Evidence of prostacyclin deficiency in the syndrome of hyporeninemic hypoaldosteronism.
Hyporeninemic hypoaldosteronism is an important cause of hyperkalemia and is characterized by low renin secretion. We found that prostacyclin, a potent vasodilator and renin secretagogue, was markedly reduced--as reflected by its stable urinary metabolite 6-keto-prostaglandin F1 alpha--in seven patients with hyporeninemic hypoaldosteronism as compared with seven matched controls with renal insufficiency and as compared with 12 normal volunteers (mean +/- SE, 42 +/- 7 vs. 185 +/- 37 and 164 +/- 20 ng per gram of creatinine, respectively; P less than 0.001). In contrast, renal prostaglandin E2 excretion was similar in all three groups. A low-dose infusion of calcium or norepinephrine (known stimulants of prostacyclin) increased renal prostacyclin release in normal subjects and controls with renal insufficiency. Neither agonist, however, increased the low basal prostacyclin excretion in the patients (49.6 +/- 11 [basal] vs. 62 +/- 20 [norepinephrine] and 47.5 +/- 16 [calcium]; P greater than 0.8). To evaluate the functional importance of the altered prostacyclin production, we studied the responses of renal blood flow and blood pressure to the calcium infusion. The calcium infusion did not alter blood pressure or renal blood flow in the normal subjects or the controls with renal insufficiency. In contrast, the same dose of calcium in the patients with hyporeninemic hypoaldosteronism produced a rise in mean blood pressure (from 91 +/- 6 to 104 +/- 8 mm Hg, P less than 0.05) and a fall in renal blood flow (from 673 +/- 58 to 560 +/- 42 ml per minute per 1.73 m2, P less than 0.05). These results indicate that a deficiency of prostacyclin could explain the low active-renin concentration and altered vasomotor tone seen in hyporeninemic hypoaldosteronism.
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis / Q000172:deficiency* / Q000502:physiology; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000652:urine; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood* / Q000172:deficiency; D013577:Syndrome; D014666:Vasomotor System / Q000502:physiology
D000450:Aldosterone; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D012083:Renin; D002118:Calcium; D009638:Norepinephrine