title: Synergistic effects of Bay K 8644 and bradykinin on norepinephrine release in the hypothalamus of spontaneously hypertensive rats.
abstract: 1. In the present study, we examined the effects of Bay K 8644, a dihydropyridine (DHP)-sensitive Ca2+ channel agonist, and bradykinin on norepinephrine release in the hypothalamus of spontaneously hypertensive rats (SHR). 2. In the preliminary studies using Sprague-Dawley rats, Bay K 8644 by itself had no significant effects on the stimulation-evoked [3H]-norepinephrine release from hypothalamic slices. Bradykinin increased the stimulation-evoked [3H]-norepinephrine release in a dose-related fashion. The facilitatory effects of bradykinin on norepinephrine release were potentiated by Bay K 8644. 3. In SHR, Bay K 8644 significantly increased the stimulation-evoked norepinephrine release from hypothalamic slices. However, exposure of slices to Bay K 8644 caused no significant effects on norepinephrine release in Wistar-Kyoto (WKY) rats. The effects of Bay K 8644 in combination with bradykinin on the stimulation-evoked norepinephrine release were also greater in SHR than in WKY rats. 4. These results demonstrate that Bay K 8644 significantly potentiated the facilitatory effects of bradykinin on norepinephrine release in rat hypothalamus. The finding indicates a possible interaction of bradykinin with DHP-sensitive Ca2+ channels in the central nervous system. Furthermore, the pronounced effects of Bay K 8644 and bradykinin in SHR suggest that bradykinin-related Ca2+ channels might have a role in the regulation of norepinephrine release in the hypothalamus of SHR.
authors.affiliation: Division of Cardiology, Department of Medicine, Wakayama Medical College, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsuda
authors.forename: S
authors.initials: S
authors.lastname: Tsuda
authors.forename: I
authors.initials: I
authors.lastname: Nishio
authors.forename: Y
authors.initials: Y
authors.lastname: Masuyama
authors.forename: M
authors.initials: M
authors.lastname: Goldstein
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004558:Electric Stimulation; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
chemical_list: D002120:Calcium Channel Agonists; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D001920:Bradykinin; D009638:Norepinephrine