Therapeutic use of atrial natriuretic factor.

Connell, John; Jardine, Alan G.; Northridge, David B.

doi:10.1111/j.1365-2125.1992.tb04117.x

Cited by 3 publications

(5 citation statements)

References 36 publications

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“…This has exciting potential where there is a dynamic component to pulmonary vasoconstriction as may be seen in cor pulmonale. Despite showing initial promise in the treatment of CHF [67], the use of NEP inhibitors appears to be losing favour [4]. The above evidence suggests that these agents may be more effective in conditions like cor pulmonale, where their vasorelaxant properties may translate into clinical benefits for such patients.…”

Section: Therapeutic Relevancementioning

confidence: 99%

“…vascular tone. The diverse origins, structure and Indeed, therapeutic innovation in the manipulation of effects of these peptides have so far defeated attempts vasoactive peptides has led to important advances in to determine fully their relative importance as well as the management of these conditions [3,4], with There is however increasing evidence that vasoactive peptides are also important as modulators of the pulmonary vascular bed. This review will discuss the pulmonary haemodynamic effects of the vasoactive peptides which form part of the reninangiotensin system (RAS), in particular angiotensin II, and the natriuretic peptide system (NPS).…”

Section: Introductionmentioning

confidence: 99%

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The role of the renin‐angiotensin and natriuretic peptide systems in the pulmonary vasculature.

Cargill

Lipworth

1995

Brit J Clinical Pharma

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1 The role of vasoactive peptide systems in the pulmonary vasculature has been studied much less extensively than systemic vascular and endocrine effects. The current understanding of the role of the renin-angiotensin (RAS) and natriuretic peptide systems (NPS) in the pulmonary ciruclation is therefore reviewed. 2 Plasma concentrations of angiotensin II, the main vasoactive component of the RAS, are elevated in pulmonary hypertension and may interact with hypoxaemia to cause further pulmonary vasoconstriction. Pharmacological manipulation of angiotensin II can attenuate hypoxic pulmonary vasoconstriction but larger studies are needed to establish the efficacy of this therapeutic strategy in established pulmonary hypertension. 3 Although all the known natriuretic peptides, ANP, BNP and CNP are elevated in cor pulmonale, only ANP and BNP appear to have pulmonary vasorelaxant activity in humans. ANP and BNP can also attenuate hypoxic pulmonary vasoconstriction, suggesting a possible counter-regulatory role for these peptides. Inhibition of ANP/BNP metabolism by neutral endopeptidase has been shown to attenuate development of hypoxic pulmonary hypertension but this property has not been tested in humans. 4 It is also well established that there are potentially important endocrine and systemic circulatory interactions between the RAS and NPS. This also occurs in the pulmonary circulation and in humans, where at least BNP acts to attenuate angiotensin II induced pulmonary vasoconstriction. This interaction may be particularly relevant as a mechanism to counter-regulate overactivity of the RAS. 5 Although the NPS and RAS have profound effects on the pulmonary circulation, the therapeutic potential of manipulating these systems has yet to be realised.

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Section: Therapeutic Relevancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of the renin‐angiotensin and natriuretic peptide systems in the pulmonary vasculature.

Cargill

Lipworth

1995

Brit J Clinical Pharma

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“…There is now considerable evidence to suggest that ANP represents a new and important component of the integrated control of cardiovascular homeostasis, and sodium balance in particular [ 1-31, With the availability of alpha-ANP for administration in humans, several studies have already been carried out to investigate the possible therapeutic potential of ANP in various conditions, including congestive heart failure as well as essential hypertension [4,5].…”

Section: Introductionmentioning

confidence: 99%

Hormonal and renal responses to neutral endopeptidase inhibition in normal humans on a low and on a high sodium intake

Sagnella¹,

Markandu²,

Buckley³

et al. 1995

Eur J Clin Investigation

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Hormonal and renal effects of candoxatril, a neutral endopeptidase 24.11 inhibitor, were investigated in eight subjects equilibrated on a low sodium diet (10 mmol sodium per day) and a high sodium (350 mmol per day) diet. After candoxatril treatment, plasma ANP increased to a maximum at 2-4 h and declined to baseline within 24 h. The increases were relatively greater on the high sodium diet, which was also associated with increases in urinary sodium, with highest values at 4h. On the low sodium diet, the magnitude of the changes was significantly lower (24 h cumulative sodium excretion was 11.4 +/- 5.5 mmol on the low sodium diet and 73.1 +/- 25.6 mmol on the high sodium diet; P < 0.01). There were no significant effects on urinary potassium excretion, creatinine clearance or haematocrit. After candoxatril treatment there were reductions in PRA, especially on the low sodium diet. On either diet there were no effects on systemic blood pressure. These results demonstrate that dietary sodium intake is an important determinant of the renal and hormonal responses to neutral endopeptidase inhibition.

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“…154 The acute intravenous injection of ANF (100 µg) reduced the IOP of glaucoma patients for more than 8 h. 155 ANF is metabolically degraded by neutral endopeptidase, and inactivation of the latter can prolong the biological availability of ANF. 156 Oral dosing for 4 weeks with the neutral endopeptidase inhibitor, candoxatril, resulted in a reduction in the IOP of ocular normotensive individuals, an effect that was positively correlated with increases in plasma ANF levels and not with changes in systemic blood pressure. 157 Like ANF, nitrovasodi- lators such as nitroglycerin stimulate guanylate cyclase via the production of nitric oxide, and the acute topical administration of agents such as nitroglycerin, hydralazine, and sodium nitroprusside can lower the IOP of rabbits, an effect associated with an increase in aqueous humor outflow.…”

Section: Guanylate Cyclase Activatorsmentioning

confidence: 98%

“…The acute intravenous injection of ANF (100 μg) reduced the IOP of glaucoma patients for more than 8 h . ANF is metabolically degraded by neutral endopeptidase, and inactivation of the latter can prolong the biological availability of ANF . Oral dosing for 4 weeks with the neutral endopeptidase inhibitor, candoxatril, resulted in a reduction in the IOP of ocular normotensive individuals, an effect that was positively correlated with increases in plasma ANF levels and not with changes in systemic blood pressure .…”

Section: Guanylate Cyclase Activatorsmentioning

confidence: 99%

New Approaches to Antiglaucoma Therapy

Sugrue

1997

J. Med. Chem.

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Therapeutic use of atrial natriuretic factor.

Cited by 3 publications

References 36 publications

The role of the renin‐angiotensin and natriuretic peptide systems in the pulmonary vasculature.

The role of the renin‐angiotensin and natriuretic peptide systems in the pulmonary vasculature.

Hormonal and renal responses to neutral endopeptidase inhibition in normal humans on a low and on a high sodium intake

New Approaches to Antiglaucoma Therapy

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