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Biomedical subjects

Alessandro Lechi

Publications and source records attributed to Alessandro Lechi.

At least 19 recordsLinked to original sources
PubMed2004

Heterosexual relationships among heroin users in Italy.

This study investigated how many stable partners of drug users (DUs) had a history of drug use or were current DUs. Of 589 DUs interviewed, 41% reported that they had a partner with current or previous experience of drug addiction. A strong gender difference emerged: 77% of female DUs reported a stable relationship with partners with a history of addiction, versus only 30% for male DUs. Partners with a history of drug dependence are more likely to be: male, older, with a lower educational level and a lower rate of stable employment than partners without a history of drug addiction. Logistic regression analysis indicated that the characteristics of heroin users who have current partners with histories of drug use include: female gender, older age, living with a partner, lengthy duration of the relationship and HIV positive status. Fewer subjects are married if the partner has a history of addiction, and there is an association between lengthy drug use and partner without drug addiction history. The high percentage (59%) of subjects who were in stable relationships with partners without histories of heroin addiction and the relatively long duration of these relationships, raises the issue of possible transmission of blood-borne viruses from the DUs to their sexual partners. The study does suggest the need for consideration of sexual partnerships and gender differences in providing drug abuse treatment for heroin users.

Adult↗
PubMed2004

Co-administration of nitric oxide-aspirin (NCX-4016) and aspirin prevents platelet and monocyte activation and protects against gastric damage induced by aspirin in humans.

OBJECTIVES: The goal of this study was to test the hypothesis that NCX-4016 may have broader anti-inflammatory and antithrombotic effects as well as better gastric tolerability than aspirin in humans. BACKGROUND: NCX-4016 is an aspirin derivative containing a nitric oxide-releasing moiety that prevents platelet activation and modulates tissue factor (TF) expression and cytokine release from lipopolysaccharide (LPS)-stimulated monocytes. METHODS: This was a blind-observer, placebo-controlled, parallel-group study in which 48 healthy subjects were randomized to receive NCX-4016 800 mg twice a day, NCX-4016 800 mg twice a day plus aspirin 325 mg, aspirin 325 mg, or placebo for 21 days. RESULTS: Similar to aspirin alone, NCX-4016 effectively inhibited platelet aggregation induced by 0.6 mmol/ arachidonic acid, clot-stimulated thromboxane (TX) B2 generation in whole blood, and urinary excretion of 11-dehydro-TXB2. Unlike aspirin alone, the administration of NCX-4016 significantly inhibited TF expression in monocytes stimulated ex vivo with 10 micromol/l LPS (determined by flow-cytometry analysis of TF on CD14 positive cells). NCX-4016 also inhibited the rapid TF expression induced in monocytes by a proteinase activated receptor agonist (thrombin receptor activator protein, 2 micromol/l) as well as LPS-induced expression of CD11b . Ex vivo, release of MCP-1 and interleukin-6 were significantly inhibited by NCX-4016, but not by aspirin. NCX-4016 was not associated with gastric damage, and significantly reduced gastric injury when co-administered with aspirin, although both drugs reduced gastric PGE2 production to the same extent. CONCLUSIONS: NCX-4016 is equally effective as aspirin in inhibiting cyclooxygenase activity. However, NCX-4016 causes less gastric damage and prevents monocyte activation. Larger multicenter trials are warranted to establish clinical efficacy and safety of NCX-4016.

Administration, Oral↗
PubMed2004

Immunogenicity, reactogenicity and adherence with hepatitis A vaccination among drug users.

Hepatitis A virus (HAV) vaccination is recommended in drug users (DUs) because this population has a very high prevalence of hepatitis C virus, and additional infection with HAV can lead to increased morbidity and mortality. The efficacy of hepatitis A vaccine (1440 ELISA units), in terms of immunogenicity, reactogenicity and compliance among 44 heroin DUs using a 0-6 month schedule was investigated. Three subjects (6.8%) experienced adverse reactions. After the first dose of hepatitis A vaccine, 37% of subjects seroconverted. Two months after the 6-month booster vaccination, all vaccinated patients became seropositive. The mean serum antibody concentration was 40 mIU/ml after 6 months and 558 mIU/ml after 8 months. Although all DUs proved seropositive after the booster vaccination, the seroconversion rate, at the 2 and 6 months time points was much lower than in healthy subjects. The lower geometric mean titre could affect the kinetics of decrease of antibody titres and the protection conferred by vaccination may be less durable in these patients. These findings indicate that the 0-12 months schedule could be reduced to a shorter 0-6 months schedule in order to shorten the unprotected period. Further studies among drug users are needed to explore the efficacy and immunogenicity of higher doses or alternative schedules of HAV vaccine.

Adult↗
PubMed2004

Acute hyperhomocysteinemia induces a reduction in arterial distensibility and compliance.

OBJECTIVE: The aim of the study was to evaluate the effects of acute hyperhomocysteinemia on distensibility and compliance of large peripheral arteries. Isoprostanes generation and antioxidant vitamins were used to assess the role of oxidative stress. DESIGN: A cross-over, double-blind study on distensibility (DC: distensibility coefficient) and compliance (CC: cross-sectional compliance) of common femoral and brachial arteries was performed in 12 healthy young male volunteers by means of a wall track system before and 4 h after a single oral methionine (100 mg/kg) or placebo administration. The effects of methionine load were investigated also after oral administration of vitamin C (1g/day) and vitamin E (800 mg/day) for 8 consecutive days. RESULTS: Oral methionine induced a significant increase in plasmatic levels of homocysteine. Distensibility and compliance of brachial and femoral arteries were significantly reduced after methionine load in comparison to placebo. This acute impairment of arterial wall mechanical properties was associated to endothelial dysfunction, since altered flow-dependent vasodilatation (P < 0.05 versus placebo) was observed in the same arterial districts. A significant increase in urinary 8-iso-prostaglandin F2alpha was observed after methionine. Pretreatment with vitamins C and E prevented the effects of methionine on femoral and brachial arteries as well as on urinary 8-iso-prostaglandin F2alpha excretion. CONCLUSIONS: Hyperhomocysteinemia seems responsible for altered arterial wall elasticity and for endothelial dysfunction. A pivotal role can be attributed to oxidative stress.

Acute Disease↗
PubMed2003

Determinants of platelet activation in human essential hypertension.

Experimental data suggest that oxidative stress might be enhanced in hypertension and contribute to platelet activation. We hypothesized that both oxidative stress and platelet activation could be related to the clinical characteristics of hypertensive patients. The urinary excretion of 11-dehydrothromboxane (TX) B2, reflecting in vivo platelet activation, was measured in 75 patients with mild to severe essential hypertension and 75 pair-matched, healthy controls. The urinary excretion of 8-iso-prostaglandin (PG) F2alpha was determined as an index of in vivo lipid peroxidation. Urinary 11-dehydro-TXB2 was significantly higher in essential hypertensives compared with controls. Although no statistically significant difference in urinary 8-iso-PGF2alpha was observed between patients and controls, plasma vitamin C was lower and plasma homocysteine higher in hypertensive patients than in controls. Both urinary 11-dehydro-TXB2 and 8-iso-PGF2alpha were higher in patients with advanced hypertensive retinopathy compared with patients without retinopathy. Multivariate linear regression analysis identified urinary 8-iso-PGF2alpha, plasma fibrinogen, homocysteine, and vitamin E as the only variables independently correlated with urinary 11-dehydro-TXB2. Logistic regression analysis showed that high urinary 8-iso-PGF2alpha, plasma fibrinogen, and homocysteine, as well as low plasma vitamin E, advanced retinopathy, elevated diastolic blood pressure, and the absence of antihypertensive treatment, were predictors of high urinary 11-dehydro-TXB2. We demonstrated increased oxidative stress and persistent platelet activation in essential hypertensives with advanced vascular lesions. These findings might help identify hypertensive patients who are at increased risk of cardiovascular events and who might benefit from long-term antiplatelet therapy.

Adolescent↗
PubMed2003

Factors associated with hepatitis C virus infection in injection and noninjection drug users in Italy.

We describe the prevalence of hepatitis C virus (HCV) infection among noninjection users of heroin in Italy and compare the prevalence of HCV infection among noninjection drug users (NIDUs) and injection drug users (IDUs). Multiple logistic regression analysis of data from NIDUs showed that hepatitis B virus (HBV) infection status was the only independent predictor of HCV seroprevalence. Among IDUs, the number of years of drug use and HBV and human immunodeficiency virus infection status were independent predictors of HCV seropositivity. We found an HCV infection prevalence of 20% among NIDUs. This rate was much lower than that for IDUs, who are 11 times more likely to have antibodies against HCV. The prevalence of HCV infection was much higher than that of HBV infection among the IDUs. In contrast, the prevalence of HBV infection was slightly higher than that of HCV infection among unvaccinated NIDUs. The prevalence of HCV infection among long-term IDUs approached true population saturation; among long-term NIDUs, however, it appeared to plateau at approximately 40%. Additional research on HCV infection among NIDUs is needed to develop a strategic prevention program for this patient subgroup.

Adult↗
PubMed2003

Autonomic system activity and 24-hour blood pressure variations in subjects with normal- and high-tension glaucoma.

PURPOSE: As suggested by findings of abnormal responses to posture in patients with normal-tension glaucoma (NTG), cardiovascular autoregulation may also be defective in primary open-angle glaucoma (POAG). PATIENTS AND METHODS: Both 24-hour ambulatory blood pressure monitoring and the head-up tilt test were performed in 17 subjects with NTG and in 13 subjects with high-tension POAG (ht-POAG). These groups were compared with 17 age-matched healthy individuals. Subjects undergoing cardiovascular therapy were excluded. RESULTS: No significant differences in diurnal and nocturnal blood pressure and heart rate were found between the groups. A significant reduction in diurnal heart rate variability was found in NTG (12.1 +/- 2.8 bpm) compared with the ht-POAG (15.0 +/- 2.4 bpm, P < 0.01) and control groups (15.8 +/- 3.0 bpm, P = 0.01]). Nocturnal diastolic blood pressure variability was also reduced in NTG (6.9 +/- 2.2 mm Hg) compared with controls (8.6 +/- 2.3 mm Hg, P < 0.05]) as was heart rate variability (6.3 +/- 1.4 vs 8.3 +/- 2.6 in ht-POAG, P < 0.05), suggesting blunted blood pressure and heart rate modulation in NTG subjects. Spectral analysis of short-term heart rate variability showed a significant reduction of total power in the supine position (1064 +/- 600 in NTG vs 1688 +/- 889 ms2 in controls, P < 0.05]). This was not accompanied either by a physiological reduction in total power or in a high-frequency component during the passive orthostatic stimulus. These differences tend to become more prominent in the clinically more severe forms of NTG (as identified by scores based on the extent of optic disk excavation, visual field damage, and progression of disease). This would suggest a correlation between the extent of autonomic disorder and severity of glaucoma. The alpha index (root-square of low-frequency heart rate to low-frequency blood pressure ratio) was lower in the supine position in NTG subjects (8.1 +/- 3.1 vs 10.6 +/- 3.3 ms/mm Hg in controls, P < 0.05), confirming the reduced baroreflex sensitivity. CONCLUSIONS: The results confirm the hypothesis that dysfunction of autonomic control of the cardiovascular response may be a contributing pathogenetic factor in NTG, inducing a chronic ischemia of the optic nerve.

Autonomic Nervous System↗
PubMed2003

Intralymphocyte magnesium decrease in patients with primary aldosteronism. Possible links with cardiac remodelling.

Our group have described a group of patients with primary aldosteronism which is characterized by significantly decreased intralymphocyte ionized magnesium concentration. Some models of experimental hyperaldosteronism are characterized by cardiovascular fibrosis but despite this fact the link between a negative magnesium balance and fibrosis is lacking. Consequently, to shed some light on the relationships between magnesium and tissue fibrosis we tested the in vitro effects of incubating human fibroblasts in low magnesium medium on mRNA collagen I and III gene expression by northern blot analysis. Both collagen I and III mRNA gene expression were increased by magnesium deprivation. The increase in collagen expression was similar for both collagen I and III. These data are in favour of a potential link between magnesium homeostasis and collagen synthesis. A physiopathologic mechanism linking magnesium homeostasis to the state of collagen turnover may have important clinical correlates such as cardiac remodelling in congestive heart failure.

Cell Line↗
PubMed2002

NCX-4016 (NO-aspirin) inhibits lipopolysaccharide-induced tissue factor expression in vivo: role of nitric oxide.

BACKGROUND: NCX-4016 is an acetylsalicylic acid (ASA) derivative containing a nitric oxide-releasing moiety. Compared with ASA, NCX-4016 has a broader spectrum of antithrombotic and antiinflammatory activities. We hypothesized that NCX-4016 might inhibit in vivo lipopolysaccharide (LPS)-induced expression of tissue factor (TF). METHODS AND RESULTS: Rats were administered 90 mg/kg NCX-4016 orally for 5 days. Placebo, 50 mg/kg ASA, and 80 mg/kg isosorbide-5-mononitrate (ISMN) were used in control groups. On day 5, rats were injected intraperitoneally with 100 microg/kg LPS and killed 6 hours later. The expression of TF in monocytes was measured by flow cytometry and Western blot analysis. Reverse transcriptase-polymerase chain reaction was performed to assess expression of TF and cyclooxygenase-2 (COX-2) genes. Plasma concentrations of interleukin-1beta and tumor necrosis factor-alpha were measured. Urine samples were collected to evaluate the excretion of the thromboxane metabolite 11-dehydro-thromboxane (TX)B2. Gastric mucosa was inspected. LPS injection was followed by synthesis TF and COX-2 mRNAs in circulating monocytes, which were blunted by NCX-4016 but not by ASA or ISMN. Both NCX-4016 and ISMN reduced TF expression on surface of circulating monocyte. LPS increased the excretion 11-dehydro-TXB2, and this was prevented by NCX-4016 and ASA. Unlike ASA, NCX-4016 reduced plasma interleukin-1beta and tumor necrosis factor-alpha. In addition, NCX-4016 almost completely prevented mucosal damage, whereas ASA increased the extension of gastric lesions in LPS-injected rats. CONCLUSIONS: NCX-4016 prevents monocyte TF expression; this is accompanied by inhibition of TX and cytokine biosynthesis. These additive effects of nitric oxide release and COX inhibition may help explain efficacy and tolerability of NCX-4016.

Administration, Oral↗
PubMed2002

Increased oxidative stress and platelet activation in patients with hypertension and renovascular disease.

BACKGROUND: Hypertensive patients with renovascular disease (RVD) may be exposed to increased oxidative stress, possibly related to activation of the renin-angiotensin system. METHODS AND RESULTS: We measured the urinary excretion of 8-iso-prostaglandin (PG) F2alpha and 11-dehydro-thromboxane (TX) B2 as indexes of in vivo lipid peroxidation and platelet activation, respectively, in 25 patients with RVD, 25 patients with essential hypertension, and 25 healthy subjects. Plasma renin activity in peripheral and renal veins, angiotensin II in renal veins, cholesterol, glucose, triglycerides, homocysteine, and antioxidant vitamins A, C, and E were also determined. Patients were also studied 6 months after a technically successful angioplasty of the stenotic renal arteries. Urinary 8-iso-PGF2alpha was significantly higher in patients with RVD (median, 305 pg/mg creatinine; range, 124 to 1224 pg/mg creatinine) than in patients with essential hypertension (median, 176 pg/mg creatinine; range, 48 to 384 pg/mg creatinine) or in healthy subjects (median, 123 pg/mg creatinine; range, 58 to 385 pg/mg creatinine). Urinary 11-dehydro-TXB2 was also significantly higher in RVD patients compared with healthy subjects. In RVD patients, urinary 8-iso-PGF2alpha correlated with 11-dehydro-TXB2 (r(s)=0.48; P<0.05) and renal vein renin (r(s)=0.67; P<0.005) and angiotensin II (r(s)=0.65; P=0.005) ratios. A reduction in 8-iso-PGF2alpha after angioplasty was observed in RVD patients with high baseline levels of lipid peroxidation. Changes in 8-iso-PGF2alpha were related to baseline lipid peroxidation (r(s)=-0.73; P<0.001), renal vein angiotensin II (r(s)=-0.70; P<0.01) and renin (r(s)=-0.63; P<0.05) ratios. CONCLUSIONS: Lipid peroxidation is markedly enhanced in hypertensive patients with RVD and is related to activation of the renin-angiotensin system. Moreover, persistent platelet activation triggered or amplified by bioactive isoprostanes may contribute to the progression of cardiovascular and renal damage in this setting.

Adolescent↗
PubMed2002

Beta2 integrin-dependent neutrophil adhesion induced by minimally modified low-density lipoproteins is mainly mediated by F2-isoprostanes.

BACKGROUND: Oxidation of LDL produces a series of biologically active, oxidized lipids. Among them, isoprostanes, and in particular iPF(2alpha)-III, seem to be crucial in mediating some of the key cellular events seen in myocardial ischemia-reperfusion injury. METHODS AND RESULTS: Minimally modified LDL (MM-LDL) triggers a dose-dependent, very rapid neutrophil adhesion to human fibrinogen. Rapid adhesion triggering correlates with degree of LDL oxidation and accumulation of isoprostanes. Isoprostanes accumulated in MM-LDL are major determinants of the proadhesive effect of oxidized LDL, as shown by experiments of receptor functional deletion. Moreover, evidence is provided of expression on human neutrophils of a biological active isoprostane receptor distinct from the classical thromboxane A2 receptor. CONCLUSIONS: These data suggest that isoprostanes are major contributors to the proadhesive effect induced by MM-LDL on neutrophils and provide additional evidence for the involvement of isoprostanes in the pathogenesis of myocardial ischemia/reperfusion injury.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2002

Glucose-induced alterations of intracellular ionized magnesium in human lymphocytes.

The intracellular ionic content of human erythrocytes may be altered by hyperglycaemia. Despite this, very little is known about the cellular mechanisms linking glucose and cellular magnesium homeostasis. We measured intracellular ionized magnesium in human lymphocytes, by means of a fluorimetric technique, total intracellular magnesium by means of atomic absorption spectrophotometry and intracellular ATP by means of HPLC. The incubation of lymphocytes with D-glucose in the absence of insulin was followed by a significant decrease in intracellular ionized magnesium; this effect did not occur when the cells were incubated with L-glucose. The effect of glucose on intracellular ionized magnesium was blocked by amphotericin B and the EC(50) of the effect of glucose on intracellular ionized magnesium was about 5 mmol/l of glucose. The increase of intracellular ionized magnesium in cells incubated in the absence of glucose was followed by a decrease in intracellular ATP. In a Na(+)-free medium the decrease of intracellular ionized magnesium in the presence of glucose was still present and the incubation of lymphocytes with glucose did not modify total intralymphocyte magnesium. By selective permeabilization of cell membranes, we established that glucose could not increase compartmentalized intracellular ionized magnesium. Our data supports the hypothesis that glucose per se induces a substantial decrease in intracellular ionized magnesium, which is probably due to an augmented binding of intracellular ionized magnesium to cellular ATP.

Acid Phosphatase↗
PubMed2002

Insulin causes endothelial dysfunction in humans: sites and mechanisms.

BACKGROUND: Insulin resistance is often accompanied by hyperinsulinemia and may predispose to atherosclerosis. Endothelium plays a central role in atherogenesis. The in vivo effects of hyperinsulinemia on endothelial function of large conduit arteries are unknown. METHODS AND RESULTS: Twenty-five healthy subjects were enrolled for study. In study A (n=9), subjects underwent both a time-control saline study and a euglycemic low-dose insulin (insulin approximately 110 pmol/L) clamp for 6 hours. Study B (n=5) was identical to study A except that the euglycemic clamp was performed at high physiological insulin concentrations (approximately 440 pmol/L). In study C (n=7), subjects underwent two 4-hour euglycemic insulin (approximately 110 pmol/L) clamps with and without the concomitant infusion of an antioxidant (vitamin C). In study D (n=4), two saline time-control studies were performed with and without the concomitant infusion of vitamin C. In all studies, both at baseline and throughout the experimental period, endothelium-dependent (flow-mediated) and endothelium-independent (nitroglycerin-induced) vasodilation was assessed in femoral and brachial arteries by echo Doppler. Both low (study A) and high physiological (study B) hyperinsulinemia abolished endothelium-dependent vasodilation, whereas endothelium-independent vasodilation was unaffected. Vitamin C fully restored insulin-impaired endothelial function without affecting endothelium-independent vasodilation (study C). Vitamin C had no effects on endothelium-dependent or endothelium-independent vasodilation during saline control studies (study D). CONCLUSIONS: Modest hyperinsulinemia, mimicking fasting hyperinsulinemia of insulin-resistant states, abrogates endothelium-dependent vasodilation in large conduit arteries, probably by increasing oxidant stress. These data may provide a novel pathophysiological basis to the epidemiological link between hyperinsulinemia/insulin-resistance and atherosclerosis in humans.

Adult↗
PubMed2002

Compliance with hepatitis B vaccination in 1175 heroin users and risk factors associated with lack of vaccine response.

AIMS: To investigate the feasibility of hepatitis B vaccination among heroin users, assessing adherence to the vaccination schedules and identifying factors associated with antibody response. DESIGN AND PARTICIPANTS: A large cohort study in nine public centres for drug users (PCDUs) in north-eastern Italy, with data collected between January 1989 and December 1998. A total of 1175 heroin users were selected and vaccinated with a recombinant vaccine using two schedules (0-1-6 months and 0-1-2 months). FINDINGS: Eighty-eight per cent of patients completed the vaccination series and a protective antibody response occurred in 77% of subjects. Completion of the vaccination series was not related to the length of the vaccination schedule or whether the patient was still in drug abuse treatment at the end of the series, but was related strongly to the number of patients enrolled at each PCDU (Spearman correlation = - 0.93, P < 0.001). Four variables were significantly associated with lack of seroconversion in response to vaccination: older age (AOR = 0.91 per year, 95% CI 0.88-0.94, P < 0.001), 2-month vaccination schedule (AOR = 3.10, 95% CI 2.06-4.68, P < 0.001), HCV seropositivity (AOR = 0.69, 95% CI 0.47-0.99, P = 0.04), HIV seropositivity (AOR = 0.27, 95% CI 0.10-0.77, P = 0.01). CONCLUSIONS: A large-scale, multi-site hepatitis B vaccination programme for heroin users proved feasible and effective. The factors associated with a lack of antibody response may be useful in identifying patients who would benefit most from routine post-vaccination testing, with booster doses for non-responders. These results suggest that hepatitis B vaccination for drug users should become a routine public health practice.

Adult↗
PubMed2002

Prevalence of tuberculosis infection and comparison of multiple-puncture liquid tuberculin test and Mantoux test among drug users.

In order to determine the prevalence of latent infection due to Mycobacterium tuberculosis in drug users and to provide centres for drug users with a practical tool for tuberculosis screening, 237 drug users were subjected to the Monotest and, for reference purposes, to the Mantoux test. The overall prevalence of subjects with a tuberculin skin reaction size > or = 5 mm in the Mantoux test was 25.7%; utilizing a cut-off of > or = 10 mm, the prevalence was 11.4%. Irrespective of cut-off, the Monotest showed a sensitivity of > 90% and a specificity of > 80%. At a prevalence of 25.7%, and with cut-offs of > or = 5 or > or = 10 mm, the positive predictive value was 83% or 62.2%, respectively. Irrespective of cut-off, the negative predictive value was > 97%. In conclusion, the Monotest proved satisfactory as a tool for epidemiological screening in a population with a high prevalence for latent tuberculosis, namely drug users.

Adult↗
PubMed2002

Collagen I and III mRNA gene expression and cell growth potential of skin fibroblasts in patients with essential hypertension.

OBJECTIVES: Despite the claimed disregulation of extracellular matrix synthesis and the increased proliferation rate of different cell types in experimental models of hypertension, very few data are available on collagen synthesis and the proliferation rate of fibroblasts in essential hypertensive patients. DESIGN: We measured collagen I, collagen III, histone H3 mRNA gene expression, collagen protein concentration and thymidine incorporation in fibroblasts from 17 essential hypertensive patients (EH) and 13 healthy normotensive control subjects (NC). METHODS: A Northern blot analysis was performed on fibroblasts in culture obtained from skin biopsies. Collagen protein concentration and DNA synthesis were measured by means of incorporation of tritiated proline and tritiated thymidine, respectively. RESULTS: In cultivated fibroblasts from hypertensives, the expression of collagen III mRNA after addition of fetal calf serum was significantly increased in comparison with that of normotensive-derived cells. After addition of fetal calf serum, collagen protein was statistically increased in cultures from EH patients as compared to NC. In hypertensives, the expression of histone H3 mRNA as well as tritiated thymidine incorporation were both increased as compared to normotensives. CONCLUSIONS: Our data suggest that cultivated fibroblasts from essential hypertensive patients are characterized by an increased expression of type III collagen mRNA and collagen protein synthesis in response to fetal serum, as compared to normotensive-derived cells. Cells from hypertensives are characterized by an increased rate of proliferation after addition of fetal serum, as ascertained by increased thymidine incorporation and increased histone H3 mRNA gene expression, as compared to normotensive-derived cells. This phenotype could be genetically determined and may have an important role in the pathogenesis of essential hypertension.

Adult↗
PubMed2002

Effects of nebivolol and atenolol on small arteries and microcirculatory endothelium-dependent dilation in hypertensive patients undergoing isometric stress.

OBJECTIVE: To examine the effects on small arteries and on the cutaneous microcirculatory system of nebivolol and atenolol in hypertensive patients. DESIGN: Twenty hypertensive patients were randomly assigned to receive nebivolol or atenolol in a single-blind, placebo-controlled cross-over study. Piezoelectric plethysmography on the third finger, laser Doppler on the third finger at rest and after iontophoretic administration of acetylcholine, and pressure-heart rate monitoring, were carried out both at rest and during handgrip. The tests were performed 45 min after 5 mg nebivolol or 100 mg atenolol administration, then repeated 2 days later with a placebo and, after a further 2 days, with atenolol or nebivolol again. RESULTS: Both atenolol and nebivolol reduced diastolic blood pressure values and heart rate, as well the increase of blood pressure and heart rate during handgrip. No change was recorded after placebo. Piezoelectric plethysmography showed a significant increase in the ratio between time to peak and total time (PT/TT), calculated on the sphygmic wave, during handgrip (0.295 0.005 versus 0.231 0.015, P<0.005). After nebivolol, a decrease was recorded in rest conditions (0.185 0.008 versus 0.231 0.015, P<0.005) with no statistically significant increase during handgrip, whereas atenolol showed an increase in the PT/TT ratio at rest, with a sustained response during handgrip. Laser Doppler showed an increased response to acetylcholine only after nebivolol. CONCLUSIONS: Nebivolol and atenolol significantly reduced diastolic blood pressure and heart rate, favourably modulating response to handgrip. Nebivolol improved small artery distensibility index. Endothelium-dependent cutaneous vasodilation after acetylcholine demonstrated a lack of response with atenolol whereas nebivolol favourably acts on endothelial function.

Acetylcholine↗