Vanessa Venturelli

Reduced levels of N-terminal-proatrial natriuretic peptide in hypertensive patients with metabolic syndrome and their relationship with left ventricular mass.

Objectives The metabolic syndrome (MS) is associated with left ventricular hypertrophy (LVH). Previous evidence has shown that LVH is favoured by low levels of atrial natriuretic peptide (ANP), independently from blood pressure (BP), in hypertension. Although levels of natriuretic peptides are known to be lower in obesity, plasma ANP levels have not yet been assessed in MS. We aimed to assess the ANP levels and their relationship with left ventricular mass (LVM) in patients affected by MS. Methods One hundred and twenty-eight essential hypertensive patients were included in the study: 51 with MS and 77 without MS. Clinical, echocardiographical and biochemical parameters, and levels of both N-terminal (NT)-proANP and alphaANP were assessed. Results Hypertensive patients affected by MS had higher LVM and increased frequency of LVH. NT-proANP levels were significantly lower in MS, independent of waist circumference (WC). Log(NT-proANP) levels were significantly inversely related to left ventricular mass index (LVMI) (β = −0.360, P < 0.001) and LVM/height2.7 (β = −0.370, P < 0.001) in the whole hypertensive population by multiple linear regression analysis. The relationship of log(NT-proANP) with LVM was more enhanced in patients with MS. Conclusions The present study demonstrates that levels of NT-proANP are significantly reduced in hypertensive patients affected by MS, and they are significantly inversely related to the increased LVM observed in these patients. Our findings, while supporting previous experimental and clinical evidence of the antihypertrophic role of ANP in hypertension, may help to identify one of the possible mechanisms directly underlying LVH in MS.

Endothelial dysfunction and stroke.

Summary: Endothelial dysfunction, intended as the complex multifaced pathological product of different vasculotoxic agents or injuries, is viewed today as an attractant intermediate phenotype of cardiovascular diseases with usually long and unpredictable natural history. Furthermore, endothelial dysfunction may not only represent a vascular disease marker, but may actually play an important pathogenetic role, leading to progression of the disease and unfavourable outcomes. Among these vascular diseases, cerebrovascular accidents, namely stroke, clearly represent a paradigmatic example of the potential role of dysfunctional endothelium. In fact, in the worlds growing elderly population few diseases are more dreaded than stroke. With an increasing incidence and mortality of 30%, stroke carries the threat of death or long‐term disability and suffering. Endothelium produces nitric oxide (NO) under basal conditions and in response to a variety of vasoactive stimuli in large cerebral arteries and in the cerebral microcirculation. In addition to exerting a tonic dilator effect on the cerebral circulation, basal release of NO may protect cerebral endothelium by inhibiting aggregation of platelets and leukocytes. In this paper, we analyse current evidence suggesting that endothelial dysfunction can play a role in the pathogenesis of ischaemic stroke.

Effect of a regulatory mutation on the rat atrial natriuretic peptide gene transcription

To investigate the functional relevance of a regulatory mutation affecting the enhancer element PEA2 of the rat ANP gene we transfected rat cardiomyocytes and aortic endothelial cells with either the mutant or the wild-type ANP promoter construct (-683 +54) and performed CAT assays both at baseline and in response to Phenylephrine and Angiotensin II. In the myocardial cells we also determined the DNA/nuclear protein interaction through electrophoretic mobility shift assay. These studies showed a significantly lower degree of ANP transcription in the presence of the mutant PEA2 site, thus demonstrating its functional significance and the biological relevance of ANP gene structural alterations.