For high-risk groups of hypertensive patients and those with hypokalemia, we recommend case detection of primary aldosteronism by determining the aldosterone-renin ratio under standard conditions and recommend that a commonly used confirmatory test should confirm/exclude the condition. We recommend that all patients with primary aldosteronism undergo adrenal computed tomography as the initial study in subtype testing and to exclude adrenocortical carcinoma. We recommend that an experienced radiologist should establish/exclude unilateral primary aldosteronism using bilateral adrenal venous sampling, and if confirmed, this should optimally be treated by laparoscopic adrenalectomy. We recommend that patients with bilateral adrenal hyperplasia or those unsuitable for surgery should be treated primarily with a mineralocorticoid receptor antagonist.

We recommend case detection of primary aldosteronism be sought in higher risk groups of hypertensive patients and those with hypokalemia by determining the aldosterone-renin ratio under standard conditions and that the condition be confirmed/excluded by one of four commonly used confirmatory tests. We recommend that all patients with primary aldosteronism undergo adrenal computed tomography as the initial study in subtype testing and to exclude adrenocortical carcinoma. We recommend the presence of a unilateral form of primary aldosteronism should be established/excluded by bilateral adrenal venous sampling by an experienced radiologist and, where present, optimally treated by laparoscopic adrenalectomy. We recommend that patients with bilateral adrenal hyperplasia, or those unsuitable for surgery, optimally be treated medically by mineralocorticoid receptor antagonists.

Background-Although unilateral primary aldosteronism is the most common surgically correctable cause of hypertension there are no standard criteria to classify surgical outcomes.

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Uninephrectomized rats drinking 1% sodium chloride were given aldosterone (Aldo, 0.75 gg/h, subcutaneous Is.c.I infusion), deoxycorticosterone (DOC, 20 mg/wk, s.c.), corticosterone (B, 2 mg/d, s.c.), or the antiglucocorticoid-antiprogestin RU486 (2 mg/d, s.c.) for 8 wk, and hemodynamic and tissue responses were compared with a non-steroid-treated control group. Aldo and DOC markedly increased systolic BP and caused considerable (40-50%) cardiac hypertrophy; B and RU486 caused neither hypertension nor cardiac hypertrophy. Measurements of ventricular cross-sectional areas showed hypertrophy due to an increase in mass of the left ventricle only. Cardiac hydroxyproline concentration was increased considerably by Aldo and DOC, to a lesser degree by RU486, and not by B. Aldo markedly elevated left ventricular interstitial collagen (2.5-fold vs control, P < 0.01 vs all groups); other steroid treatments also increased interstitial collagen over control (DOC X 1.8-, RU486 X 1.6-, B X 13-fold), with identical responses for right and left ventricles (r = 0.94). A different pattern of perivascular fibrosis was noted; DOC elevated perivascular collagen (2.1-fold vs control, P < 0.01 vs all other groups); RU486 raised levels 1.4-fold vs control, but neither Aldo nor B significantly affected perivascular collagen. These data are consistent with interstitial cardiac fibrosis reflecting type I (mineralocorticoid) receptor occupancy by administered Aldo or DOC, or by elevated endogenous B after type II (glucocorticoid) receptor blockade after RU486 administration; perivascular fibrosis may reflect a composite response after type I receptor agonist/type II glucocorticoid receptor antagonist occupancy. (J. Clin. Invest. 1994.93:2578-2583

Abstract-Increased mineralocorticoid levels plus high salt promote vascular inflammation and cardiac tissue remodeling.Mineralocorticoid receptors are expressed in many cell types of the cardiovascular system, including monocytes/macrophages and other inflammatory cell types. Although mineralocorticoid receptors are expressed in monocytes/macrophages, their role in regulating macrophage function to date has not been investigated. We, thus, used the Cre/LoxP-recombination system to selectively delete mineralocorticoid receptors from monocytes/macrophages with the lysozyme M promoter used to drive Cre expression (MR flox/flox /LysM Cre/Ϫ mice). Male mice from each genotype (MR flox/flox or wild-type and MR flox/flox /LysM Cre/Ϫ mice) were uninephrectomized, given 0.9% NaCl solution to drink, and treated for 8 days or 8 weeks with either vehicle (nϭ10) or deoxycorticosterone (nϭ10). Equivalent tissue macrophage numbers were seen for deoxycorticosterone treatment of each genotype at 8 days; in contrast, plasminogen activator inhibitor type 1 and NAD(P)H oxidase subunit 2 levels were increased in wild-type but not in MR flox/flox / LysM Cre/Ϫ mice given deoxycorticosterone. Baseline expression of other inflammatory genes was reduced in MR flox/flox /LysM Cre/Ϫ mice compared with wild-type mice. At 8 weeks, deoxycorticosterone-induced macrophage recruitment and connective tissue growth factor and plasminogen activator inhibitor type 1 mRNA levels were similar for each genotype; in contrast, MR flox/flox /LysMCre/Ϫ mice showed no increase in cardiac fibrosis or blood pressure, as was seen in wild-type mice at 8 weeks. These data demonstrate the following points: (1) mineralocorticoid receptor signaling regulates basal monocyte/macrophage function; (2) macrophage recruitment is not altered by loss of mineralocorticoid receptor signaling in these cells; and (3) a novel and significant role is seen for macrophage signaling in the regulation of cardiac remodeling and systolic blood pressure in the deoxycorticosterone/salt model. T he clinical use of mineralocorticoid receptor (MR) antagonists added to the current standard of care reduces morbidity and mortality in patients with congestive heart failure 1,2 and reduces blood pressure and proteinuria as monotherapy in essential hypertension. 3 Although the precise mechanism for this protection remains to be determined, considerable insights have been obtained from experimental models of mineralocorticoid/salt-mediated cardiac fibrosis 4 -6 ; hypertension, cardiac hypertrophy, and fibrosis are key responses to the administration of aldosterone or deoxycorticosterone (DOC) concurrently with a high salt intake for 8 weeks. Importantly, the pathogenesis of cardiac fibrosis is independent of hypertension and cardiac hypertrophy in this model, suggesting a direct role for MR activation in driving the onset and progression of cardiovascular disease. 4 -6 We and others have previously identified vascular inflammation (ie, osteopontin and plasminogen activator inhibitor type 1 [PA...

authors request that the following corrections be noted.In this paper, a calculation was presented of tdc, a mean capture time for those low density lipoprotein (LDL) receptors trapped by a coated pit during the lifetime of the coated pit. However, the appropriate mean capture time for this problem must also take into account LDL receptors that are not captured during any single lifetime of a coated pit. When this is done, the mean capture time becomeswhere f is the fraction of LDL receptors trapped during the lifetime of a coated pit. The fractionf is given by the expression f r(bv 2 1 r(r)dr= (b2 2al where a = \/K72 and v(r), E1, and A10 are given in the Appendix of the paper. Corrections