1980 Volume 27 Issue 4 Pages 417-429
In two patients with Bartter's syndrome, significant increases in serum immunoreactive prostaglandin E like-material (iPGE) and urinary kallikrein excretion were observed during the control period. Urinary PGE excretion was not always increased as serum iPGE. After an administration of indomethacin, an inhibitor of prostaglandins (PG's) synthetase, their clinical symptoms, hyperactivity of renin-angiotensinaldosterone (R-A-A) system and resistence to the pressor effects of angiotensin II and norepinephrine were apparently eliminated, but hypokalemia was not corrected completely. Indomethacin caused a remarkable decline in urinary kallikrein excretion and in serum and urinary PG's values. Spironolactone also produced a significant fall in urinary kallikrein excretion in spite of an extreme increase in the R-A-A system activity. However, spironolactone did not suppress the urinary PGE excretion. After an administration of aminoglutethimide, the urinary kallikrein excretion decreased gradually, followed by a decline in aldosterone production.Short-term administration of aspirin, ibuprofen, aminoglutethimide and dexamethasone did not improve hypokalemia despite the normalization of aldosterone production.
An angiotensin II antagonist, [Sar1, Ile8] angiotensin II, lowered the blood pressure of hyperreninemic patients. After indomethacin, a significant improvement in blood pressure response to this antagonist was observed. These results indicate that angiotenin II receptors of arteriolar smooth muscle in patients with Bartter's syndrome are still responsive to endogenous angiotensin II, andthat the R-A-A system plays a considerable role in the regulation of blood pressure. Moreover, our observations suggest that a more “proximal” cause of Bartter's syndrome is renal potassium wasting i. e., hypokalemia which causes an inappropriate production of PG's in the kidney and vascular walls, resulting in vasocontrictor insensitivity and hyperactivity of the R-A-A system. Likewise, it appears that hyperactivity of the renal kallikrein-kinin system does not stimulate the production of PG's in this syndrome, but rather is secondary to increased PG's synthesis
