title: Enhanced catabolism to acetaldehyde in rostral ventrolateral medullary neurons accounts for the pressor effect of ethanol in spontaneously hypertensive rats.
abstract: We have previously shown that ethanol microinjection into the rostral ventrolateral medulla (RVLM) elicits sympathoexcitation and hypertension in conscious spontaneously hypertensive rats (SHRs) but not in Wistar-Kyoto (WKY) rats. In this study, evidence was sought to implicate the oxidative breakdown of ethanol in this strain-dependent hypertensive action of ethanol. Biochemical experiments revealed significantly higher catalase activity and similar aldehyde dehydrogenase (ALDH) activity in the RVLM of SHRs compared with WKY rats. We also investigated the influence of pharmacological inhibition of catalase (3-aminotriazole) or ALDH (cyanamide) on the cardiovascular effects of intra-RVLM ethanol or its metabolic product acetaldehyde in conscious rats. Compared with vehicle, ethanol (10 μg/rat) elicited a significant increase in blood pressure in SHRs that lasted for the 60-min observation period but had no effect on blood pressure in WKY rats. The first oxidation product, acetaldehyde, played a critical role in ethanol-evoked hypertension because 1) catalase inhibition (3-aminotriazole treatment) virtually abolished the ethanol-evoked pressor response in SHRs, 2) intra-RVLM acetaldehyde (2 μg/rat) reproduced the strain-dependent hypertensive effect of intra-RVLM ethanol, and 3) ALDH inhibition (cyanamide treatment) uncovered a pressor response to intra-RVLM acetaldehyde in WKY rats similar to the response observed in SHRs. These findings support the hypothesis that local production of acetaldehyde, due to enhanced catalase activity, in the RVLM mediates the ethanol-evoked pressor response in SHRs.
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine, East Carolina University, Greenville, NC 27834, USA. mahelm@hotmail.com
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: El-Mas
authors.forename: Abdel A
authors.initials: AA
authors.lastname: Abdel-Rahman
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism* / Q000494:pharmacology; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D017776:Autonomic Pathways / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002374:Catalase / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics; D003484:Cyanamide / Q000494:pharmacology; D000431:Ethanol / Q000493:pharmacokinetics*; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008660:Metabolism / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012154:Reticular Formation / Q000187:drug effects / Q000502:physiology*; D013045:Species Specificity
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D003484:Cyanamide; D002374:Catalase; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde