Ac Pessina

Left ventricular systolic function in primary aldosteronism and hypertension.

Objective This study was designed to investigate whether the excess aldosterone found in primary aldosteronism (PA) influences left-ventricular systolic function (LVSF), through a positive inotropic effect. Methods M-mode and two-dimensional echocardiography and transmitral Doppler flow velocity measurements were performed in 82 patients: 44 with confirmed PA (23 male; 21 female; aged 51.8 ± 13 years) and 38 essential hypertension patients (16 male; 22 female; aged 48.5 ± 12 years) matched for demography and blood pressure (BP) values. We measured left- ventricular (LV) midwall fractional shortening (MwFSho) and LV circumferential end-systolic stress (cESS, calculated according to Reicheks equation) and analysed the relationship between MwFSho and cESS. Results These are given as the mean ± standard deviation. PA patients had significantly higher cardiac index (CI) (3.55 ± 0.94 l/m2 vs 2.98 ± 0.58, P < 0.005) and lower E wave/A wave time-velocity integral ratio (0.93 ± 0.27 vs 1.26 ± 0.41, P < 0.001) than EH, whereas mean BP (126 ± 12 mmHg vs 128 ± 12), MwFSho (17.1 ± 2.4 % vs 16.3 ± 1.9), cESS (118 ± 19 Kdynes/cm2vs 121 ± 18) and the relationship between LV MwFSho and LV cESS did not differ between groups. Conclusion These findings confirm that PA patients exhibit: (1) a modest increase of CI; (2) an LV diastolic filling mainly occurring with the atrial kick. However, they do not lend support to the contention that the excess of plasma aldosterone seen in PA is associated with enhanced LV inotropism under resting conditions.

High angiotensin II state without cardiac remodeling (Bartter’s and Gitelman’s syndromes): Are angiotensin II type 2 receptors involved?

Background/aims: While Angiotensin II (Ang II) is a major factor in the development of cardiomyocyte hypertrophy and a pivotal role for Ang II signals via ERK1/2 has been identified, mechanism(s) responsible are still unclear. As Bartter’s and Gitelman’s syndrome patients (BS/GS) have increased Ang II, and yet normo/hypotension, hyporesponsiveness to pressors and blunted Ang II signaling via type 1 receptors (AT1R), this study assesses BS/GS’s left ventricular (LV) mass and structure as well as Ang II induced ERK1/2 phosphorylation compared with essential hypertensive patients (EH) and normotensive healthy subjects (C) to gain insight into Ang II mediated processes. Methods: Indices of cardiac hypertrophy were determined by M-mode, two-dimensional echo Doppler and ERK phosphorylation by Western blot. Results: None of BS/GS exhibited LV remodelling; LV mass, LV end-diastolic volume and mass/volume ratio were unchanged vs C (60±14 g/m2vs 64±12, 64±12 ml/m2vs 60±8 and 0.95±0.2 vs 1.0±0.2, respectively) and reduced vs EH (119±15, p<0.001, 78±9, p<0.05 and 1.52±0.15, p<0.01). Despite BS/GS’s higher plasma renin activity and aldosterone and unchanged level of AT1R, Ang II induced ERK1/2 phosphorylation was reduced vs both C and EH: 0.64 d.u.±0.08 vs 0.90±0.06 in C, p<0.006, and vs 1.45±0.07 in EH, p<0.001. Conclusion: The data point to a direct cardioremodeling role for Ang II and support a role of Ang II type 2 receptor (AT2R) signaling as involved in the lack of cardiovascular remodeling in BS/GS. However, further studies using more direct approaches to demonstrate the effects of AT2R signaling must be pursued.

Oxidative stress-related proteins in a Conn’s adenoma tissue. Relevance for aldosterone’s prooxidative and proinflammatory activity

Background and aim: Angiotensin II (Ang II) induces oxidative stress (OxSt), which is essential for cardiovascular remodeling. Aldosterone also induces fibrosis and remodeling through direct effect on non-classical mineralocorticoid (MR) target tissues. However, studies on the role of aldosterone on OxSt and related factors in humans are lacking. Materials and methods: We assessed gene and protein expression of p22phox (RT-PCR and Western blot), NAD(P)H oxidase subunit essential for Superoxide production and gene expression of transforming growth fator (TGF) β, plasminogen activator inhibitor (PAI)-1, and heme oxygenase (HO)-1, effectors of OxSt (RT-PCR), in a Conn’s adenoma, removed from a patient with primary hyperaldosteronism. Ang II type 1 (AT1R) and MR receptors expression were also evaluated (RT-PCR). The normal adrenal tissue adjacent to the adenoma was used as control. Results: p22phox gene and protein expression were higher (31% and 53%, respectively) in the adrenal adenoma. TGFβ, PAI-1, and HO-1 gene expression were also higher (25%, 129%, and 25%, respectively) in the adrenal adenoma while AT1 R gene expression was similar (8%). The expression of MR in the adenoma was documented. Conclusions: This report demonstrates in a human model that the increased aldosterone production has effects on enzyme systems related to OxSt, enhancing the systemic fibrogenic effects of aldosterone excess through TGFβ and PAI-1 expression which was previously demonstrated only indirectly in vitro and in animal models. The presence of MR expression in the adenoma may link the hormone with the adenoma growth. Therefore, the results of this study derived from a single case might represent an important working hypothesis for further research in a larger number of cases to clarify the role of aldosterone overproduction on OxSt and its clinical relevance.

Effect of doxazosin on oxidative stress related proteins in essential hypertensive patients.

The role of oxidative stress in the pathophysiology of hypertension has stimulated the investigation of strategies to reduce oxidative stress via antioxidant defenses. Using a molecular biology approach, we report, in essential hypertensive patients, the effect of doxazosin treatment on the mononuclear cell gene and protein expression of two major elements in the oxidative stress and vascular remodeling-related pathways: p22phox and PAI-1. Ten essential hypertensive patients were treated with Doxazosin (4 mg/day) for two weeks (EH + D) and compared with ten untreated hypertensive patients (EH) and ten normotensive subjects (C). In EH p22phox and PAI-1 mRNA and protein level was increased compared with C. In EH + D, doxazosin reduced p22phox and PAI-1 gene and protein expression, which was similar to that of C. These results demonstrate for doxazosin an inhibitory effect on oxidative stress related proteins at gene and protein level, which confirms at molecular level a powerful antioxidant potential for this agent that could translate, in the long term, into a powerful antiatherosclerotic effect.

Bronchocentric granulomatosis and central diabetes insipidus successfully treated with corticosteroids

Bronchocentric granulomatosis (BCG) is a rare chronic granulomatous lung disease that leads to destruction of the airway walls. It has been observed in association with various conditions, but never, so far, been reported to involve the central nervous system. We report a case of histologically confirmed pulmonary bronchocentric granulomatosis temporally associated with a partial central diabetes insipidus (CDI). Although the pathological basis of the posterior pituitary gland involvement was not ascertained, the temporal association of bronchocentric granulomatosis and central diabetes insipidus, as well as the fact that corticosteroid treatment provided stable remission of both conditions after a 10 month follow-up, strongly suggest that central diabetes insipidus was aetiologically related to bronchocentric granulomatosis in this patient.