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To study the possible physiological role of atrial natriuretic peptide (ANP) in the regulation of intraocular pressure (IOP) the effects of an increase of endogenous ANP within the physiological range induced by the neutral endopeptidase 24.11 (NEP) inhibitor candoxatril were examined. In a single masked placebo controlled trial, seven patients were studied with normal IOP (six male, one female; average age 50 (range 37-62 years). Intraocular pressure in each eye was measured after 2 weeks of placebo, after 4 weeks of candoxatril 200 mg twice daily, and during the first 3 days of placebo washout. With 4 weeks of candoxatril, endogenous plasma ANP levels increased from 4-2 (SEM 1.5) to 6*0 (1.5) pmol/ I (p<004) and there was a significant decrease in mean arterial pressure from 119 (4) A role for atrial natriuretic peptide (ANP) in the regulation of intravascular fluid volume and blood pressure is now well established.I There is also preliminary evidence for pharmacological effects of ANP on the regulation of aqueous humour production and of intraocular pressure (IOP). Atrial natriuretic peptide has been identified in the anterior uvea in the rat,3 and specific receptors for ANP have been demonstrated in the pigmented epithelium of the ciliary processes in the rabbit.4 Intravenous or intravitreal injection of pharmacological doses of ANP cause a reduction in aqueous humour production and lower IOP in the rabbit.5-9 In primates, administration of ANP intravenously, or by injection into the anterior chamber of the eye, increases uveoscleral outflow.'0 Furthermore, acute intravenous injection of high dose ANP in patients with pathologically raised IOP reduced the intraocular pressure by around 15%." However, it is unclear whether ANP plays a physiological role in the regulation of IOP. Neutral endopeptidase (NEP) 24.11 inhibition is an important mechanism for the normal catabolism of ANP. We therefore examined the possible physiological effects of ANP in the eye by studying IOP during acute and chronic elevation of endogenous ANP within the normal range by the oral prodrug candoxatril which is metabolised to the NEP 24.11 inhibitor UK 73 967.12 Materials and methods We studied seven patients (six male, one female; average age 50 (range 37-62) years) with normal intraocular pressure (right eye 18 (SEM 1) mm Hg, range 11-22 mm Hg; left eye 17 (2) mm Hg, range 10-22 mm Hg) and average supine blood pressure 162/97

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Plasma atrial natriuretic peptide concentrations were measured by radioimmunoassay six to 77 weeks after operation in eight cardiac transplant recipients with no appreciable evidence of cardiac failure or rejection and in eight control subjects matched for age, sex, race, and blood pressure. Plasma atrial natriuretic peptide concentrations were significantly higher in the cardiac transplant recipients (mean 19-4 (SE 3.9) ng/l) than in the controls (7.3 (1-2) ng/l p

SUMMARY Plasma concentrations of atrial natriuretic peptide were measured in eight patients undergoing elective cardiac catheterisation and angiography. All patients had normal resting pressures in the cardiac chambers and no clinical evidence of heart failure. Plasma atrial natriuretic peptide rose significantly from the superior vena cava into the right atrium and right ventricle. The increase into the right atrium was variable, with no increase in three subjects, but there was a consistent increase in all subjects from the superior vena cava to the right ventricle. These findings in the right atrium are probably caused by inadequate mixing and streaming of blood from the coronary sinus containing high concentrations of atrial natriuretic peptide. There was no increase in the concentration of natriuretic peptide from the pulmonary artery to the left ventricle, but the concentrations in the left ventricle were significantly higher than in the superior vena cava.These findings demonstrate that the heart secretes atrial natriuretic peptides in the absence of cardiac failure. Studies based on sampling of the right atrium will not accurately measure cardiac secretion of atrial natriuretic peptide and will therefore be likely to obscure the mechanisms responsible for regulating its secretion. The right ventricle and pulmonary artery are the best sampling sites to measure atrial natriuretic peptide release from the right atrium.There is increasing evidence that atrial natriuretic peptide may be important in the regulation of salt and water balance. We measured plasma concentrations of atrial natriuretic peptide in blood samples taken from a peripheral vein, the superior vena cava, and in the chambers of the heart during routine cardiac catheterisation and coronary angiography in patients who had possible ischaemic heart disease but normal cardiac pressures. Patients and methodsThe eight white patients (five men and three women; mean age 60 5 years, range 54-67) studied were