Mechanisms of histamine-induced relaxation in bovine small adrenal cortical arteries

Abstract

Adrenal steroidogenesis is closely correlated with increases in adrenal blood flow. Many reports have studied the regulation of adrenal blood flow in vivo and in perfused glands, but until recently few studies have been conducted on isolated adrenal arteries. The present study examined vasomotor responses of isolated bovine small adrenal cortical arteries to histamine, an endogenous vasoactive compound, and its mechanism of action. In U-46619-precontracted arteries, histamine (10(-9)-5 x 10(-6) M) elicited concentration-dependent relaxations. The relaxations were blocked by the H(1) receptor antagonists diphenhydramine (10 microM) or mepyramine (1 microM) (maximal relaxations of 18 +/- 6 and 22 +/- 6%, respectively, vs. 55 +/- 5% of control) but only partially inhibited by the H(2) receptor antagonist cimetidine (10 microM) and the H(3) receptor antagonist thioperamide (1 microM). Histamine-induced relaxations were also blocked by the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA, 30 microM; maximal relaxation of 13 +/- 7%) and eliminated by endothelial removal or L-NA combined with the cyclooxgenase inhibitor indomethacin (10 microM). In the presence of adrenal zona glomerulosa (ZG) cells, histamine did not induce further relaxations compared with histamine alone. Histamine (10(-7)-10(-5) M) concentration-dependently increased aldosterone production by adrenal ZG cells. Compound 48/80 (10 microg/ml), a mast cell degranulator, induced significant relaxations (93 +/- 0.6%), which were blocked by L-NA plus indomethacin or endothelium removal, partially inhibited by the combination of the H(1), H(2), and H(3) receptor antagonists, but not affected by the mast cell stabilizer sodium cromoglycate (1 mM). These results demonstrate that histamine causes direct relaxation of small adrenal cortical arteries, which is largely mediated by endothelial NO and prostaglandins via H(1) receptors. The potential role of histamine in linking adrenal vascular events and steroid secretion requires further investigation.

Differences in the expression of histamine-related genes and proteins in normal human adrenal cortex and adrenocortical tumors

“…Only few studies on the adrenocortical actions of histamine have been reported to date, and these presented contradictory results [27][28][29][30] that may be in part due to species differences. Yoshida et al failed to detect any effect of histamine on basal cortisol secretion of isolated bovine adrenocortical cells; however, if co-cultured with bovine adrenomedullary cells, histamine dose-dependently induced cortisol secretion acting indirectly via the stimulation of adrenomedullary catecholamine secretion [27].…”

“…Expression of histamine-related genes and proteins was detected in both normal and neoplastic adrenocortical tissues; thus, the whole histaminergic machinery including biosynthetic and degrading enzymes as well as histamine receptors were found to be present. Since histamine mainly acts in a paracrine fashion, its secretion by adrenocortical cells might influence steroid biosynthesis, adrenocortical blood flow [30,32], immune response, etc. Further, experimental studies (e.g., actions of histamine receptor agonists and antagonists on adrenocortical cancer cell lines) are needed to clarify the relevance of histamine in the normal adrenal cortex and to examine the consequences of decreased histamine biosynthesis and altered receptor repertoire in adrenocortical tumor development.…”

Characterization ofl-arginine transport in adrenal cells: effect of ACTH

“…Therefore, L-arginine efflux in exchange for neutral amino acids and Na ϩ could be a mechanism through which steroidogenic cells provide other NO producing adrenal cells (endothelial and neural cells) with this amino acid. By this mechanism, L-arginine-derived NO synthesized by endothelial cells within the adrenal cortex could be involved in the regulation of blood flow by histamine (42) or angiotensin II (16) or in the effects of the vascular endothelial growth factor or endocrine gland derived-VEGF (34a). Moreover, it is tempting to speculate that NO produced by adrenal endothelial cells could be involved in the modulation of steroid secretion in the ZF because it was demonstrated in zona glomerulosa cells (19).…”

Role of Mast Cells in the Control of Aldosterone Secretion

“…1a, c) [25][26][27]. These perivascular mast cells have been shown to be involved in the control of adrenal blood flow in rat and cattle [25,30]. Globally, mast cells are present in adrenals of all studied species from amphibians to mammals.…”