title: Histamine-dependent prolongation by aldosterone of vasoconstriction in isolated small mesenteric arteries of the mouse.
abstract: In arterioles, aldosterone counteracts the rapid dilatation (recovery) following depolarization-induced contraction. The hypothesis was tested that this effect of aldosterone depends on cyclooxygenase (COX)-derived products and/or nitric oxide (NO) synthase (NOS) inhibition. Recovery of the response to high K(+) was observed in mesenteric arteries of wild-type and COX-2(-/-) mice but it was significantly diminished in preparations from endothelial NOS (eNOS)(-/-) mice. Aldosterone pretreatment inhibited recovery from wild-type and COX-2(-/-) mice. The NO donor sodium nitroprusside (SNP) restored recovery in arteries from eNOS(-/-) mice, and this was inhibited by aldosterone. Actinomycin-D abolished the effect of aldosterone, indicating a genomic effect. The effect was blocked by indomethacin and by the COX-1 inhibitor valeryl salicylate but not by NS-398 (10(-6) mol/l) or the TP-receptor antagonist S18886 (10(-7) mol/l). The effect of aldosterone on recovery in arteries from wild-type mice and the SNP-mediated dilatation in arteries from eNOS(-/-) mice was inhibited by the histamine H2 receptor antagonist cimetidine. RT-PCR showed expression of mast cell markers in mouse mesenteric arteries. The adventitia displayed granular cells positive for toluidine blue vital stain. Confocal microscopy of live mast cells showed loss of quinacrine fluorescence and swelling after aldosterone treatment, indicating degranulation. RT-PCR showed expression of mineralocorticoid receptors in mesenteric arteries and in isolated mast cells. These findings suggest that aldosterone inhibits recovery by stimulation of histamine release from mast cells along mesenteric arteries. The resulting activation of H2 receptors decreases the sensitivity to NO of vascular smooth muscle cells. Aldosterone may chronically affect vascular function through paracrine release of histamine.
authors: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Denmark.
authors: Jeppe
authors: J
authors: Schjerning
authors: Torben R
authors: TR
authors: Uhrenholt
authors: Per
authors: P
authors: Svenningsen
authors: Paul M
authors: PM
authors: Vanhoutte
authors: Ole
authors: O
authors: Skøtt
authors: Boye L
authors: BL
authors: Jensen
authors: Pernille B L
authors: PB
authors: Hansen
mesh_terms: D000450:Aldosterone / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002927:Cimetidine / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006632:Histamine / Q000494:pharmacology / Q000502:physiology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D018613:Microscopy, Confocal; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D006635:Histamine H2 Antagonists; D008565:Membrane Proteins; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D002927:Cimetidine; D006632:Histamine; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse; D002118:Calcium