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Author

Lorenzo Ghiadoni

Other affiliations: Great Ormond Street Hospital
Bio: Lorenzo Ghiadoni is an academic researcher from University of Pisa. The author has contributed to research in topics: Endothelial dysfunction & Essential hypertension. The author has an hindex of 64, co-authored 305 publications receiving 15404 citations. Previous affiliations of Lorenzo Ghiadoni include Great Ormond Street Hospital.


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TL;DR: In essential hypertensive patients, impaired endothelial vasodilation can be improved by the antioxidant vitamin C, an effect that can be reversed by the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine, and these findings support the hypothesis thatNitric oxide inactivation by oxygen free radicals contributes to endothelial dysfunction in essential hypertension.
Abstract: Background—Essential hypertension is associated with impaired endothelium-dependent vasodilation. Inactivation of endothelium-derived nitric oxide by oxygen free radicals participates in endothelial dysfunction in experimental hypertension. To test this hypothesis in humans, we evaluated the effect of antioxidant vitamin C on endothelium-dependent responses in essential hypertensive patients. Methods and Results—In 14 healthy subjects (47.1±4.8 years; blood pressure, 120.6±4.5/80.9±3.5 mm Hg) and 14 essential hypertensive patients (47.3±5.1 years; blood pressure, 153.9±7.1/102.3±4.1 mm Hg), we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 μg · 100 mL−1 · min−1) or sodium nitroprusside (1, 2, and 4 μg/100 mL forearm tissue per minute), an endothelium-dependent and -independent vasodilator, respectively, in basal conditions and during infusion of intrabrachial vitamin C (2.4 mg/100 mL forearm tissue per minute). I...

739 citations

Journal ArticleDOI
TL;DR: There is a blunted response to acetylcholine with advancing age in both normotensive control subjects and essential hypertensive patients, suggesting that aging is associated with reduced endothelium-dependent vasodilation in humans.
Abstract: Background Experimental data from normotensive and hypertensive animals indicate that aging is associated with impaired endothelium-dependent relaxations to acetylcholine, and this possibility appears to be confirmed in the human coronary artery. In the present study, we evaluated the effect of age on endothelial responsiveness in the forearm vessels of either normotensive control subjects or essential hypertensive patients. Methods and Results Within the normotensive or hypertensive group (n=53 and n=57, respectively), subjects were selected with similar blood pressure, plasma cholesterol, and glucose values, and hypercholesterolemic subjects, diabetics, and smokers were excluded. We evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 μg/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 μg/100 mL per minute), an endothelium-independent vasodilator. Acetylcholine caused a dose-dependent vasodilation that was significantly ( P <.01) lower in essential hypertensive patients than in normotensive control subjects. However, a significant negative correlation was observed between acetylcholine-induced vasodilation and patient age in both normotensive ( r =−.86, P <.001) and hypertensive ( r =−.85, P <.001) patients. In contrast, vasodilation to sodium nitroprusside was similar in normotensive control subjects and essential hypertensive patients with a poorer inverse correlation with patient age (normotensive control subjects, r =−.37; hypertensive patients, r =−.36) compared with acetylcholine. Conclusions The present data indicate that there is a blunted response to acetylcholine with advancing age in both normotensive control subjects and essential hypertensive patients, suggesting that aging is associated with reduced endothelium-dependent vasodilation in humans.

718 citations

Journal ArticleDOI
TL;DR: In normotensive individuals, an earlier primary dysfunction of the NO system and a later production of oxidative stress cause age-related reduction in endothelium-dependent vasodilation, which is similar but anticipated in hypertensive patients compared withnormotensive subjects.
Abstract: Age-related endothelial dysfunction could be caused by an alteration in the L-arginine-NO system and the production of oxidative stress in both normotensive and hypertensive individuals. In 47 normotensive subjects and 49 patients with essential hypertension, we evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial sodium nitroprusside (1, 2, and 4 microg/100 mL per minute) and acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-independent vasodilator and an endothelium-dependent vasodilator, respectively. Acetylcholine was repeated in the presence of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL per minute), the antioxidant vitamin C (8 mg/100 mL per minute), or both. Vasodilation to acetylcholine, but not to sodium nitroprusside, was lower (P 60 years). In young hypertensive patients (age 30 years, vitamin C enhanced endothelium-dependent vasodilation and restored the inhibiting effect of L-NMMA on response to acetylcholine. In normotensive individuals, an earlier primary dysfunction of the NO system and a later production of oxidative stress cause age-related reduction in endothelium-dependent vasodilation. These alterations are similar but anticipated in hypertensive patients compared with normotensive subjects.

648 citations

Journal ArticleDOI
TL;DR: These findings suggest that brief episodes of mental stress, similar to those encountered in everyday life, may cause transient endothelial dysfunction in healthy young individuals and might represent a mechanistic link between mental stress and atherogenesis.
Abstract: BACKGROUND: Mental stress has been linked to increased morbidity and mortality in coronary artery disease and to atherosclerosis progression. Experimental studies have suggested that damage to the endothelium may be an important mechanism. METHODS AND RESULTS: Endothelial function was studied in 10 healthy men (aged 50. 4+/-9.6 years) and in 8 non-insulin-dependent diabetic men (aged 52. 0+/-7.2 years). Brachial artery flow-mediated dilation (FMD, endothelium dependent) and response to 50 microg of sublingual glyceryl trinitrate (GTN, endothelium independent) were measured noninvasively by use of high-resolution ultrasound before and after (30, 90, and 240 minutes) a standardized mental stress test. The same protocol without mental stress was repeated on a separate occasion in the healthy men. In healthy subjects, FMD (5.0+/-2.1%) was significantly (P:<0.01) reduced at 30 and 90 minutes after mental stress (2.8+/-2.3% and 2.3+/-2.4%, respectively) and returned toward normal after 4 hours (4.1+/-2.0%). Mental stress had no effect on the response to GTN. In the repeated studies without mental stress, FMD did not change. The diabetic subjects had lower FMD than did the control subjects (3.0+/-1.5% versus 5.0+/-2.1%, respectively; P:=0.02) but showed no changes in FMD (2.7+/-1.1% after 30 minutes, 2.8+/-1.9% after 90 minutes, and 3.1+/-2.3% after 240 minutes) or GTN responses after mental stress. CONCLUSIONS: These findings suggest that brief episodes of mental stress, similar to those encountered in everyday life, may cause transient (up to 4 hours) endothelial dysfunction in healthy young individuals. This might represent a mechanistic link between mental stress and atherogenesis.

625 citations

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TL;DR: It is suggested that regular physical activity can at least in part prevent the age-induced endothelial dysfunction, probably the restoration of nitric oxide availability consequent to prevention of production of oxidative stress.
Abstract: Background—Aging is associated with increased cardiovascular risk and endothelial dysfunction. Since exercise can improve endothelium-dependent vasodilation, in the present study we tested whether long-term physical activity could prevent aging-related endothelial dysfunction. Methods and Results—In 12 young and elderly (age 26.9±2.3 and 62.9±5.8 years, respectively) healthy sedentary subjects and 11 young and 14 elderly matched athletes (age 27.5±1.9 and 66.4±6.1 years, respectively), we studied (with strain-gauge plethysmography) forearm blood flow modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 μg/100 mL per minute), an endothelium-dependent vasodilator, at baseline, during infusion of NG-monomethyl-l-arginine (L-NMMA) (100 μg/100 mL forearm tissue per minute), a nitric oxide–synthase inhibitor, vitamin C (8 mg/100 mL forearm tissue per minute), an antioxidant, and finally under simultaneous infusion of L-NMMA and vitamin C. The response to sodium nitroprusside (1, 2,...

477 citations


Cited by
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Giuseppe Mancia1, Robert Fagard, Krzysztof Narkiewicz, Josep Redon, Alberto Zanchetti, Michael Böhm, Thierry Christiaens, Renata Cifkova, Guy De Backer, Anna F. Dominiczak, Maurizio Galderisi, Diederick E. Grobbee, Tiny Jaarsma, Paulus Kirchhof, Sverre E. Kjeldsen, Stéphane Laurent, Athanasios J. Manolis, Peter M. Nilsson, Luis M. Ruilope, Roland E. Schmieder, Per Anton Sirnes, Peter Sleight, Margus Viigimaa, Bernard Waeber, Faiez Zannad, Michel Burnier, Ettore Ambrosioni, Mark Caufield, Antonio Coca, Michael H. Olsen, Costas Tsioufis, Philippe van de Borne, José Luis Zamorano, Stephan Achenbach, Helmut Baumgartner, Jeroen J. Bax, Héctor Bueno, Veronica Dean, Christi Deaton, Çetin Erol, Roberto Ferrari, David Hasdai, Arno W. Hoes, Juhani Knuuti, Philippe Kolh2, Patrizio Lancellotti, Aleš Linhart, Petros Nihoyannopoulos, Massimo F Piepoli, Piotr Ponikowski, Juan Tamargo, Michal Tendera, Adam Torbicki, William Wijns, Stephan Windecker, Denis Clement, Thierry C. Gillebert, Enrico Agabiti Rosei, Stefan D. Anker, Johann Bauersachs, Jana Brguljan Hitij, Mark J. Caulfield, Marc De Buyzere, Sabina De Geest, Geneviève Derumeaux, Serap Erdine, Csaba Farsang, Christian Funck-Brentano, Vjekoslav Gerc, Giuseppe Germanò, Stephan Gielen, Herman Haller, Jens Jordan, Thomas Kahan, Michel Komajda, Dragan Lovic, Heiko Mahrholdt, Jan Östergren, Gianfranco Parati, Joep Perk, Jorge Polónia, Bogdan A. Popescu, Zeljko Reiner, Lars Rydén, Yuriy Sirenko, Alice Stanton, Harry A.J. Struijker-Boudier, Charalambos Vlachopoulos, Massimo Volpe, David A. Wood 
TL;DR: In this article, a randomized controlled trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly people was presented. But the authors did not discuss the effect of the combination therapy in patients living with systolic hypertension.
Abstract: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

14,173 citations

Journal ArticleDOI
TL;DR: 2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the management of Arterspertension of the European Society ofhypertension (ESH) and of theEuropean Society of Cardiology (ESC).
Abstract: Because of new evidence on several diagnostic and therapeutic aspects of hypertension, the present guidelines differ in many respects from the previous ones. Some of the most important differences are listed below: 1. Epidemiological data on hypertension and BP control in Europe. 2. Strengthening of the prognostic value of home blood pressure monitoring (HBPM) and of its role for diagnosis and management of hypertension, next to ambulatory blood pressure monitoring (ABPM). 3. Update of the prognostic significance of night-time BP, white-coat hypertension and masked hypertension. 4. Re-emphasis on integration of BP, cardiovascular (CV) risk factors, asymptomatic organ damage (OD) and clinical complications for total CV risk assessment. 5. Update of the prognostic significance of asymptomatic OD, including heart, blood vessels, kidney, eye and brain. 6. Reconsideration of the risk of overweight and target body mass index (BMI) in hypertension. 7. Hypertension in young people. 8. Initiation of antihypertensive treatment. More evidence-based criteria and no drug treatment of high normal BP. 9. Target BP for treatment. More evidence-based criteria and unified target systolic blood pressure (SBP) (<140 mmHg) in both higher and lower CV risk patients. 10. Liberal approach to initial monotherapy, without any all-ranking purpose. 11. Revised schema for priorital two-drug combinations. 12. New therapeutic algorithms for achieving target BP. 13. Extended section on therapeutic strategies in special conditions. 14. Revised recommendations on treatment of hypertension in the elderly. 15. Drug treatment of octogenarians. 16. Special attention to resistant hypertension and new treatment approaches. 17. Increased attention to OD-guided therapy. 18. New approaches to chronic management of hypertensive disease

7,018 citations

Journal ArticleDOI
TL;DR: Current evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion, which is presented in detail in this review.
Abstract: The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

5,514 citations

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TL;DR: The vascular endothelium is an active paracrine, endocrine, and Endothelial cell infection and endotheliitis in COVID-19 and recruitment of immune cells can result in widespread endothelial dysfunction associated with apoptosis.

4,855 citations

Journal ArticleDOI
TL;DR: Since 1980, the American College of Cardiology and American Heart Association have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health.
Abstract: Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health. In 2013, the National Heart, Lung, and Blood Institute (NHLBI) Advisory

4,604 citations