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Background: The purpose of this study was to determine the preoperative clinical and biological factors that predict the clinical outcomes after surgery, in subjects with aldosterone-producing adenomas (APAs)., Methods: Fifty-eight patients (mean age 52 +/- 11 years) with APA were followed up for 43 +/- 13 months after they had undergone unilateral adrenalectomy. The subjects were classified as "cured" (n = 23) if the blood pressure (BP) was <140/90 mm Hg without postoperative medication, "normalized" (n = 20) if BP was <140/90 mm Hg with antihypertensive therapy, and "uncontrolled" (n = 15) if a BP of < or =140/90 mm Hg was not achieved despite intensive therapy., Results: The cured patients had a significantly lower mean preoperative age, cardiac mass, and serum creatinine (P < 0.001) than the other subjects. The main independent predictors of surgical curability were: age (P < 0.01), low serum potassium (P < 0.0001), and the urinary aldosterone-to-active-renin (UAAR) ratio (P < 0.008). Among the hormonal parameters, the UAAR ratio provided the best area under the receiver operating-characteristics curve (0.802 (confidence interval (CI) 95%: 0.676-0.944)). For a cutoff value of 15, the positive and negative predictive values of the UAAR ratio were 85 and 92%, respectively. In the study population as a whole, surgical treatment restored the age-systolic BP (SBP) relationship (P < 0.006), which was insignificant before surgery., Conclusions: Although all the subjects showed lowering of BP after surgery, and the age-BP relationship was restored, the long-term cure rate of APA subjects was 40%. The UAAR ratio, by comparison with other classical hormonal features of primary aldosteronism, was the best independent predictor of the cure of hypertension after adrenalectomy.

Sodium (Na) excretion is to an extent tied to calcium (Ca) excretion; increases in Ca result in increased Na excretion. We hypothesized that molecular variation in the calcium-sensing receptor (CaSR), which imparts certain of the influences of extracellular Ca, might be related to differences in Na balance and blood pressure. We further hypothesized that such an influence by CaSR is more pronounced in blacks than in whites, as the hypertension in blacks appears to be more dependent on Na retention. Three common molecular variants in CaSR were studied. Two were more frequent in the whites (A986S, P < .0001, and G990R, P = .093), whereas Q1011E was more frequent in the blacks (P < .0001). Two distinctly separate groups were studied: (1) healthy schoolchildren in whom levels of the renin-aldosterone axis and blood pressure were measured, and (2) normotensive and hypertensive adults. Studies of association were made separately in the whites and the blacks. No association of any of the variants with Na balance (as estimated from renin and aldosterone levels) was observed. In the black schoolchildren, Q1011E showed a marginal association with a higher blood pressure (P = .093 for systolic and P = .025 for diastolic), a relationship that was considered to be nonsignificant after adjusting for multiple comparisons. Nor was there a significant association of the variants with presence or absence of hypertension. In summary, studies of two cohorts that included whites and blacks did not suggest that molecular variations in the CaSR influence either Na balance or blood pressure.

Dextrorotatory (+) and levorotatory (-) ozolinone (ozo) were injected directly into the left renal artery of volume-expanded anesthetized dogs. (+)Ozo (40 micrograms/kg/min) had no effect on urine flow and fractional excretion of Na+, Cl-, or K+ when compared with the basal period. Comparison of (-)ozo to (+)ozo revealed the following: urine flow 4.0 +/- 0.3 v 0.9 +/- 0.1 mL/min (P < .001); FENa+ 29.8 +/- 3.0 v 5.6 +/- 0.3% (P < .001); FECl- 35.7 +/- 4.1 v 5.8 +/- 0.4% (P < .001); FEK+ 87 +/- 4 v 49 +/- 5% (P < .001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) did not change. The renin secretory rate (RSR) was significantly higher with (-)ozo than with (+)ozo (498 +/- 113 v 210 +/- 53 ng A I/mL/hr.mL/min). Moreover, (-)ozo significantly increased urine PG excretion compared to basal values: 466 +/- 63 v 263 +/- 30 pg/min (P < .05). Indomethacin (2 mg/kg) markedly blunted the effects of (-)ozo on PG and RSR, and completely abolished the rise in PRA. (+)Ozo had no significant effect on urine PG excretion. Neither (-)ozo nor (+)ozo had an effect on renin production in isolated glomeruli. By contrast, (-)ozo but not (+)ozo increased PGE2 synthesis in papillary and medullary slices. The data are consistent with the proposal that the effect of (-)ozo on renin secretion and PRA is through a PG-dependent mechanism, and that it requires an intact macula densa mechanism.

A low dose of dopamine (1 microgram/min/kg) infused for 3 h, which is without systemic hemodynamic effects in normal subjects, increased the renal blood flow and renal production of prostacyclin (PGI2). This action was blocked by metoclopramide as well as by either of two cyclooxygenase (CO) blockers, but effects were not altered by administration of the alpha 1 blocker prazosin. Much of the effect of dopamine (DA) is apparently via the DA1 receptor, since fenoldopam (0.1 microgram/min/kg) reproduced these actions. However, although fenoldopam increased glomerular filtration rate and urinary Na+, CO blockers were without effect. In contrast neither DA or fenoldopam infusions changed either renal blood flow or PGI2 in a group of patients with essential hypertension. Renin secretion was shown to be increased via DA1 receptor activation both in humans and rat renal tissue. The DA2 receptor may also play a role since domperidone can reduce renal blood flow.