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

Abstract

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 (H1histaminergic-receptor antagonist) significantly reduced the C48/80-induced increase in PRA when given intracerebroventricularly, but not when given intravenously. In contrast, metiamide (H2histaminergic-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).

Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human hearts

“…This is a condensation product of p-methoxyphenethyl-methylamine and formaldehyde originally described as histamine liberator (2,43). Later, it was demonstrated that histamine can be released along with other compounds like 5-HT and epinephrine (9,36). As shown in Fig.…”

Mast Cell Stabilization Decreases Cardiomyocyte and LV Function in Dogs With Isolated Mitral Regurgitation

“…This chronically administered dose is comparable to that used to prevent mast cell degranulation in dogs. 15,16 Treatment was started 24 hours after MR induction. Only 5 of 9 untreated MR dogs (male = 3; female = 2) and 4 of 6 MR dogs treated with MCS (male = 3; female = 1) survived to four months.…”

“…15,16 Ketotifen is a histamine H 1 receptor and calcium entry antagonist that inhibits the release of leukotrienes and improves β-adrenoreceptor sensitivity. 9 Here we show that MCS does not attenuate eccentric LV remodeling nor does it preserve interstitial collagen after four months of MR in the dog.…”

An Overview of the Physiological and Pathological Role of Mast Cells in the Central Nervous System

“…This can also be proved by the fact that H1 receptor blockers decrease cortisol secretions. In animal studies, histamine release from brain MC may increase renin and epinephrine secretion (through splanchnic nerves) and antidiuretic hormone secretion (through central nervous system) [20,21]. They also seem to influence pituitary-thyroid action.…”