Lucia Zanin

Gene expression, localization, and characterization of endothelin A and B receptors in the human adrenal cortex.

Compelling evidence indicates that the endothelium-derived potent vasoconstrictor endothelin-1 (ET-1) stimulates aldosterone secretion by interacting with specific receptors. Although two different ET-1 receptors have been identified and cloned, the receptor subtype involved in mediating aldosterone secretion is still unknown. Accordingly, we wished to investigate whether the genes of ET-1 and of its receptors A and B are expressed in the normal human adrenal cortex. We designed specific primers for ET-1 and the ETA and ETB receptors genes and developed a reverse transcription polymerase chain reaction (RT-PCR) with chemiluminescent quantitation of the cDNA. In addition, we carried out 125I ET-1 displacement studies with cold ET-1, ET-3 and the specific ETA and ETB ligands BQ123 and sarafotoxin 6C. Localization of each receptor subtype was also investigated by autoradiography. Binding experiments were first individually analyzed by Scatchard and Hofstee plot and then coanalyzed by the nonlinear iterative curve fitting program Ligand. Histologically normal adrenal cortex tissue, obtained from kidney cancer patients (n = 7), and an aldosterone-producing adenoma (APA), which is histogenetically derived from the zona glomerulosa (ZG) cells, were studied. Results showed that the ET-1, ETA and ETB mRNA can be detected by RT-PCR in all adrenal cortices as well as in the APA. The best fitting of the 125I ET-1 displacement binding data was consistently provided by a two-site model both in the normal adrenal cortex (F = 22.1, P < 0.0001) and in the APA (F = 18.4, P < 0.0001). In the former the density (Bmax) of the ETA and ETB subtype was 2.6 +/- 0.5 pmol/mg protein (m +/- SEM) and 1.19 +/- 0.6, respectively. The dissociation constant (Kd) of ET-1, ET-3, S6C, and BQ-123 for each receptor subtype resulted to be within the range reported for human tissue for the ETA and ETB receptors. In the APA tissue the Bmax tended to be lower (1.33 and 0.8 pmol/mg protein, for the ETA and ETB, respectively) but the Kd were similar. Autoradiographic studies confirmed the presence of both receptor subtypes on the ZG as well as on APA cells. Thus, the genes of ET-1 and both its receptor subtypes ETA and ETB are actively transcribed in the human adrenal cortex. Furthermore, both receptor subtypes are translated into proteins in ZG and APA cells.

IN PRIMARY ALDOSTERONISM THE CIRCADIAN BLOOD PRESSURE RHYTHM IS SIMILAR TO THAT IN PRIMARY HYPERTENSION

To investigate whether the 24-hour blood pressure (BP) profile of primary aldosteronism differs from that of primary hypertension, ambulatory BP monitoring was performed in 11 patients with primary aldosteronism (9 with an adrenal adenoma and 2 with idiopathic hyperaldosteronism) and in 11 primary hypertensives, matched for sex (5M,6F), age (mean: 52 vs 49 yrs) and casual BP. We found no difference in 24-hour BP, nocturnal BP fall, BP variability (standard deviation and peaks of pressure) response to postural changes (lying-standing BP) between the two groups (all p values n.s.). Within the patients with primary aldosteronism no correlation was observed between BP, plasma renin activity, blood and urine aldosterone levels, blood and urine K+, and size of the tumour. Thus, at variance with previous reports, these results show that diurnal rhythm of BP and BP variability are similar in primary aldosteronism and primary hypertensives with similar demographic features and causal BP levels. They also show that an orthostatic fall of BP is not a common feature in this disease.

A Renin-Secreting Tumour with Severe Hypertension and Cardiova-Scular Disease: A Diagnostic and Therapeutic Challenge

A case of renin-secreting juxtaglomerular cell tumour which presented with a severe hypertensive crisis and did not respond to angiotensin converting enzyme inhibitors but was promptly controlled by intravenous labetalol is reported. The diagnostic difficulties which can be encountered in such cases and the usefulness of the different diagnostic tests, including renal vein renin measurement, are discussed.

Necrosis of a phaeochromocytoma associated with spontaneous remission of diabetes and hypertension

The diagnosis of phaeochromocytoma is sometimes difficult since its clinical presentation is quite variable. We report a 52‐year‐old woman who presented with acute diabetes mellitus and severe hypertension, which spontaneously disappeared. MIBG‐scintigraphy and urine and plasma catecholamines were normal. At surgery, a largely necrotic phaeochromocytoma was found. Pathological examination demonstrated extensive avascular necrosis, which had occurred spontaneously without any major symptoms.