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Titolo:
Effects of chronic neutral endopeptidase inhibition in rats with cyclosporine-induced hypertension
Autore:
Takeda, Y; Inaba, S; Furukawa, K; Fujimura, A; Miyamori, I; Mabuchi, H;
Indirizzi:
Kanazawa Univ, Sch Med, Dept Internal Med 2, Kanazawa, Ishikawa 920, JapanKanazawa Univ Kanazawa Ishikawa Japan 920 , Kanazawa, Ishikawa 920, Japan Kanazawa Univ, Sch Med, Dept Hlth Sci, Kanazawa, Ishikawa 920, Japan Kanazawa Univ Kanazawa Ishikawa Japan 920 , Kanazawa, Ishikawa 920, Japan Fukui Med Sch, Dept Internal Med 3, Fukui 91011, Japan Fukui Med Sch Fukui Japan 91011 Dept Internal Med 3, Fukui 91011, Japan Jichi Med Sch, Dept Clin Pharmacol, Minami Kawachi, Tochigi 32904, Japan Jichi Med Sch Minami Kawachi Tochigi Japan 32904 hi, Tochigi 32904, Japan
Titolo Testata:
JOURNAL OF HYPERTENSION
fascicolo: 7, volume: 18, anno: 2000,
pagine: 927 - 933
SICI:
0263-6352(200007)18:7<927:EOCNEI>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; ENDOTHELIN RECEPTOR ANTAGONIST; MESENTERIC-ARTERIES; IN-VIVO; MECHANISMS; VASOCONSTRICTION; SCH-42495; RELEASE; CELLS; GENE;
Keywords:
neutral endopeptidase inhibitor; endothelin; natriuretic peptide; cyclosporine; hypertension; nitric oxide;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Takeda, Y Kanazawa Univ, Sch Med, Dept Internal Med 2, 13-1 Takara Machi, Kanazawa, Ishikawa 920, Japan Kanazawa Univ 13-1 Takara Machi Kanazawa Ishikawa Japan 920 apan
Citazione:
Y. Takeda et al., "Effects of chronic neutral endopeptidase inhibition in rats with cyclosporine-induced hypertension", J HYPERTENS, 18(7), 2000, pp. 927-933

Abstract

Objective Cyclosporine (CysA), a potent immunosuppressant, is associated with hypertension and nephrotoxicity. Neutral endopeptidase (NEP) degrades vasoactive peptides, including the natriuretic peptides and endothelin-1 (ET-1), We conducted the present study to determine whether or not the NEP inhibitor, ecadotril, prevents cyclosporine-induced hypertension and to clarify the mechanisms responsible for the hypotensive effects of ecadotril. Design and methods We studied the chronic effects of ecadotril (30 mg/kg per day) on blood pressure; the production of ET-1 and C-type natriuretic peptide (CNP); endothelial nitric oxide synthase (eNOS) activity; and the expression of messenger RNA (mRNA), for each substance in blood vessels of CysA-induced hypertensive rats. Results CysA (25 mg/kg per day) given for 4 weeks increased the blood pressure from 116 +/- 14 mmHg to 159 +/- 15 mmHg, in rats. This increase was blunted by the co-administration of ecadotril (blood pressure: 134 +/- 14 mmHg). CysA increased plasma NEP activity. CysA increased the production of ET-1 and the expression of ET-1 mRNA without affecting CNP synthesis and endothelin converting enzyme(ECE)-1 mRNA expression. CysA decreased the eNOS activity and eNOS mRNA levels. Addition of the NEP inhibitor decreased the synthesis of ET-1 and ET-1 mRNA levels and increased the eNOS activity and the eNOS mRNA levels, Vascular CNP synthesis and ECE-1 mRNA expression in rats treated with ecadotril did not differ from those in rats treated with CysA and ecadotril. Conclusion These results indicate that chronic NEP inhibition may prevent the CysA-induced hypertension by decreasing local ET-1 synthesis and partlyincreasing vascular nitric oxide production. J Hypertens 2000, 18:927-933 (C) Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 19:08:19