Koreaki Baba

Inhibition of Aldosterone Production by Adrenomedullin, a Hypotensive Peptide, in the Rat

Recently, we conducted in vitro studies and reported that adrenomedullin, a novel hypotensive peptide, inhibits aldosterone secretion by dispersed rat adrenal zona glomerulosa cells. To assess the physiological role of this inhibitory effect, we investigated the effect of adrenomedullin on aldosterone production in vivo. Male Sprague-Dawley rats were fed a normal sodium diet before the experiments. To begin the experimental procedure, we stimulated aldosterone production with a sodium-deficient diet or bilateral nephrectomy. After 3 days of sodium depletion or immediately after nephrectomy, we injected synthetic human adrenomedullin (2.5 nmol/kg SC) and repeated the injection three times at 6-hour intervals. Two hours after the last injection, the rats were decapitated and adrenal capsular tissue was collected. Adrenomedullin had no effect on plasma and adrenal aldosterone concentrations in the rats fed a normal sodium diet. Rats fed a sodium-deficient diet had significantly increased aldosterone concentrations in both plasma (4770.1 +/- 364.3 pmol/L) and adrenal gland (57.34 +/- 3.27 pmol per adrenal). Subsequently, injection of adrenomedullin significantly inhibited increases in concentrations (plasma, 2648.9 +/- 313.2 pmol/L; adrenal, 44.28 +/- 4.94 pmol per adrenal). In nephrectomized rats, increased aldosterone concentrations in plasma and adrenal gland were also significantly inhibited by adrenomedullin. In the second part of the study, plasma renin concentration, adrenal renin activity, plasma corticosterone concentration, serum potassium concentration, and plasma immunoreactive adrenomedullin concentration were examined for adrenomedullin effects. The first four were unaffected, and the last, plasma immunoreactive adrenomedullin, was elevated 15% to 30%. These in vivo results, together with our in vitro data, suggest that adrenomedullin may indeed play a physiological role in the control of blood pressure and electrolyte balance.

Effect of Propranolol and Indomethacin on the Depressor Action of Captopril in Patients with Essential Hypertension

The contribution of the renin-angiotensin system (RA) and of prostaglandins (PG) to the acute depressor effect of captopril (Capt) was studied in 13 hypertensive patients suppressing either RA by propranolol (Prop) or PG by indomethacin (Indo). Four patients showed abolition of the depressor effect of Capt by pretreatment with both Prop and Indo (Group 1). Indo, but not Prop, cancelled the depressor effect in another 4 patients (Group 2). In the remaining 5 patients, either Prop or Indo did not alter the depressor response to Capt (Group 3). Patients in Group 3 were older than patients in Group 1 and 2 and showed lower plasma volume value. Several mechanisms might contribute to the acute depressor effect of Cap, including not only the suppression of RA and the enhancement of PG, but perhaps other undetermined factor(s), especially in older patients.

Changes in total body potassium during long-term thiazide treatment: Effects of potassium supplements on total body and serum potassium in hypertensive patients with thiazide treatment

To evaluate the effects of long-term treatment with diuretics on potassium metabolism in hypertensive patients, serum potassium (serum K) and total body potassium (TBK) were determined in 66 hypertensive patients receiving long-term trichlormethiazide therapy and in 42 hypertensive control patients receiving no medication. No significant change in serum K was observed during sixty months of thiazide therapy. Serum K was, however, decreased significantly in patients receiving thiazides for more than 60 months. TBK did not change significantly during the first 24 months of thiazide therapy, but it significantly decreased at 24 to 60 months of thiazide treatment (P<0.01).The effects of potassium supplementation on serum K and TBK during thiazide treatment were studied prospectively in 6 hypertensive patients. Serum K and TBK did not change by the administration of potassium chloride (16–24 mEq/day) and potassium gluconate (16–24 mEq/day), but spironolactone (75 mg/day) increased serum K and TBK during thiazide treatment (p<0.05).