title: Mast cell chymase in the ischemic kidney of severe unilateral renovascular hypertension.
abstract: Chymase degrades angiotensin I (AI) to form angiotensin II (AII), probably constituting a bypass of the renin-angiotensin cascade. Chymase activity increases in some vascular diseases. In the kidney, an increase in chymase activity was reported in an animal model of ischemic kidney of renovascular hypertension (RVH); however, no such evidence has been provided in humans. We treated a 64-year-old patient with severe unilateral RVH and atherosclerosis, for whom removal of the ischemic kidney was the only option. Using immunohistochemical staining, we investigated chymase activity in the removed kidney and associated artery and vein. An increase in chymase activity, together with mast cells infiltrating the interstitium, was observed where interstitial fibrosis was seen. In the renal artery, where severe atherosclerosis was seen, and also in the vein, mast cell infiltration in the adventitia was accompanied by chymase. The captopril test showed an increase in serum aldosterone level, with a concomitant increase in plasma renin activity and decrease in blood pressure. Because the decrease in blood pressure implies a decrease in circulatory AII levels, it is plausible that in this patient, chymase had a role in AII formation in the adrenal gland to stimulate aldosterone secretion. Thus, by means of captopril, AI levels increased, and chymase may have produced AII in loci tissues, which, in turn, stimulated aldosterone secretion. This is the first report of an increase in chymase activity in the interstitium of an ischemic kidney and renal artery and vein in a patient with RVH and atherosclerosis.
authors.affiliation: Department of Internal Medicine, Osaka City General Hospital, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Morikawa
authors.forename: Masahito
authors.initials: M
authors.lastname: Imanishi
authors.forename: Hisa
authors.initials: H
authors.lastname: Suzuki
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Okada
authors.forename: Michiaki
authors.initials: M
authors.lastname: Okumura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Konishi
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Shinji
authors.initials: S
authors.lastname: Takai
authors.forename: Mizuo
authors.initials: M
authors.lastname: Miyazaki
mesh_terms: D015901:Angiography, Digital Subtraction; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000096:biosynthesis*; D001161:Arteriosclerosis / Q000150:complications* / Q000201:enzymology; D002216:Captopril; D053818:Chymases; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000139:chemically induced; D006978:Hypertension, Renovascular / Q000000981:diagnostic imaging / Q000201:enzymology / Q000209:etiology / Q000473:pathology* / Q000601:surgery; D007511:Ischemia / Q000150:complications / Q000473:pathology* / Q000601:surgery; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D008407:Mast Cells / Q000201:enzymology*; D008875:Middle Aged; D009392:Nephrectomy; D012077:Renal Artery / Q000201:enzymology; D012078:Renal Artery Obstruction / Q000150:complications* / Q000201:enzymology; D012082:Renal Veins / Q000201:enzymology; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology; D012697:Serine Endopeptidases / Q000032:analysis* / Q000502:physiology; D012907:Smoking
chemical_list: D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D012697:Serine Endopeptidases; D053818:Chymases; D012083:Renin