Clinical Experience with Blockade of the Renin-Angiotensin-Aldosterone System by an Oral Converting Enzyme Inhibitor (SQ 14,225, Captopril) in Hypertensive Patients

Case, David B.; Atlas, Steven A.; Laragh, John H.; Sealey, Jean E.; Sullivan, Patricia A.; McKinstry, Doris N.

doi:10.1007/978-1-4615-9179-5_15

Cited by 50 publications

(76 citation statements)

References 16 publications

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“…Both angiotensin converting enzyme (ACE) inhibitors and P-adrenoceptor blocking agents have become established as effective and well tolerated antihypertensive agents (Case et al, 1978, Prichard & Owens, 1986. Although these agents have been shown to reduce blood pressure in several forms of human hypertension, a number of studies have demonstrated that hypertension cannot be completely controlled by either type of drug alone.…”

Section: Introductionmentioning

confidence: 99%

“…However, when we attempted to hybridise P-adrenoceptor blocking agents based on a benzene (atenolol like) or naphthalene (propranolol like) nucleus with an ACE inhibitor of the enalapril type the resultant compounds failed to exhibit dual activity (Allan et al, 1986a). However, we discovered that when the P-adrenoceptor blocking agent, pindolol and an ACE inhibitor of the enalapril type were used as templates for chemical hybridisation, the resultant chemical hybrid had dual activity (Allan et al, 1986b (Buhler et al, 1972;Case et al, 1978) it is quite clear that P-adrenoceptor blocking agents can exert hypotensive actions independent of this system e.g. direct effects on the heart and central actions (Prichard & Owens, 1986).…”

Section: Introductionmentioning

confidence: 99%

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BW A575C, a chemically novel agent with angiotensin converting enzyme inhibitor and β‐adrenoceptor‐blocking properties

Allan

Cambridge

Hardy

et al. 1987

British J Pharmacology

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) is a chemically novel agent which exhibits in a single molecule both angiotensin converting enzyme (ACE) inhibition and P-adrenoceptor-blocking properties.2 BW A575C produced a competitive blockade of heart rate responses to isoprenaline in a guinea-pig right atrial preparation (pKB 7.18 ± 0.05, cf. pindolol 8.9 ± 0.7). BW A575C inhibited a partially purified preparation of ACE obtained from rabbit lung (IC50 10.7 + 2.1 nM, cf. enalaprilat, 4.4 ± 0.8 nM).3 Intravenous administration of BW A575C (1-100 tgkg-' min-')to the pithed rat inhibited in a dose-dependent fashion both angiotensin I-induced pressor responses and isoprenaline-induced tachycardia. Dose-ratios obtained from such studies demonstrated that, in this preparation, BW A575C was approximately 100 times more active as an ACE inhibitor than as a P-adrenoceptor blocking agent. 4 Intravenous administration of BW A575C (I mg kg-') to the conscious rat inhibited angiotensin Iinduced pressor responses, being approximately equipotent to enalapril and 10 times more potent than captopril. At the same dose, BW A575C had a similar duration of action as an ACE inhibitor to enalapril. 5 Intravenous administration of BW A575C (I mg kg-') to either conscious dogs or rats inhibited both angiotensin I-induced pressor responses and isoprenaline-induced heart rate responses. Doseratios obtained from such studies demonstrated that in these species, BW A575C was 2-10 times more active as an ACE inhibitor than as a P-adrenoceptor blocking agent.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

BW A575C, a chemically novel agent with angiotensin converting enzyme inhibitor and β‐adrenoceptor‐blocking properties

Allan

Cambridge

Hardy

et al. 1987

British J Pharmacology

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“…Captopril can reduce blood pressure both in renovascular and essential hypertension (Atkinson & Robertson 1979;Gavras et al, 1978;Bravo & Tarazi, 1979;Atlas et al, 1979). Opinions differ whether its blood-pressure lowering effect in essential hypertension is correlated with plasma renin activity (Laragh, 1978;Case et al, 1978;Karlberg etal., 1981;Bravo & Tarazi, 1979;Gavras etal., 1978;Johnston et al, 1979). That captopril can reduce blood pressure independently of circulating renin and angiotensin II concentrations is shown by its antihypertensive effect in anephric patients (Vaughan et al, 1979;De Bruyn etal., 1980).…”

Section: Introductionmentioning

confidence: 99%

Captopril and atenolol combined with hydrochlorothiazide in essential hypertension.

Andrén¹,

Karlberg²,

Svensson³

et al. 1982

Brit J Clinical Pharma

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1 Fifty-seven patients with mild or moderate essential hypertension, mean age 50 (range 31-69) were randomised to treatment with either captopril or atenolol. Twenty-six patients in each group completed the study. 2 Captopril (25-50 mg three times daily) and atenolol (50-100 mg once daily) caused a highly significant fall in blood pressure both supine and standing. 3 When hydrochlorothiazide (25-50 mg once daily) was added a further fall in blood pressure was observed in both groups. 4 Captopril as single drug caused no significant change in heart rate, while atenolol significantly reduced heart rate both supine and standing. 5 Two patients were excluded from the captopril group, one because of a reversible loss of taste and the other because of dizziness. Three patients were excluded from the atenolol group, two because of bradyarrhythmias and one because of inadequate blood pressure response. 6 Both captopril and atenolol were found to be effective antihypertensive agents, suitable for the treatment of essential hypertension.

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“…In fact, our initial experience with captopril published in 1978 described a hypotensive episode following captopril in a patient with accelerated hypertension who had previously received a dose of furosemide. 1 The hypotension was promptly and safely reversed by placing the patient in the head-down Trendelenberg position and infusing normal saline. As a result of this and several other similar experiences, as a standby procedure we now are prepared to infuse saline into patients who need immediate captopril treatment, particularly those who have received a diuretic or have any question of being volumedepleted.…”

Section: Authors' Responsementioning

confidence: 99%

Clinical use of captopril.

Hoorntje¹,

Donker²

1981

Hypertension

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Clinical Experience with Blockade of the Renin-Angiotensin-Aldosterone System by an Oral Converting Enzyme Inhibitor (SQ 14,225, Captopril) in Hypertensive Patients

Cited by 50 publications

References 16 publications

BW A575C, a chemically novel agent with angiotensin converting enzyme inhibitor and β‐adrenoceptor‐blocking properties

BW A575C, a chemically novel agent with angiotensin converting enzyme inhibitor and β‐adrenoceptor‐blocking properties

Captopril and atenolol combined with hydrochlorothiazide in essential hypertension.

Clinical use of captopril.

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