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Titolo:
ENDOPEPTIDASE-24.11 INHIBITION BY SCH-42495 IN ESSENTIAL-HYPERTENSION
Autore:
RICHARDS AM; CROZIER IG; KOSOGLOU T; RALLINGS M; ESPINER EA; NICHOLLS MG; YANDLE TG; IKRAM H; FRAMPTON C;
Indirizzi:
PRINCESS MARGARET HOSP,DEPT CARDIOL CHRISTCHURCH 2 NEW ZEALAND PRINCESS MARGARET HOSP,DEPT ENDOCRINOL CHRISTCHURCH 2 NEW ZEALAND SCHERING PLOUGH CORP,RES INST KENILWORTH NJ 00000 SCHERING PLOUGH PTY LTD BAULKHAM HILLS NSW AUSTRALIA
Titolo Testata:
Hypertension
fascicolo: 1, volume: 22, anno: 1993,
pagine: 119 - 126
SICI:
0194-911X(1993)22:1<119:EIBSIE>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
ATRIAL-NATRIURETIC-FACTOR; BLOOD-PRESSURE; NEUTRAL ENDOPEPTIDASE; CHRONIC INFUSION; CONSCIOUS SHR; PEPTIDE; RESPONSES; SODIUM; RATS; RADIOIMMUNOASSAY;
Keywords:
MEMBRANE METALLOENDOPEPTIDASE; ATRIAL NATRIURETIC FACTOR; RENIN-ANGIOTENSIN SYSTEM; CATECHOLAMINES; NATRIURESIS; BLOOD PRESSURE; HYPERTENSION, ESSENTIAL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
A.M. Richards et al., "ENDOPEPTIDASE-24.11 INHIBITION BY SCH-42495 IN ESSENTIAL-HYPERTENSION", Hypertension, 22(1), 1993, pp. 119-126

Abstract

The detailed integrated renal, hormonal, and hemodynamic effects of acute (first dose) and established (4 days) inhibition of endopeptidase24.11 by SCH 42495 (200 mg, every 12 hours) were documented in eight patients with essential hypertension in a double-blind, balanced random-order, crossover study. SCH 42495 suppressed plasma endopeptidase activity (>90%, P<.001) for the duration of the dosing period. Initially, plasma atrial natriuretic factor levels increased markedly (+123%, P<.01) and remained elevated, although to a lesser extent (+34%, P<.01), with established enzyme inhibition. Cyclic guanosine monophosphate in both plasma and urine remained elevated throughout the treatment period. Significant augmentation of sodium excretion in excess of placebovalues (96+/-27 mmol sodium, P<.001) was established in the initial 24 hours of dosing but later became attenuated, with a mild antinatriuresis (P<.01) in the latter 3 days of treatment. Blood pressure, heart rate, the renin-angiotensin-aldosterone system, and plasma norepinephrine levels were all initially (first dose) unchanged. With establishedenzyme inhibition (day 4), however, blood pressure was significantly lower (mean 24-hour values, 9.3+/-3/-3.8+/-1 mm Hg, P<.05 for both systolic and diastolic pressures) than matched placebo values, whereas heart rate was higher (2.7+/-1 beats per minute, P<.01). Mean 24-hour values of plasma renin activity (+33%, P<.05), aldosterone (+36%, P<.05), and norepinephrine (+40%, P<.001) were all clearly increased above placebo values with established enzyme inhibition. In summary, inhibition of endopeptidase 24.11 in essential hypertension leads to both acute and sustained increases in plasma atrial natriuretic factor and cyclic guanosine monophosphate, with an associated acute natriuresis. The renin-angiotensin-aldosterone and sympathetic nervous systems exhibit delayed activation, and these latter compensatory responses may limit the antihypertensive effect of endopeptidase inhibition.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 21:23:54