section: Methodsmentioning

confidence: 99%

“…injections (time of peak clonidine–ethanol behavioral synergy) and processed for measurements of protein levels of p42/44 MAPK (p‐ERK1/2) and phosphorylated neuronal (p‐nNOS) and endothelial (p‐eNOS) NOS by Western blot as described in our previous study (Bender and Abdel‐Rahman, 2009). Total nitrate/nitrite (NOx) levels in the LC tissue homogenates were also determined as in our previous studies (El‐Mas and Abdel‐Rahman, 2009; El‐Mas et al., 2008). Behavioral testing was conducted in 2 additional groups of rats, which were pretreated with the p‐ERK1/2 inhibitor PD98059 (6 μg, i.c.)…”

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confidence: 99%

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Differential Central NOS‐NO Signaling Underlies Clonidine Exacerbation of Ethanol‐Evoked Behavioral Impairment

Bender

Abdel‐Rahman

2010

Alcoholism Clin & Exp Res

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Background The molecular mechanisms that underlie clonidine exacerbation of behavioral impairment caused by ethanol are not fully known. We tested the hypothesis that NOS-NO signaling in the locus coeruleus (LC) is implicated in this phenomenon. Methods Male, Sprague-Dawley rats, with intracisternal and jugular vein cannulae implanted 6 days earlier, were tested for drug-induced behavioral impairment. The latter was assessed as the duration of loss of righting reflex (LORR) and rotorod performance every 15 min until the rat recovered to the baseline walk criterion (180 s). In a separate cohort, we measured p-nNOS, p-eNOS, and p-ERK1/2 in the LC following drug treatment, vehicle, or NOS inhibitor. Results Rats that received clonidine (60 μg/kg, i.v.) followed by ethanol (1 or 1.5 g/kg, i.v.) exhibited synergistic impairment of rotorod performance. Intracisternal (i.c.) pretreatment with non-selective NOS inhibitor L-NAME (0.5 mg) or selective nNOS inhibitor N-propyl-L-arginine (NPLA, 1 μg) exacerbated the impairment of rotorod performance caused by clonidine-ethanol combination. Exacerbation of behavioral impairment was caused by L-NAME enhancement of the effect of ethanol, not clonidine. L-NAME did not influence blood ethanol levels; thus, the interaction was pharmacodynamic. LORR caused by clonidine (60 μg/kg, i.v.)-ethanol (1 g/kg, i.v.) combination was abolished by selective inhibition of central eNOS (L-NIO, 10 μg i.c.) but not by nNOS inhibition under the same conditions. Western blot analyses complemented the pharmacological evidence by demonstrating that clonidine-ethanol combination inhibits phosphorylation (activation) of nNOS (p-nNOS) and increases the level of phosphorylated eNOS (p-eNOS) in the LC; the change in p-nNOS was paralleled by similar change in LC p-ERK1/2. NOS inhibitors alone did not affect the level of nitrate/nitrite, p-nNOS, p-eNOS, or p-ERK1/2 in the LC. Conclusions Alterations in NOS-derived NO in the LC underlie clonidine-ethanol induced behavioral impairment. A decrease in nNOS activity, due at least partly to a reduction in nNOS phosphorylation, mediates rotorod impairment, while enhanced eNOS activity contributes to LORR, elicited by clonidine-ethanol combination.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%