Use of an Angiotensin II Antagonist (Saralasin) in the Recognition of “Angiotensinogenic” Hypertension

Streeten, David H. P.; Anderson, Gunnar H.; Freiberg, J. M.; Dalakos, Theodore G.

doi:10.1056/nejm197503272921301

Cited by 282 publications

(64 citation statements)

References 6 publications

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“…When the same normals were salt loaded, P113 infusion (5-10 jig kg' min-f) caused a slight rise in lying and standing blood pressure. This effect has been reported in some hypertensives whose blood pressure did not fall during P113 infusion (Streeten et al, 1975). This rise in blood pressure cannot be due to release of renin as PRA decreased during infusion when normals were sodium loaded.…”

Section: Resultssupporting

confidence: 70%

“…However, P113 has been noted to cause a rise in blood pressure in some patients (Streeten et al, 1975), and these presumed agonist (Angiotensin II) effects of P113 have been observed in animal isolated tissues and in sodium loaded rabbits (Mimran, Hinrichs & Hollenberg, 1974). The agonist activity seeming to depend on the tissue studied, the endogenous level of angiotensin II and the sodium intake.…”

Section: Introductionmentioning

confidence: 99%

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Agonist and antagonist effects of Sar1‐ala8‐angiotensin II in salt‐ loaded and salt‐depleted normal man.

Macgregor¹,

Dawes²

1976

Brit J Clinical Pharma

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1 Three normal subjects were infused with Sarl -ala8 -angiotensin II (Saralasin, P1 13) whilst on a high sodium (200 mEq + normal diet) and a low sodium (10 mEq diet) intake. 2 On the high sodium intake when angiotensin II and plasma renin activity (PRA) were suppressed, P113 infusion (5-10 ,ug kg-' min-') caused a slight rise in BP and a marked drop in urine flow and sodium excretion, with a fall in glomerular filtration rate, and effective renal plasma flow. 3 On the low sodium intake, when angiotensin II and PRA were increased, P113 infusion (5-10 jig kg-' min-) caused no change in blood pressure, urine flow or sodium excretion. However, when PI 13 was infused at an incremental rate starting at 0.25 ,ug kg-' min-1 there was a fall in standing BP, which was maximal at an infusion rate of 1 ,ug kg-1 min-', and this fall in standing BP was largely abolished as the rate of infusion was increased to 10 Mg kg-1 min-. 4 These results show firstly that angiotensin II is involved in maintaining standing blood pressure during dietary sodium depletion in normal man and secondly that P113 does have agonist as well as antagonist activity in normal man, the effect depending on the level of angiotensin II and sodium intake. When looking for angiotensin II mediated hypertension it may be important to use an incremental rate of infusion of P1 13 as the agonist activity of larger doses may mask its hypotensive action.

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Section: Resultssupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Agonist and antagonist effects of Sar1‐ala8‐angiotensin II in salt‐ loaded and salt‐depleted normal man.

Macgregor¹,

Dawes²

1976

Brit J Clinical Pharma

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“…Classification of patients into low, normal, and high PRA subgroups was based On the concomitant 24-hour urine Na excretion as described by Laragh and colleagues. * 9 Upright PRA and PAC determinations on placebo and at 1 hour after the initial and effective doses of captopril were compared.…”

Section: Experimental Designmentioning

confidence: 99%

“…, ala']-angiotcnsin II (saralasin), has been effective in reducing BP in hypertensive patients but its clinical use has been limited by its partial agonistic properties and by the need for parenteral administration. 9 - 10 Recent evidence has suggested that substances that inhibit angiotensin II formation by blockade of angiotensin I converting enzyme may be clinically useful antihypertensive agents. 11 A nonapeptide, teprotide (SQ 20,881, BPF e .…”

mentioning

confidence: 99%

Acute and chronic effect of captropril in hypertensive patients.

Johns¹,

Baker²,

Ayers³

et al. 1980

Hypertension

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SUMMARY Acute and chronic antihypertenslve effects of the angiotensin conferring enzyme inhibitor, captoprii (SQ 14,225), was assessed in 29 consecutirely-studled patients with hypertension. (Mean arterial pressure, 110-160 mm Hg). Eighteen patients had essential hypertension (three with high plasma renln activity (PRA), 11 with normal PRA, four with low PRA); eight had renovascular hypertension (four with high PRA and four with normal PRA); two had end-stage renal parenchyma! disease, and one had primary aldosteronism due to bilateral adrenal hyperplasia. Antihypertensive drugs were discontinued approximately 1 month prior to being studied. Patients were studied on the metabolic unit and received a constant 100 mEq sodium and 60 mEq potassium/day diet Control data were obtained for 3 days with placebo treatment Captoprii was then begun at 10 or 25 mg and increased to a maximum of 100 or 150 mg four times per day. During die first 3-10 days of treatment, 16 patients (55%) achieved normal blood pressure (BP) on captoprii alone, and six patients (21%) achieved it with the addition of a diuretic Six patients (21%) exhibited a fall In diastoiic blood pressure (DBP) greater than 10 mm Hg, but did reach normal. Captoprii was ineffective in lowering BP in one patient (low PRA, essential hypertension). Of the 22 patients who achieved normal BP, all but one (normal PRA) exhibited a rise in PRA, and all exhibited a fall in plasma aldosterone concentration (PAC). Blood pressure, PRA, and PAC responses were independent of either etiologic classification or renln subtype. The mean effective daily dose of captoprii was 261 mg. Nineteen patients were followed from 1-18 months on maintenance captoprii therapy. Blood pressure remained well controlled, without evidence of toxldty, in all patients, although medication adjustment (either a dose increase or a diuretic) was required in all but five patients by the fifth outpatient month. The PRA remained elevated in 12 patients up to 6 months after discharge. The BP response was not predicted by control PRA, PAC, or BP, although there was a correlation between acute renin rise and BP reduction. These results indicate that captoprii is an effective, well-tolerated agent for the longterm treatment of hypertension of multiple etiologies. These results are consistent with captopril's known ability to block angiotensin II formation and perhaps to prevent bradyklnin degradation, although the primary mechanism responsible for BP reduction remains to be elucidated. A s S c i S r i S a " Established I n v e s t l « a t o r of the A m e n c a n H e a r t substrate has been reported with antirenin antibody/

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“…The first developed Ang I1 receptor antagonists were peptide analogs of Ang 11, e.g., saralasin (Sarl, Ala8-Ang 11) (40). These peptide antagonists were partial agonists and lacked oral bioavailability, however, and were not suitable for clinical use.…”

Section: Introductionmentioning

confidence: 99%