Alessandro Alonzo

Vascular inflammation and endothelial dysfunction in experimental hypertension.

Essential hypertension is characterized by increased peripheral vascular resistance to blood flow. The endothelium is a crucial regulator of vascular tone. Its function is impaired in patients with hypertension, with reduced vasodilation, increased vascular tone associated with a proinflammatory and prothrombotic state. Low-grade inflammation localized in vascular tissue is therefore recognized as an important contributor to the pathophysiology of hypertension, to the initiation and progression of atherosclerosis as well as to the development of cardiovascular diseases.

Natriuretic peptides and cardiovascular damage in the metabolic syndrome: Molecular mechanisms and clinical implications

Natriuretic peptides are endogenous antagonists of vasoconstrictor and salt- and water-retaining systems in the bodys defence against blood pressure elevation and plasma volume expansion, through direct vasodilator, diuretic and natriuretic properties. In addition, natriuretic peptides may play a role in the modulation of the molecular mechanisms involved in metabolic regulation and cardiovascular remodelling. The metabolic syndrome is characterized by visceral obesity, hyperlipidaemia, vascular inflammation and hypertension, which are linked by peripheral insulin resistance. Increased visceral adiposity may contribute to the reduction in the circulating levels of natriuretic peptides. The dysregulation of neurohormonal systems, including the renin-angiotensin and the natriuretic peptide systems, may in turn contribute to the development of insulin resistance in dysmetabolic patients. In obese subjects with the metabolic syndrome, reduced levels of natriuretic peptides may be involved in the development of hypertension, vascular inflammation and cardio vascular remodelling, and this may predispose to the development of cardiovascular disease. The present review summarizes the regulation and function of the natriuretic peptide system in obese patients with the metabolic syndrome and the involvement of altered bioactive levels of natriuretic peptides in the pathophysiology of cardiovascular disease in patients with metabolic abnormalities.

Effects of a Long-Term Treatment With Aliskiren or Ramipril on Structural Alterations of Subcutaneous Small-Resistance Arteries of Diabetic Hypertensive Patients

Structural alterations of subcutaneous small-resistance arteries are associated with a worse clinical prognosis in hypertension and non–insulin-dependent diabetes mellitus. The effects of the direct renin inhibitor aliskiren on microvascular structure were never previously evaluated. Therefore, we investigated the effects of aliskiren in comparison with those of an extensively used angiotensin-converting enzyme inhibitor, ramipril, on peripheral subcutaneous small-resistance artery morphology, retinal arteriolar structure, and capillary density in a population of patients with non–insulin-dependent diabetes mellitus. Sixteen patients with mild essential hypertension and with a previous diagnosis of non–insulin-dependent diabetes mellitus were included in the study. Patients were then randomized to 1 of the 2 active treatments (aliskiren 150 mg once daily, n=9; or ramipril 5 mg once daily, n=7). Each patient underwent a biopsy of the subcutaneous fat from the gluteal region, an evaluation of retinal artery morphology (scanning laser Doppler flowmetry), and capillary density (capillaroscopy), at baseline and after 1 year of treatment. Subcutaneous small arteries were dissected and mounted on a pressurized micromyograph, and the media-to-lumen ratio was evaluated. A similar office blood pressure–lowering effect and a similar reduction of the wall-to-lumen ratio of retinal arterioles were observed with the 2 drugs. Aliskiren significantly reduced media-to-lumen ratio of subcutaneous small-resistance arteries, whereas ramipril-induced reduction of media to lumen ratio was not statistically significant. No relevant effect on capillary density was observed. In conclusion, treatment with aliskiren or ramipril was associated with a correction of microvascular structural alterations in patients with non–insulin-dependent diabetes mellitus.

The direct renin inhibitor aliskiren improves vascular remodelling in transgenic rats harbouring human renin and angiotensinogen genes

In the present study, we tested the hypothesis that chronic treatment with the direct rennin inhibitor aliskiren improves the remodelling of resistance arteries in dTGR (double-transgenic rats). dTGR (5 weeks) were treated with aliskiren (3 mg/kg of body mass per day) or ramipril (1 mg/kg of body mass per day) for 14 days and compared with age-matched vehicle-treated dTGR. BP (blood pressure) was similarly reduced in both aliskiren-treated and ramipril-treated rats compared with control dTGR (167±1 and 169±2 mmHg compared with 197±4 mmHg respectively; P<0.05). The M/L (media-to-lumen) ratio assessed on pressurized preparations was equally reduced in aliskiren-treated and ramipril-treated rats compared with controls (6.3±0.5 and 6.4±0.2% compared with 9.8±0.4% respectively; P<0.05). Endothelium-dependent and -independent relaxations were similar among the groups. L-NAME (N(G)-nitro-L-arginine methyl ester) significantly reduced acetylcholine-induced dilation in drug-treated dTGR. This effect was significantly more prominent in aliskiren-treated rats. eNOS (endothelial NO synthase) expression showed a 2-fold increase only in aliskiren-treated dTGR as compared with controls (P<0.01) and ramipril-treated dTGR (P<0.05). Plasma nitrite, as an index of NO production, was significantly increased in dTGR treated with either aliskiren or ramipril compared with controls. Only aliskiren induced a 2-fold increase in plasma nitrite, which was significantly greater than that induced by ramipril (P<0.05). gp91(phox) expression and ROS (reactive oxygen species) production in aorta were significantly and similarly reduced by both drugs. In conclusion, equieffective hypotensive doses of aliskiren or ramipril reduced the M/L ratio of mesenteric arteries and improved oxidative stress in dTGR. However, only aliskiren increased further NO production in the vasculature. Hence, in dTGR, direct renin inhibition induces favourable effects similar to that induced by ACE (angiotensin-converting enzyme) inhibition in improving vascular remodelling through different mechanisms.

Transfemoral approach with systematic use of FemoSeal™ closure device compared to transradial approach in primary angioplasty

To compare the incidence of major adverse cardiac and cerebrovascular events (MACCE) and thrombolysis in myocardial infarction (TIMI) bleedings in primary percutaneous coronary intervention (pPCI) performed through transradial approach (TRA) or transfemoral approach (TFA) with systematic closure by FemoSeal™.