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.