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Titolo:
Effects of ridogrel, a thromboxane synthase inhibitor and receptor antagonist, on blood pressure in the spontaneously hypertensive rat
Autore:
Quest, DW; Wilson, TW;
Indirizzi:
RoyaltUniv Hosp, Dept Med, Div Clin Pharmacol, Cardiovasc Risk Factor Reduc Royal Univ Hosp Saskatoon SK Canada S7N 0W0 Cardiovasc Risk Factor Reduc
Titolo Testata:
JAPANESE JOURNAL OF PHARMACOLOGY
fascicolo: 4, volume: 78, anno: 1998,
pagine: 479 - 486
SICI:
0021-5198(199812)78:4<479:EORATS>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROSTAGLANDIN ENDOPEROXIDE METABOLISM; PROSTACYCLIN; PLATELET; STROKE; RENIN; 6-KETO-PROSTAGLANDIN-F-1-ALPHA; ANGIOTENSIN; REDIRECTION; CIRCULATION; PROFILE;
Keywords:
blood pressure; renal prostanoid; ridogrel; thromboxane;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Wilson, TW RoyaltUniv Hosp, Dept Med, Div Clin Pharmacol, Cardiovasc Risk Factor Reduc Royal Univ Hosp 103 Hosp Dr Saskatoon SK Canada S7N 0W0 r Reduc
Citazione:
D.W. Quest e T.W. Wilson, "Effects of ridogrel, a thromboxane synthase inhibitor and receptor antagonist, on blood pressure in the spontaneously hypertensive rat", JPN J PHARM, 78(4), 1998, pp. 479-486

Abstract

Ridogrel is a dual acting thromboxane synthase inhibitor/TP receptor antagonist. We examined the effects of single and multiple doses on systolic blood pressure in stroke-prone spontaneously hypertensive rats. Single doses of ridogrel (5 to 125 mg/kg) did not affect systolic blood pressure or furosemide-stimulated excretion rates of thromboxane B-2 or 6-keto-prostaglandinF-1 alpha, although ex vivo serum thromboxane B-2 was dose-dependently reduced up to 95%. In contrast, repeated dosing (7 days) with ridogrel (3 to 25 mg/kg/day), had an antihypertensive effect in 12-week-old stroke-prone spontaneously hypertensive rats. At 25 mg/kg/day, ridogrel reduced systolic blood pressure from 200 +/- 6.1 to 173 +/- 6.7 mmHg (n = 12, P<0.01). Ridogrel dose-dependently reduced serum thromboxane B-2 and increased plasma renin activity. Unlike single doses, repeated dosing reduced urinary thromboxane B-2 excretion (from 103 +/- 7 ng/day to 49 +/- 10 ng/day, P<0.01) while preserving 6-keto-prostaglandin F-1 alpha excretion. Ketoprofen, a cyclo-oxygenase inhibitor, (10 mg/kg/day for 7 days), depressed urine 6-keto-prostaglandin F-1 alpha in addition to attenuating serum and urine thromboxane B-2. Ketoprofen prevented the antihypertensive effects of ridogrel. Ridogrel did not lower systolic blood pressure in Sprague-Dawley rats. We conclude that the antihypertensive effect of ridogrel involves preserving renal prostaglandin synthesis during thromboxane attenuation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 23:06:31