The relation of arterial pressure and plasma angiotensin II concentration. A change produced by prolonged infusion of angiotensin II in the conscious dog.
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Biomedical subjects
Publications and source records attributed to A F Lever.
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1. Total-body neutron-activation analysis in vivo was carried out in 11 hypertensive subjects to measure simultaneously the total body content of sodium, chlorine, calcium, phosphorus and nitrogen. 2. There was a highly significant correlation between total body sodium measured by activation analysis and total exchangeable sodium measured by a standard isotope-dilution technique (r = 0.92, P less than 0.001). Exchangeable sodium averaged 80.3% of total body sodium. 3. The measured values of chlorine, calcium, phosphorus and nitrogen were similar to those for healthy subjects reported by others. 4. Activation analysis in vivo appears promising as an additional tool for investigating sodium metabolism in hypertension, as it is the only method available for determining the total body content of this element. The radiation dose (1 rem) is sufficiently low to permit repeated measurements in the same subject.
1. A patient presented with mild hypertension, a raised plasma total renin concentration but a normal plasma angiotensin II concentration. The discrepancy was due to a high concentration of inactive renin in the plasma. 2. A renal carcinoma was detected and removed. The tumour contained a higher proportion of inactive renin than was found in uninvolved areas of the kidney. After unilateral nephrectomy, the plasma concentration of inactive renin fell to normal. 3. Six months later, plasma inactive renin concentration again increased and a metastasis was detected in a rib. Excision of the rib together with radiotherapy resulted in a fall in plasma inactive renin to normal. 4. The inactive renin in plasma and tumour extracts was activated to the same extent by acid treatment and by trypsin.
1. Infusion of angiotensin II into dogs at constant dose over 2 weeks caused a progressive rise in arterial pressure. 2. When the infusion was stopped the pressure dropped slowly from hypertensive levels over 48 h. 3. Dose-response studies at weekly intervals showed progressive elevation, without steepening, of the plasma angiotensin II-blood pressure curve. 4. Thus, during prolonged administration of angiotensin II, a given plasma concentration of the peptide can sustain a higher arterial pressure than it can during acute infusions.
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The possibility that the responsiveness of plasma aldosterone concentration to angiotensin II alters with changes in sodium balance was investigated in male beagle dogs under conditions of controlled sodium and potassium intake. Angiotensin II was infused at four different rates (usually 3, 6, 12, and 24 ng/kg/min), each for 1 h, 1) after periods of normal sodium diet (32 mEq/day), 2) after moderate sodium depletion (negative cumulative sodium balance 25-58 mEq), 3) after severe sodium depletion (65-116 mEq negative cumulative sodium balance), and 4) after sodium loading (150-212 mEq positive sodium balance), daily potassium intake remaining constant (26 mEq/day) throughout. Angiotensin II/aldosterone dose-response curves after moderate sodium depletion were both elevated and steepened in comparison with those found during normal sodium intake. Severe sodium depletion was associated with even greater elevation of dose-response curves, but individual aldosterone responses to angiotensin II were irregular and unpredictable. Sodium loading significantly diminished aldosterone responsiveness to angiotensin II. Blood pressure increments during angiotensin II infusion were attenuated by sodium depletion.
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1. Amiloride (40 mg/day) was given to nineteen patients with primary hyperaldosteronism. There were significant falls in systolic and diastolic blood pressure, in total exchangeable sodium and in serum sodium and bicarbonate, while total exchangeable potassium, total body potassium, serum potassium, chloride and urea, plasma renin, angiotensin II and aldosterone all increased significantly. Amiloride was effective in reducing the blood pressure in patients with and without adrenocortical adenoma. No carry-over effect was seen on withdrawing amiloride. Similar changes were associated with amiloride treatment in five patients with essential hypertension; hyperkalaemia was not observed. 2. Only negligible side effects were encountered in the entire series of 24 patients.
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Amiloride (40 mg/day) was given to nineteen patients with primary hyperaldosteronism. There were significant falls in systolic and diastolic blood pressure, in total exchangeable sodium, and in serum sodium sodium and bicarbonate; while total exchangeable potassium, total body potassium, serum potassium, chloride and urea, and plasma renin, angiotensin II and aldosterone all increased significantly. Amiloride was effective in reducing blood pressure in patients with and without adrenocortical adenoma. No carry-over effect was seen on withdrawing amiloride. Similar changes were associated with amiloride treatment in five patients with essential hypertension; hyperkalaemia was not observed. Only negligible side-effects were encountered in the entire series of twenty-four patients.
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