Stimulation of brain mast cells by compound 48/80, a histamine liberator, evokes renin and vasopressin release in dogs

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2008-03, Vol.294 (3), p.R689-R698
• Main Authors: Matsumoto, Itsuro, Inoue, Yasuhisa, Shimada, Toshio, Matsunaga, Tomoe, Aikawa, Tadaomi
• Format: Article
• Language: English
• Subjects: Animals; Brain; Brain - cytology; Brain Chemistry - drug effects; Catecholamines - blood; Cell Degranulation - drug effects; Dogs; Drug Synergism; Histamine; Histamine H1 Antagonists - pharmacology; Histamine H2 Antagonists - pharmacology; Histamine Release - drug effects; Hormones; Injections, Intraventricular; Ketotifen - pharmacology; Kidney - drug effects; Kidney - physiology; Male; Mast Cells - drug effects; Mast Cells - metabolism; Neurons; p-Methoxy-N-methylphenethylamine - administration & dosage; p-Methoxy-N-methylphenethylamine - pharmacology; Plasma; Renin - metabolism; Splanchnic Nerves - physiology; Stimulation, Chemical; Vasopressins - metabolism
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00453.2007

1 Department of Physiology, Nagasaki University School of Medicine, Nagasaki, Japan; and 2 Department of Anatomy and Physiology, Faculty of Wellness, Kwassui Women's College, Nagasaki, Japan Submitted 26 June 2007 ; accepted in final form 14 December 2007 Because degranulation of brain mast cells activates adrenocortical secretion (41, 42), we examined whether activation of such cells increases renin and vasopressin (antidiuretic hormone: ADH) secretion. For this, we administered compound 48/80 (C48/80), which liberates histamine from mast cells, to pentobarbital-anesthetized dogs. An infusion of 37.5 µg/kg C48/80 into the cerebral third ventricle evoked increases in plasma renin activity (PRA), and in plasma epinephrine (Epi) and ADH concentrations. Ketotifen (mast cell-stabilizing drug; given orally for 1 wk before the experiment) significantly reduced the C48/80-induced increases in PRA, Epi, and ADH. Resection of the bilateral splanchnic nerves (SPX) below the diaphragm completely prevented the C48/80-induced increases in PRA and Epi, but potentiated the C48/80-induced increase in ADH and elevated the plasma Epi level before and after C48/80 challenge. No significant changes in mean arterial blood pressure, heart rate, concentrations of plasma electrolytes (Na + , K + , and Cl – ), or plasma osmolality were observed after C48/80 challenge in dogs with or without SPX. Pyrilamine maleate (H 1 histaminergic-receptor antagonist) significantly reduced the C48/80-induced increase in PRA when given intracerebroventricularly, but not when given intravenously. In contrast, metiamide (H 2 histaminergic-receptor antagonist) given intracerebroventricularly significantly potentiated the C48/80-induced PRA increase. A small dose of histamine (5 µg/kg) administered intracerebroventricularly increased PRA twofold and ADH fourfold (vs. their basal level). These results suggest that in dogs, endogenous histamine liberated from brain mast cells may increase renin and Epi secretion (via the sympathetic outflow) and ADH secretion (via the central nervous system). degranulation of brain mast cells; H 1 -histaminergic antagonist; H 2 -histaminergic antagonist; splanchnicectomy Address for reprint requests and other correspondence: I. Matsumoto, Dept. of Physiology, Nagasaki Univ. School of Medicine, Nagasaki 852-8523, Japan. (e-mail: matu-itu{at}net.nagasaki-u.ac.jp )