Literature DB >> 6266576

Non-sulfhydryl-containing angiotensin-converting enzyme inhibitor (MK421): evidence for role of renin system in normotensive subjects.

G A MacGregor, N D Markandu, J Bayliss, J E Roulston, M Squires, J J Morton.   

Abstract

A non-sulfhydryl-containing inhibitor of angiotensin-converting enzyme (MK421) was given as a single dose in a randomised double-blind cross-over trial using 20 mg and 5 mg of MK-421 or matched placebo to nine normotensive volunteers receiving a sodium intake of 150 mmol (mEq) daily. The two dosages of MK-421 caused similar, significant falls in supine and standing blood pressure, which were maximum four to six hours after dosing (9.5-11.0% fall). With this fall in blood pressure there was a significant fall in activity of angiotensin-converting enzyme and in concentrations of plasma angiotensin II and aldosterone and a rise in plasma renin activity. Placebo caused no significant change in blood pressure or blood measurements. The study showed that MK-421 inhibits angiotensin-converting enzyme activity and lowers blood pressure in normotensive subjects. It strongly suggested that the renin system plays an important part in maintaining blood pressure in normotensive subjects receiving normal sodium intake. The results also suggest that this non-sulfhydryl-containing converting-enzyme inhibitor will be an effective blood-pressure-lowering drug in patients with blood pressure. A single dose of 5 mg was as effective at lowering blood pressure as a single dose of 20 mg.

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Year:  1981        PMID: 6266576      PMCID: PMC1506640          DOI: 10.1136/bmj.283.6288.401

Source DB:  PubMed          Journal:  Br Med J (Clin Res Ed)        ISSN: 0267-0623


  11 in total

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Authors:  C F George; P J Lewis; A Petrie
Journal:  Br Heart J       Date:  1975-08

2.  Estimation of angiotensin II concentration in human plasma by radioimmunoassay. Some applications to physiological and clinical states.

Authors:  G Düsterdieck; G McElwee
Journal:  Eur J Clin Invest       Date:  1971-11       Impact factor: 4.686

3.  Evidence that the area postrema mediates the central cardiovascular response to angiotensin II.

Authors:  M D Joy; R D Lowe
Journal:  Nature       Date:  1970-12-26       Impact factor: 49.962

4.  Captopril-associated agranulocytosis.

Authors:  P van Brummelen; R Willemze; W D Tan; J Thompson
Journal:  Lancet       Date:  1980-01-19       Impact factor: 79.321

5.  Nephrotic syndrome in patient on captopril.

Authors:  E J Prins; S J Hoorntje; J J Weening; A J Donker
Journal:  Lancet       Date:  1979-08-11       Impact factor: 79.321

6.  A new class of angiotensin-converting enzyme inhibitors.

Authors:  A A Patchett; E Harris; E W Tristram; M J Wyvratt; M T Wu; D Taub; E R Peterson; T J Ikeler; J ten Broeke; L G Payne; D L Ondeyka; E D Thorsett; W J Greenlee; N S Lohr; R D Hoffsommer; H Joshua; W V Ruyle; J W Rothrock; S D Aster; A L Maycock; F M Robinson; R Hirschmann; C S Sweet; E H Ulm; D M Gross; T C Vassil; C A Stone
Journal:  Nature       Date:  1980-11-20       Impact factor: 49.962

7.  Measurement of plasma renin activity by radioimmunoassay after prolonged cold storage.

Authors:  J E Roulston; G A MacGregor
Journal:  Clin Chim Acta       Date:  1978-08-15       Impact factor: 3.786

8.  Maintenance of blood pressure by the renin-angiotensin system in normal man.

Authors:  G A MacGregor; N D Markandu; J E Roulston; J C Jones; J J Morton
Journal:  Nature       Date:  1981-05-28       Impact factor: 49.962

9.  Essential hypertension: effect of an oral inhibitor of angiotensin-converting enzyme.

Authors:  G A MacGregor; N D Markandu; J E Roulston; J C Jones
Journal:  Br Med J       Date:  1979-11-03

Review 10.  George C. Griffith lecture. The role of renin in normal and pathological cardiovascular homeostasis.

Authors:  E Haber
Journal:  Circulation       Date:  1976-12       Impact factor: 29.690

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  17 in total

Review 1.  Safety profiles of the angiotensin-converting enzyme inhibitors.

Authors:  N J Warner; J E Rush
Journal:  Drugs       Date:  1988       Impact factor: 9.546

Review 2.  Angiotensin converting enzyme inhibitors and moderate hypertension.

Authors:  D McAreavey; J I Robertson
Journal:  Drugs       Date:  1990-09       Impact factor: 9.546

3.  The effect of enalapril (MK421), an angiotensin converting enzyme inhibitor, on the conscious pregnant ewe and her foetus.

Authors:  F Broughton Pipkin; C P Wallace
Journal:  Br J Pharmacol       Date:  1986-03       Impact factor: 8.739

4.  The effect of the converting enzyme inhibitor HOE 498 on the renin angiotensin system of normal volunteers.

Authors:  J P Bussien; J Nussberger; M Porchet; B Waeber; H R Brunner; M Perisic; M J Tansey; M Bomm; P Hajdu
Journal:  Naunyn Schmiedebergs Arch Pharmacol       Date:  1985-03       Impact factor: 3.000

Review 5.  Drug-induced taste and smell disorders. Incidence, mechanisms and management related primarily to treatment of sensory receptor dysfunction.

Authors:  R I Henkin
Journal:  Drug Saf       Date:  1994-11       Impact factor: 5.606

Review 6.  The renin-angiotensin system in the control of systemic arterial pressure.

Authors:  A B Ribeiro; O Kohlmann; M A Saragoça; O Marson; O L Ramos
Journal:  Drugs       Date:  1985       Impact factor: 9.546

7.  Markedly elevated specific renin levels in the adrenal in genetically hypertensive rats.

Authors:  M Naruse; T Inagami
Journal:  Proc Natl Acad Sci U S A       Date:  1982-05       Impact factor: 11.205

8.  Enalapril (MK421) and its lysine analogue (MK521): a comparison of acute and chronic effects on blood pressure, renin-angiotensin system and sodium excretion in normal man.

Authors:  G P Hodsman; J R Zabludowski; C Zoccali; R Fraser; J J Morton; G D Murray; J I Robertson
Journal:  Br J Clin Pharmacol       Date:  1984-03       Impact factor: 4.335

9.  Converting-enzyme inhibitor enalapril (MK421) in treatment of hypertension with renal artery stenosis.

Authors:  G P Hodsman; J J Brown; D L Davies; R Fraser; A F Lever; J J Morton; G D Murray; J I Robertson
Journal:  Br Med J (Clin Res Ed)       Date:  1982-12-11

Review 10.  An overview of the clinical pharmacology of enalapril.

Authors:  R O Davies; H J Gomez; J D Irvin; J F Walker
Journal:  Br J Clin Pharmacol       Date:  1984       Impact factor: 4.335

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