Inhibitors of phenylethanolamine N-methyltransferase. 1. Effects of 2-cycloocytyl-2-hydroxyethylamine on rat brain and adrenal catecholamine content and blood pressure.
Acute administration of 2-cyclooctyl-2-hydroxyethylamine (CONH), a potent phenylethanolamine N-methyltransferase inhibitor, produced time- and dose-related reductions of blood pressure in spontaneously hypertensive rats (SHR). CONH did not affect the blood pressure of age-paired normotensive Wistar-Kyoto rats (WKY), or the heart rate of either animal group. CONH produced dose- and time-related reductions in epinephrine (Epi) levels in the hypothalamus and brainstem of both SHR and WKY. The drug also produced dose- and time-related reductions in hypothalamic and brainstem norepinephrine concentrations and elevations in dopamine and 3,4-dihydroxyphenylacetic acid concentrations in both SHR and WKY. CONH was about equally effective in reducing brain norepinephrine and Epi concentrations in both animal strains, but CONH was more effective in elevating brain dopamine and 3,4-dihydroxyphenylacetic acid concentrations in SHR than in WKY. Subchronic administration (3 days) of CONH produced a dose-related reduction in blood pressure in SHR, but had no affect on blood pressure in WKY. The changes in blood pressure in SHR were accompanied by a dose-related reduction in hypothalamic Epi concentrations, but the drug treatment produced no affect on the concentration of Epi in the brainstem. The results of this study suggest that brain Epi-containing neurons may be directly involved in the regulation of blood pressure or alternatively they may indirectly control cardiovascular function by modulating brain norepinephrine- and/or dopamine-neuronal activity.
D000311:Adrenal Glands / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000502:physiology*; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D004837:Epinephrine / Q000378:metabolism*; D004983:Ethanolamines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000235:genetics; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains
D004983:Ethanolamines; C036087:2-cyclooctyl-2-hydroxyethylamine; D010625:Phenylethanolamine N-Methyltransferase; D009638:Norepinephrine; D004837:Epinephrine