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PubMed2006

Increased renal alpha-ENaC and NCC abundance and elevated blood pressure are independent of hyperaldosteronism in vasopressin escape.

Previously, we demonstrated that rats undergoing vasopressin escape had increased mean arterial blood pressure (MAP), plasma and urine aldosterone, and increased renal protein abundance of the alpha-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of gamma-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA. Am J Physiol Renal Physiol 287: F1076-F1083, 2004; Ecelbarger CA, Knepper MA, and Verbalis JG. J Am Soc Nephrol 12: 207-217, 2001). Here, we determine whether changes in these renal proteins and MAP require elevated aldosterone levels. We performed adrenalectomies (ADX) or sham surgeries on male Sprague-Dawley rats. Corticosterone and aldosterone were replaced to clamp these hormone levels. MAP was monitored by radiotelemetry. Rats were infused with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) via osmotic minipumps (5 ng/h). At day 3 of dDAVP infusion, seven rats in each group were offered a liquid diet [water load (WL)] or continued on a solid diet (SD). Plasma aldosterone and corticosterone and urine aldosterone were increased by WL in sham rats. ADX-WL rats escaped, as assessed by early natriuresis followed by diuresis; however, urine volume and natriuresis were somewhat blunted. WL did not reduce the abundance or activity of 11-beta-hydroxsteroid dehydrogenase type 2. Furthermore, the previously observed increase in renal aldosterone-sensitive proteins and escape-associated increased MAP persisted in clamped rats. The densitometry of immunoblots for NCC, alpha- and gamma-70 kDa ENaC, respectively, were (% sham-SD): sham-WL, 159, 278, 233; ADX-SD, 69, 212, 171; ADX-WL, 116, 302, 161. However, clamping corticosteroids blunted the rise at least for NCC and gamma-ENaC (70 kDa). Overall, the increase in aldosterone observed in vasopressin escape is not necessary for the increased expression of NCC, alpha- or gamma-ENaC or increased MAP associated with "escape."

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed1985

Mineralocorticoid and glucocorticoid receptors in circulating mononuclear leukocytes of patients with primary hyperaldosteronism.

Mineralocorticoid and glucocorticoid receptors were measured in circulating mononuclear leukocytes in 5 patients affected by Conn's syndrome (3 cases of bilateral adrenal hyperplasia and 2 cases of adenoma plus unilateral hyperplasia). The number of the binding sites per cell resulted significantly lower (189 +/- 114, mean +/- SD), as compared with the normal controls (298 +/- 105). The affinity of aldosterone for the receptor was found to be not different than that of healthy control subjects. The capacity and the affinity of dexamethasone for glucocorticoid receptors ranged in the normal values. These data suggest a possible down-regulation of mineralocorticoid receptors in humans.

Adenoma↗
PubMed1985

21-Deoxytetrahydroaldosterone excretion in primary hyperaldosteronism.

In earlier studies by our group it was shown that the urinary tetrahydroaldosterone excretion is a more reliable test for the diagnosis of primary aldosteronism than aldosterone-18-glucuronide ('urinary aldosterone'). However, in several patients with primary aldosteronism even the tetrahydroaldosterone values remained in the normal range. As the possible cause for this observation, the role of intestinal bacteria was considered which may transform tetrahydroaldosterone into 21-deoxytetrahydroaldosterone. Using a 21-deoxytetrahydroaldosterone radioimmunoassay, this hypothesis could be confirmed. The sums of the urinary 21-deoxytetrahydroaldosterone and tetrahydroaldosterone excretions revealed to be of better diagnostic value than the tetrahydroaldosterone values alone.

Adenoma↗
PubMed1979

Effect of posture on the plasma concentrations of aldosterone in hypertension and primary hyperaldosteronism.

Measurement of plasma aldosterone concentrations (PAC) at 8 a.m. and after 4 h in the upright posture can further assist in identifying the adrenal pathologic lesion in patients with primary aldosteronism. Increases in PAC are associated with hyperplasia, and decreases with adenoma. Normal increases in response to upright posture are observed in patients with essential hypertension with normal or reduced renin concentration.

Adolescent↗
PubMed2005

Hyperaldosteronism and hypertension: ethnic differences.

The purpose of this study is to evaluate the relationship between aldosterone and blood pressure in a total of 220 normotensive and 293 essential hypertensive subjects in 2 genetically distinct populations-blacks and white French Canadians. The 24-hour blood pressure monitoring was performed under standardized conditions after discontinuing antihypertensive medications. Plasma renin activity and plasma aldosterone were measured in the supine position and after standing for 10 minutes. Plasma atrial natriuretic factor was also measured. Supine and standing plasma renin activities were lower (P< or =0.01), plasma aldosterone was higher (P<0.0001), and the aldosterone/renin ratios were higher (P<0.0001) in the hypertensive subjects. Atrial natriuretic factor was also higher in the hypertensive subjects (P<0.0001). Among blacks, blood pressures did not correlate with plasma renin activity. However, both average daytime and nighttime systolic and diastolic blood pressures were correlated with supine and standing plasma aldosterone and with the aldosterone/renin ratio (P<0.005 or less). In French Canadians, blood pressures tended to be positively correlated with standing plasma renin activity and aldosterone, but not with the aldosterone/renin ratio. Correlations of blood pressure with aldosterone were more consistent and more striking in blacks than in French Canadians. In both ethnic groups, there were inconsistent correlations of blood pressure with atrial natriuretic factor. These observations are consistent with the hypothesis that aldosterone-induced volume expansion is an important contributor to hypertension, especially in blacks.

Adult↗