Hemodynamic and hormonal responses during captopril therapy for heart failure: acute, chronic and withdrawal studies.

The hemodynamic and hormonal responses to acute and chronic captopril therapy and to its temporary withdrawal were studied in seven patients with congestive heart failure. Maximal hemodynamic and hormonal effects were reached with 25 to 50 mg doses of captopril. Since plasma angiotensin II levels were significantly higher 6 1/2 hours than 1 hour after administration of captopril, the drug should be given not less often than three times daily. No evidence of hormonal "escape" during long-term (mean 4 1/2 months) captopril therapy was observed, and initial hemodynamic responses were well maintained. Cessation of captopril administration resulted in abrupt increases in circulating angiotensin II levels, in arterial pressure, and in both pulse rate and plasma norepinephrine, but no decrease in cardiac function in the short-term was detected.

Nocturnal cortisol release during hypoglycemia in diabetes.

Nocturnal hypoglycemia in insulin-treated diabetic persons is often difficult to recognize clinically. It has been suggested that a useful biochemical test to demonstrate this would be the increased excretion of cortisol in the urine during the overnight period. However, of six diabetic persons who had nocturnal hypoglycemia (less than or equal to 2.5 mmol/L), plasma cortisol profiles and overnight urinary cortisol-creatinine ratios were abnormal in only one. In four others the plasma cortisol levels and cortisol excretion indices were indistinguishable from either a normal control group or a group of five diabetic subjects who did not develop nocturnal hypoglycemia. The remaining patient had a raised urinary cortisol-creatinine ratio, but did not show increased plasma levels of cortisol, growth hormone, or glucagon during the hypoglycemic phase. These data do not support the usefulness of the urinary cortisol-creatinine index as a marker of nocturnal hypoglycemia in diabetes.

Angiotensin II is more potent than potassium in regulating aldosterone in cardiac failure: evidence during captopril therapy.

Potassium and angiotensin II are major regulators of aldosterone secretion. To assess which of these stimuli is the more potent, we measured aldosterone, potassium, and angiotensin II responses to the oral converting enzyme inhibitor captopril in five patients with resistant congestive heart failure during digoxin and furosemide maintenance therapy. In spite of a positive cumulative potassium balance and a clear-cut rise in plasma potassium, aldosterone levels in plasma and urine declined in parallel with levels of angiotensin II. When captopril treatment was later withdrawn in three patients, angiotensin II and aldosterone levels increased in parallel, while plasma potassium remained steady. The results show that under these study conditions, angiotensin II is more potent than potassium in regulating aldosterone in patients with heart failure.

An isolation system for aldosterone and tetrahydroaldosterone prior to estimation by gas liquid chromatography or radioimmunoassay.

We report a method of isolation of aldosterone and tetrahydroaldosterone from urine and undiluted plasma which is based on extraction with Amberlite XAD-2 resin and purification by low pressure liquid chromatography using microbore LH-20 columns. Thin-layer chromatography on polyamide plates is introduced as the final step of a procedure designed to reduce destruction of steroids to a minimum, and to provide, in addition, a facility for multisample processing. Using a synthetic substrate, it has been shown that enzyme hydrolysis of steroid conjugates is possible whilst still adsorbed to the resin after extraction although the yield is lower than when hydrolysis is performed in solution.