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Titolo:
Antihypertensive effects of a mixed endothelin-A- and -B-receptor antagonist, J-104132, were augmented in the presence of an AT1-receptor antagonist,MK-954
Autore:
Ikeda, T; Ohta, H; Okada, M; Kawai, N; Nakao, R; Siegl, PKS; Kobayashi, T; Miyauchi, T; Nishikibe, M;
Indirizzi:
Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Pharmacol Lab, Tsukuba, Ibaraki3002611, Japan Banyu Pharmaceut Co Ltd Tsukuba Ibaraki Japan 3002611 araki3002611, Japan Univ Tsukuba, Inst Clin Med, Dept Internal Med, Div Cardiovasc, Tsukuba, Ibaraki 305, Japan Univ Tsukuba Tsukuba Ibaraki Japan 305 ovasc, Tsukuba, Ibaraki 305, Japan Merck Res Labs, W Point, PA USA Merck Res Labs W Point PA USAMerck Res Labs, W Point, PA USA
Titolo Testata:
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
, volume: 36, anno: 2000, supplemento:, 1
pagine: S337 - S341
SICI:
0160-2446(2000)36:<S337:AEOAME>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
SPONTANEOUSLY HYPERTENSIVE RATS; SALT-SENSITIVE HYPERTENSION; ACTIVATION; BLOCKADE; POTENT;
Keywords:
endothelin (ET); J-104132 (L-753,037); Losartan (MK-954); spontaneously hypertensive rat (SHR); Dahl salt-sensitive rats;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
13
Recensione:
Indirizzi per estratti:
Indirizzo: Ikeda, T Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Pharmacol Lab, Okubo 3, Tsukuba, Ibaraki 3002611, Japan Banyu Pharmaceut Co Ltd Okubo 3 Tsukuba Ibaraki Japan 3002611 pan
Citazione:
T. Ikeda et al., "Antihypertensive effects of a mixed endothelin-A- and -B-receptor antagonist, J-104132, were augmented in the presence of an AT1-receptor antagonist,MK-954", J CARDIO PH, 36, 2000, pp. S337-S341

Abstract

The single oral administration of a mixed endothrlin-A- and -B- (ETA/ETB) receptor antagonist, J-103132 (L-753,037) decreased the blood pressure in conscious spontaneously hypertensive rats (SHR), stroke-prone SI-IR (SHRSP) and Dahl salt-sensitive hypertensive rats fed high-salt diet (DS-H) at doses of 3 and 10 mg/kg, with a duration of approximately 24 h. The magnitude of the antihypertensive effects was greater in DS-H than in SHR and SHRSP. Preproendothelin-1 mRNA expression in the kidney and aorta was greater (about twofold) in DS-H than that in normotensive Dahl salt-resistant rats fed high-salt diet (DR-H), while there was no difference in preproendothelin-1 mRNA expression between SHR and Wistar Kyoto rats (WKY). An AT1-receptor antagonist, MK-954 (Losartan), also attenuated hypertension in SHR and SHRSP at oral doses of 3 and 10 mg/kg, but had no effect in DS-H. The concomitant treatment with MK-954 and J-104132 showed additive antihypertensive effectsin SHR and SHRSP. In DS-H, MK-954 potentiated the antihypertensive effectsof J-104132. From these results, we sug gest that: (1) the contribution ofendothelin (ET) to the maintenance of hypertension is greater in salt-sensitive hypertensive models than in SHR and SHRSP; (2) the antihypertensive efficacy of ETA/ETB blockade is augmented by AT1-receptor blockade; (3) ET blockers alone or in combination with AT1 antagonists could be useful in thetreatment of hypertension for patients who do not respond adequately to renin-angiotensin system inhibitors alone.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 00:49:23