Cerbai, Elisabetta

Failli, Paola

Franchi Micheli, S.

Mugelli, Alessandro

Raimondi, Laura

English

Florence Research

month-old PHT. This study showed that the early develop-ment of vascular dysfunction in the endothelial cells as wellas vascular smooth muscle cells in PHT rabbits. These resultssuggest that post-prandial hypertriglyceridemia may becomean important risk factor for promoting atherosclerosis.Keywords: Endothelium; Metabolism; Smooth muscledoi:10.1016/j.yjmcc.2007.03.691Losartan ameliorates diabetic vascular hyper-reactivity toangiotensin II by reducing ROCK1 expression and activityLaura Raimondi, Sergio Franchi-Micheli, Elisabetta Cerbai,Alessandro Mugelli, Paola Failli. Department of Pharmacology,University of Florence, ItalyWe investigated the effect of an in vivo treatment withlosartan, an angiotensin type 1 receptor antagonist (ARB), onthe angiotensin II (ATII) contracture elicited in phenylephrinepre-contracted aortic strips isolated from normo (groups Aand B) and hyperglycemic rats (STZ injected, 55 mg/kg;group C and D) not treated (groups A and C) and treatedwith losartan (20 mg kg−1 day−1; groups B and D). WhileATII showed similar E50 values in all the preparationstested, its maximum effect (expressed as % of maximumphenylephrine contraction) reached 360% in group C, 250%in group D and only 175% in groups A and B. Aortas fromall the animal groups responded similarly to irbesartan, anARB, added to superfusion medium (50% reduction of theATII maximum effect). The ATII contracture in groups Cand D were reduced (32% and 22% respectively) by fasudil,an inhibitor of the RhoA/ROCK1 pathway. Exposure to thesame drug left unchanged the ATII contracture in the aortasfrom groups A and B. ROCK1 enzyme activity (mU/mg oftissue proteins) was 0.04±0.01 in normoglycemic, 1.42±0.22* (p<0.001 vs. groups A and B) in diabetic aortas andonly 0.72±0.05§ (§p<0.05 vs. groups A and B) in theaortas from losartan-treated diabetic rats.In diabetes, ROCK1 overexpression is functionally coupledwith aorta hyper-reactivity towards ATII. We provide evidencestating that losartan ameliorates vascular response to ATIIreducing ROCK1 activity and expression.Keywords: Diabetes mellitus; Renin angiotensin system;Pharmacologydoi:10.1016/j.yjmcc.2007.03.692Synthetic flavonol preserves postischemic endothelialfunction after 7 days reperfusion in conscious sheepSheng Wang, Colleen J. Thomas, Greg J. Dusting, Owen L.Woodman, Clive N. May. Howard Florey Institute andMelbourne University, AustraliaMyocardial ischemia–reperfusion impairs endothelium-de-pendent dilatation due to oxidative stress. The syntheticflavonol, 3′,4′-dihydroxyflavonol (DiOHF), is an effectiveantioxidant which reduces infarct size. This study inconscious, instrumented sheep subjected to experimentalmyocardial infarction investigated the ability of DiOHF topreserve post-ischemic coronary endothelial function. Acet-ylcholine (ACh, 10 μg/kg/min iv) increased coronaryconductance (CC) before ischemia (ΔCC, ACh, 34±4%). Invehicle-treated sheep (n=4) following prolonged (1 h)ischemia and 24 h reperfusion, vasodilatation of the coronaryvascular bed to ACh was significantly reduced (ΔCC, 7±2%). p<0.05). This impairment of endothelial functionpersisted even after 7 days of reperfusion (ΔCC 15±2%).In DiOHF-treated sheep (2 mg/kg i.v. bolus 5 min beforereperfusion, n=4), however, coronary vasodilatation inresponse to acetylcholine was partly preserved after 24 h ofreperfusion (ΔCC 18±5% n.s.) and completely recovered(ΔCC 31±7% n.s.) after 7 days of reperfusion. Animals inboth groups maintained vascular responses to SNP duringreperfusion, confirming normal function of vascular smoothmuscle. DiOHF also significantly decreased infarct sizeexpressed as a percentage of area at risk by approximately40% (vehicle=80±7%, DiOHF=46±11%). In conclusion,this study provides functional evidence that DiOHF protectsagainst endothelial dysfunction caused by ischemia andreperfusion.Keywords: Coronary endothelial dysfunction; Flavonol; Ische-mia–reperfusion injurydoi:10.1016/j.yjmcc.2007.03.693Endothelium-dependent prothrombotic and fibrinolyticfactors in patients with chronic heart failureK.A. Khmelnitskaya, E.V. Shlyakhto, M.U. Sitnikova. PavlovState Medical University, Almazov Research Institute ofCardiology, Saint-Petersburg, RussiaAlong with disturbance of blood flow, a hypercoagulablestate, endothelium plays an important regulatory role throm-boembolic pathophysiology and produces prothrombotic andantithrombotic factors in the chronic heart failure (CHF). In studywe have investigated endothelial-dependent hemostasis [vonWillebrand factor (vWf), tissue plasminogen activator (tPA)] andendothelial damage [circulating endothelial cells (CECs), anindex of endothelial damage] in 108 patients with ischemic heartdisease and CHF I–IV class (NYHA), who were compared with30 age-matched patients with ischemic heart disease withoutCHF and 27 age-matched healthy control subjects.Results: There was an increase plasma levels CECs in pa-tients with CHF compared without CHF (p=0.002) and healthycontrols (p=0.001). Patients with more severe symptoms CHF(class III–IV) had higher CECs (p=0.01), vWf (p=0.02), lowertPA-antigen (p=0.1), than class I–II. A significant increaseS230 ABSTRACTS / Journal of Molecular and Cellular Cardiology 42 (2007) S219–S233

Losartan ameliorates diabetic vascular hyper-reactivity to angiotensin II by reducing ROCK1 expression and activity

https://flore.unifi.it/bitstream/2158/778391/1/Raimondi2007.pdf

Losartan ameliorates diabetic vascular hyper-reactivity to angiotensin II by reducing ROCK1 expression and activity

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