Dong Yingying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 99-125). / Abstracts in English and Chinese. / Declaration --- p.i / Acknowledgement --- p.ii / Publication list --- p.iii / Abstract (English) --- p.ix / Abstract (Chinese) --- p.xii / Abbreviations --- p.xiv / List of figures / tables --- p.xvi / Chapter Chapter 1. --- General Introduction / Chapter 1.1 --- The role of endothelium in regulating vascular tone --- p.1 / Chapter 1.1.1 --- Nitric oxide (NO) --- p.2 / Chapter 1.1.2 --- Endothelium-derived hyperpolarizing factor (EDHF) --- p.7 / Chapter 1.1.3 --- Prostacyclin (PGI2) --- p.20 / Chapter 1.2 --- EDHF-mediated endothelial function in coronary circulation --- p.22 / Chapter 1.2.1 --- Role of EDHF in coronary microarteries --- p.23 / Chapter 1.2.2 --- Role of EDHF in cardiac veins --- p.24 / Chapter 1.3 --- Effect of ischemia-reperfusion on endothelial function in coronary circulation --- p.25 / Chapter 1.3.1 --- Ischemia-reperfusion injury --- p.26 / Chapter 1.3.2 --- Effect of ischemia-reperfusion on endothelial function in coronary microarteries --- p.28 / Chapter 1.3.3 --- Effect of ischemia-reperfusion on endothelial function in cardiac veins --- p.29 / Chapter 1.4 --- Alteration of endothelial function during cardiac surgery / Chapter 1.4.1 --- Cardioplegia and organ preservation solutions --- p.31 / Chapter 1.4.2 --- Combined effects of hypoxia-reoxygenation and ST solution on endothelial function in coronary microarteries/cardiac veins --- p.34 / Chapter 1.4.3 --- Effect of nicorandil on endothelial function --- p.34 / Chapter Chapter 2. --- Materials and Methods --- p.37 / Chapter 2.1 --- Isometric force study in micro arteries/veins --- p.37 / Chapter 2.1.1 --- Preparation of vessels --- p.37 / Chapter 2.1.1.1 --- Preparation of porcine coronary microarteries --- p.37 / Chapter 2.1.1.2 --- Preparation of porcine cardiac veins --- p.37 / Chapter 2.1.2 --- Technique of setting up --- p.39 / Chapter 2.1.2.1 --- Mounting of microvessels --- p.39 / Chapter 2.1.2.2 --- Normalization procedure for microvessels --- p.39 / Chapter 2.1.3 --- EDHF-mediated vasorelaxation --- p.40 / Chapter 2.1.3.1 --- Precontraction and stimuli of EDHF --- p.40 / Chapter 2.1.3.2. --- “Truéحresponse of EDHF --- p.40 / Chapter 2.1.4 --- Data acquisition and analysis --- p.41 / Chapter 2.2 --- Hypoxia and reoxygenation --- p.41 / Chapter 2.2.1 --- Calibration of 02-special electrode --- p.41 / Chapter 2.2.2 --- Measurement of --- p.02 / Chapter 2.3 --- Statistical analysis --- p.42 / Chapter 2.4 --- Chemicals --- p.43 / Chapter Chapter 3. --- Hypoxia-Reoxygenation in Coronary Microarteries: Combined Effect with St Thomas Cardioplegia and Temperature on the Endothelium- derived Hyperpolarizing Factor and Protective Effect of Nicorandil --- p.44 / Chapter 3.1 --- Abstract --- p.44 / Chapter 3.2 --- Introduction --- p.45 / Chapter 3.3 --- Experimental design and analysis --- p.47 / Chapter 3.3.1 --- Vessel Preparation --- p.47 / Chapter 3.3.2 --- Normalization --- p.48 / Chapter 3.3.3 --- Hypoxia --- p.48 / Chapter 3.3.4 --- Effect of H-R on EDHF-mediated relaxation in coronary microarteries --- p.49 / Chapter 3.3.5 --- Combined effects ofH-R and ST solution on EDHF-mediated relaxation in coronary microarteries --- p.49 / Chapter 3.3.6 --- Effect of addition of nicorandil Krebs or ST solution under H-R on EDHF-mediated relaxation in coronary microarteries --- p.49 / Chapter 3.3.7 --- Data analysis --- p.50 / Chapter 3.4 --- Results --- p.51 / Chapter 3.4.1 --- Resting force --- p.51 / Chapter 3.4.2 --- U46619-induced contraction force --- p.51 / Chapter 3.4.3 --- Partial pressure of oxygen in hypoxia --- p.51 / Chapter 3.4.4 --- EDHF-mediated relaxation in coronary microarteries --- p.51 / Chapter 3.4.4.1 --- Effect of H-R --- p.51 / Chapter 3.4.4.2 --- Combined effects ofH-R and ST solution on EDHF-mediated relaxation --- p.52 / Chapter 3.4.4.3 --- Effects of addition of nicorandil to Krebs or ST solution under H-R on EDHF-mediated relaxation --- p.52 / Chapter 3.5 --- Discussion --- p.53 / Chapter 3.5.1 --- EDHF-mediated relaxation after exposure to H-R --- p.53 / Chapter 3.5.2 --- EDHF-mediated relaxation after H-R in ST solution at different temperature --- p.54 / Chapter 3.5.3 --- Effect of addition of nicorandil to Krebs or ST solution during H-R on EDHF-mediated relaxation --- p.55 / Chapter 3.5.4 --- Clinical implications --- p.56 / Chapter Chapter 4. --- Hypoxia-Reoxygenation in Cardiac Microveins: Combined Effect with Cardioplegia and Temperature on the Endothelial Function --- p.68 / Chapter 4.1 --- Abstract --- p.68 / Chapter 4.2 --- Introduction --- p.69 / Chapter 4.3 --- Experimental design and analysis --- p.73 / Chapter 4.3.1 --- Vessel Preparation --- p.73 / Chapter 4.3.2 --- Normalization --- p.73 / Chapter 4.3.3 --- Hypoxia --- p.73 / Chapter 4.3.4 --- Effect of H-R on EDHF-mediated relaxation in cardiac micro veins --- p.74 / Chapter 4.3.5 --- Combined effects of H-R and ST solution on EDHF-mediated relaxation in cardiac microveins --- p.74 / Chapter 4.3.6 --- Data analysis --- p.75 / Chapter 4.4 --- Results --- p.75 / Chapter 4.4.1 --- Resting force --- p.75 / Chapter 4.4.2 --- U46619-induced contraction force --- p.76 / Chapter 4.4.3 --- Partial pressure of oxygen in hypoxia --- p.76 / Chapter 4.4.4 --- EDHF-mediated relaxation after H-R in Krebs solution at 37°C --- p.76 / Chapter 4.4.5 --- EDHF-mediated relaxation after exposure to H-R in ST solution at different temperatures --- p.77 / Chapter 4.5 --- Discussion --- p.78 / Chapter 4.5.1 --- Effect of H-R on EDHF-mediated relaxation --- p.78 / Chapter 4.5.2 --- Combined effects of H-R with ST solution on EDHF-mediated relaxation --- p.80 / Chapter 4.5.3 --- Clinical implications / Chapter Chapter 5. --- General Discussion --- p.89 / Chapter 5.1 --- EDHF-mediated endothelial function in porcine coronary circulation --- p.89 / Chapter 5.1.1 --- EDHF in porcine coronary microarteries --- p.92 / Chapter 5.1.2 --- EDHF in porcine cardiac veins --- p.90 / Chapter 5.2 --- Alteration of EDHF-mediated function after exposure to H-R --- p.91 / Chapter 5.2.1 --- In coronary microarteries --- p.91 / Chapter 5.2.2 --- In cardiac veins --- p.92 / Chapter 5.3 --- Alteration of EDHF-mediated function after exposure to ST solution under H-R --- p.92 / Chapter 5.3.1 --- In coronary microarteries --- p.93 / Chapter 5.3.2 --- In cardiac veins --- p.93 / Chapter 5.4 --- EDHF-mediated function in nicorandil-supplemented ST solution under H-R in coronary microarteries --- p.93 / Chapter 5.5 --- Clinical implications / Chapter 5.5.1 --- H-R injury --- p.94 / Chapter 5.5.2 --- H-R injury and cardioplegic solution --- p.95 / Chapter 5.5.2 --- Nicorandil-supplementation in cardioplegic solution --- p.95 / Chapter 5.6 --- Limitation of the study --- p.96 / Chapter 5.7 --- Future investigations --- p.96 / Chapter 5.8 --- Conclusions --- p.97 / References --- p.99

Chronic treatment with enalapril and valsartan significantly improved endothelium-dependent relaxations of aortas from ovariectomized rats. The present results clearly point to that chronic treatment with enalapril or valsartan reduced expression and function of RAS and associated oxidative stress, thereby augmented NO bioavailability and improved endothelium-dependent relaxations. These results provided novel evidence supporting a potential application of ACEI and ARB in the treatment of endothelial dysfunction-associated vascular complications in postmenopausal women. / Functional studies showed that acetylcholine-induced relaxations in isolated aortas were impaired in a time-dependent manner, from the 4th-week to the 12th-week after ovariectomy. The impaired relaxations were partially restored by acute treatment with losartan [angiotensin II type 1 receptor (AT1R) blocker] and apocynin [NAD(P)H oxidase inhibitor]. The present results demonstrate that estrogen deficiency blunted endothelium-dependent relaxations due to impaired the NO bioavailability, which is closely associated with the reduced eNOS activity and elevated RAS expression and associated NAD(P)H oxidase-mediated oxidative stress in the vascular wall. / The present study shows that chronic consumption of cranberry juice restored the endothelium-dependent relaxations in aortas from ovariectomized rats. In ovariectomized rats, the phenylephrine-induced a higher active vascular tension; which was prevented by chronic consumption of cranberry juice. The present data also shows that cranberry juice administration significantly reduces the elevated serum levels of total cholesterol, triglyceride, high density lipoprotein (HDL) cholesterol, non-HDL (nHDL) cholesterol, and nHDL/HDL. The active ingredients in the cranberry juice organic extract accounting for the vascular benefit remain to be further examined even though the extract causes endothelial NO-dependent relaxations in normal rat aortas and contains several bioactive compounds, some of which may protect the vascular function. This study provides the first line of evidence concerning a significant vascular benefit of chronic consumption of cranberry juice during estrogen deficiency. (Abstract shortened by UMI.) / The present study used ovariectomized female rats that mimic the "equivalent" state of menopause in human and investigated whether dysregulation of RAS components contribute to endothelial dysfunction and whether chronic treatment with ACEI (enalapril) or ARB (valsartan) could restore endothelial function in ovariectomized rats. / The second objective of the present study was to investigate whether or not consumption of cranberry juice, a popular drink in Western countries, could restore endothelial function during estrogen deficiency and to elucidate the cellular mechanisms underlying the improved endothelial function. / Yung, Lai Ming. / Adviser: Huana Yu. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3252. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 148-168). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Zhang Rongzhen. / "July 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 130-176). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Introduction: Idiopathic Pulmonary arteriole hypertension (IPAH) is a rare but severely debilitating disease that strikes women to men at a ratio of 3:1. Endothelial cell (EC) dysfunction is a hallmark of the disease. This includes rapid growth of the ECs until the occlusion of the vasculature as well as decreased blood levels of vasodilators. Markedly increased levels of endothelin-1, a potent vasoconstrictor and smooth muscle mitogen, have been noted in IPAH patients. / Recently mutations in the bone morphogenic protein receptor type II (BMPRII) have been linked to the disease. Interestingly mutations in activin-like kinase-1 (ALK-1) and endoglin have been linked to hereditary haemorrhagic telangiectasia (HHT), a disease that results in PAH clinically indistinguishable from IPAH. All of these proteins are either receptors or co-receptors to members of the TGFbeta superfamily. The connection of these mutations to the disease still remains largely a mystery to researchers and the effects of either bone morphogenic proteins 2, 4, 7 or TGFbeta levels on endothelin-1(ET-1) production in human microvascular endothelial cells cultured from normal lungs (HMVEC-LBI) are unknown. / Methods: HMVEC-LBI cells were cultured in the presence of various concentrations of BMP 2,4,7 and TGFbeta, in complete media or serum starved conditions. After allotted time points the media was collected and assayed by ELISA, meanwhile the cells were lysed and protein content assayed for normalization purposes. Small Mothers against Decapentaplegic (SMAD) 1/5 phosphorylation was also measured. / Results and Conclusions: Despite evidence that all BMPs used were biologically active, namely through SMAD phosphorylation studies, only BMP7 at very high dosages increased ET-1 production levels. TGFbeta had a more pronounced effect at earlier time points with lower concentrations. The results provide insights on the effects of an important group of proteins, the BMPs and TGFbeta, on lung microvascular ECs and which are likely the key cellular player In IPAH development. These findings may have clinical relevance in terms of control of the disease and understanding the normal response of these cells BMPs and TGFbeta.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Apesar dos grandes avanços na medicina perioperatória, as operações vasculares ainda estão associadas a elevada morbi-mortalidade. A fisiopatologia dos eventos perioperatórios é complexa, envolvendo a instabilização de placas ateroscleróticas, o que não é contemplado nos algoritmos para estratificação de risco cardíaco perioperatório. Acreditamos que a identificação de características relacionadas à instabilização de placas incipientes, como alterações na reatividade vascular e maior atividade inflamatória, pode melhorar a acurácia da estimativa de risco e a análise do comportamento perioperatório destas características pode elucidar importantes mecanismos fisiopatológicos. Estudamos 100 pacientes com indicação de operação vascular e aferimos por meio de ultrassom-Doppler de artéria braquial, a hiperemia reativa (HR), marcador de função microvascular, e a dilatação mediada pelo fluxo (DMF), marcador de função endotelial, antes e após a operação. Analisamos também os níveis de proteina-C reativa ultra-sensível (PCR-us). A operação foi realizada em 96 pacientes e 27 deles apresentaram algum evento até o 30º dia pós-operatório: 4 óbitos cardíacos, 5 infartos agudos do miocárdio, 2 acidentes vasculares cerebrais isquêmicos, 2 elevações isoladas de troponina, 1 embolia de pulmão, 2 reoperações e 11 óbitos não cardíacos. Detectamos disfunção endotelial em 70% dos pacientes, mas não observamos nenhum padrão característico de comportamento perioperatório da DMF, ou associação significativa entre a mesma e os eventos. Observamos significativo aumento da PCR-us após a intervenção cirúrgica (0,5mg/dL x 3,01mg/dL, P=0,001), mas sem associação com eventos. Identificamos forte associação entre disfunção microvascular, representada pela menor velocidade de fluxo na artéria braquial durante a hiperemia reativa, e eventos: 81 cm/s + 20 x 95 cm/s + 28 ( P= 0,02). Concluímos que a identificação de disfunção microvascular no pré-operatório pode estratificar o risco de complicações perioperatórias e que embora não tenhamos observado piora da vasodilatação mediada pelo fluxo, não podemos afastar que haja piora da função endotelial no perioperatório. O aumento de PCR-us denota grande diátese inflamatória, que pode estar relacionada à disfunção endotelial. / Despite great advances in perioperative care, major vascular surgeries are still related to high morbidity and mortality. The pathophysiology of perioperative cardiac events is complex and comprehends atherosclerotic plaque instability, witch is not contemplated in the current algorithms for cardiac risk estimation. We hypothesized that the identification of characteristics related to predisposition for plaque instability, such as abnormalities in the vascular reactivity, is very promising and the characterization of this parameter`s behavior in the perioperative setting contributes to the better understanding of event\'s pathophysiology. We prospectively studied a cohort of 100 patients, candidates for elective major vascular surgery and assessed, by Doppler ultrasound in the brachial artery, reactive hyperemia(RH), a marker of microvascular function, and flow mediated dilation(FMD), a marker of endothelial function, before and after surgery. We also obtained C-reactive protein-high sensitive assay (CRP-hs) before and after surgery. Ninety six patients were submitted to the planned vascular surgery and 27 patients had an event up to the 30º postoperative day. We observed 4 cardiac deaths, 5 acute myocardial infarctions, 2 isolated troponin elevations, 2 ischemic strokes, 1 pulmonary embolism, 2 reoperations and 11 noncardiac deaths. Results: although there was no significant difference in the preoperative FMD between patients with and without events: 4.83% + 6.81 x 5.88% + 6.00 (p= .457), respectively, low RH response, measured as lower peak flow velocity in RH, was associated to events: 81 cm/s + 20 x 95 cm/s + 28 (p=0,02). There was no significant difference in the preoperative CRP-hs between groups (median: 0.51mg/dL (IQR 2.12) x 0.41mg/dL (IQR 0.59), p= .234). There was no significant difference between FMD before and after surgery but we detected an almost 6-fold increase in CRP-hs after surgery: 0.50mg/dL x 3.01mg/dL (p < .001), respectively. Our study demonstrated that microvascular dysfunction is closely related to perioperative events after major vascular surgery and is a better marker of perioperative risk than endothelial dysfunction, in specific conditions.

A Trombomodulina é um marcador endotelial da doença aterosclerótica, e seu uso como preditor da doença arterial obstrutiva periférica (DAOP) deve ser comprovada. Avaliou-se 41 pacientes com claudicação intermitente e 40 com isquemia crítica. A Trombomodulina plasmática (TMp) foi quantificada em todos os pacientes, através de método imunoenzimático (ELISA). As hipóteses de normalidade e de homogeneidade de variância foram provadas, respectivamente, pelos testes de Shapiro-Wilk e de Levene. A comparação da TMp entre ambos os grupos foi realizada empregando-se o teste t de Student. A utilização de pacientes com Claudicação Intermitente e com Isquemia Crítica é interessante como modelo de estudo e deve ser empregado para avaliar diferentes marcadores de prognóstico da DAOP. Não foi observada diferença estatisticamente significante nos níveis de TMp nos grupos, não permitindo utilizar-se a TMp para avaliar o prognóstico da doença arterial obstrutiva periférica (DAOP) / Thrombomodulin (TM) is an endothelial marker of arterosclerotic disease and its use as a predictor of Peripheral Arterial Disease (PAD) must be proven. Forty-one patients having intermittent claudication and forty having critical ischemia were evaluated. Plasmatic Thrombomodulin (TMp) was quantified in all patients using the immunoenzymatic method (ELISA). The hypotheses of normality and variance homogeneity were proven, respectively, using the Wilk-Shapiro and Levene Tests. The comparison of the TMp between both groups was carried out using the Student-T Test. The utilization of patients with Intermittent Claudication and Critical Ischemia is interesting as a study model and should be used to evaluate different prognostic markers of PAD. No statistically significant difference was observed in the TMp levels between the groups, thus not permitting the use of TMp to evaluate the prognostics of Peripheral Arterial Disease (PAD)

Introdução: A hipertensão arterial sistêmica (HA) pode estar associada à diminuição na produção e liberação do óxido nítrico derivado do endotélio (NO). O uso do sildenafil leva ao aumento de monofosfato de guanosina cíclica (GMPc), um importante mediador de NO. Contudo, pouco se sabe sobre os efeitos da inibição da fosfodiesterase tipo 5 (PDE5) na monitorização da pressão arterial 24-h (MAPA), pressão arterial durante exercício, noraepinefrina (Nor) e capacidade ao exercício, principalmente após transplante de coração (TX). Métodos: Nós estudamos 22 pacientes pós TX, os quais foram randomizados, tomando dose única de sildenafil (50mg) ou placebo (50mg), aproximadamente uma hora antes de iniciar o protocolo. No dia 1, os pacientes realizaram avaliação clínica, teste cardiopulmonar de caminhada de seis minutos (TES) seguido de teste de esforço cardiopulmonar (TE), Após o término dos testes em esteira, foi colocado o MAPA. Determinamos em repouso (rep), último minuto do TES (6) e pico do TE (Ex): FC (bpm) PAS e PAD (mmHg), VO2(ml/kg/min), Slope VE/VCO2, tempo de exercício (TE, min), distância (TES, Km) e Nor (pg/ml). No dia 2 o protocolo foi repetido, realizando-se o cross-over. Dezessete pacientes apresentavam HA. Resultados: (Pl e Sil respectivamente), Sil reduziu (p<0.05): PAS-rep(138±7 vs 122±18); PAD-rep(83±12 vs 78±12); PAS-6(156± 20 vs 137± 22); PAD-6(82±13 vs 77±14); PAS-Ex(155± 27vs 124±36); PAD-Ex(79±16 vs 66± 16); PAS 24-h(121±10 vs 114±9), PAD 24-h(80±6 vs 76±5), PAS vigília(122±11 vs 115±9), PAD vigília(81± 6 vs 76±5) e PAS noturna(119±12 vs 112±10), PAD noturna(78±7 vs 73±8); e aumentou Nor-repouso(483±165 vs 622±211). Sil não alterou rep, 6 e EX: FC, VO2 e Slope. Conclusão: O ciclo NO-cGMP parece desempenhar papel importante no controle da pressão arterial em TX. Sendo que, a inibição da PDE5 parece apresentar efeitos benéficos no controle da hipertensão arterial em TX, podendo ser utilizada concomitantemente a terapia anti-hipertensiva usual. / Background: Systemic hypertension (SH) can be associated with a decrease in endothelium-dependent nitric oxide (NO). Sildenafil determines increment in cyclic guanosine monophosphate (cGMP) that a mediator of NO. However, little is known about the effects of PDE5 inhibition on 24-hour ambulatory (ABP) and exercise blood pressure, noreprinephrine (Nor) and exercise capacity, specially after heart transplantation (HT). Methods: We studied 22 HT pts that on the 1st day underwent a cardiopulmonary (CP) self-controlled treadmill 6walk test(6) and, after, an ECG monitored CP treadmill maximal exercise test(Ex) within 60 and 90 min after oral Sildenafil (Sil,50mg) or placebo(Pl) given at random, and ABP. We determined at basal position(b), last min of 6 and the peak Ex the HR(bpm), SBP and DBP (mmHg), VO2(ml/kg/min), Slope VE/VCO2, exercise time(ET, min), distance(D, Km) and Nor(pg/ml). Also, after CP tests 24-h SBP and DBP were monitored. It was repeated on the 2nd day when the cross-over was done. Seventeen pts had SH. Results: (Pl and Sil respectively), Sil reduced (p<0.05): b- SBP(138±7 vs 122±18); b-DBP(83±12 vs 78±12); 6-SBP(156± 20 vs 137± 22); 6-DBP(82±13 vs 77±14); Ex-SBP(155± 27vs 124±36); Ex-DBP(79±16 vs 66± 16); 24-h SBP(121±10 vs 114±9) and DBP(80±6 vs 76±5), daytime SBP(122±11 vs 115±9) and DBP(81± 6 vs 76±5) and nighttime SBP(119±12 vs 112±10) and DBP(78±7 vs 73±8); and increase b-Nor(483±165 vs 622±211). Sil did not change in b, 6 and EX; HR, Nor, VO2 and Slope. Conclusion: NO-cGMP pathway seems to play a role in blood pressure control in HT. The PDE5 inhibition could have potential beneficial effects on hypertensive HT in addition to antihypertensive therapy.

Pacientes sépticos podem evoluir para choque séptico, destes 40% sobrevivem. Caracterizamos o modelo experimental, avaliamos fatores envolvidos na inflamação e avaliamos a modulação causada por purinas (ATP/ADP) na quantificação de superóxido (O2-) e na reatividade vascular da aorta isolada. Os resultados sugerem que na aorta isolada de animais endotoxêmicos, ATP e ADP aumentam a síntese de óxido nítrico (NO), porém somente o ATP reduz a biodisponibilidade de O2-, provavelmente pelo reacoplamento da NO sintase endotelial / Septic patients can evolve for septic shock and 40% of these survive. We characterize the experimental model we evaluate involved factors in the inflammation and evaluate the modulation caused by purines (ATP/ADP) in the superoxide quantification (O2-) and in the vascular reactivity of isolated aorta. The results suggest that in isolated aorta of endotoxemics rats, ATP and ADP increase the endothelial nitric oxide synthase (NOS) however just ATP reduces the bio availability of O2-, probably for the re-couples of the endothelial NOS synthase

Introdução: O aumento da massa ventricular esquerda e a disfunção endotelial são importantes fatores de risco cardiovascular em hipertensos e normotensos. Estudos investigando a associação entre massa ventricular esquerda e disfunção endotelial, utilizando diversas metodologias, são contraditórios. A tonometria arterial periférica (PAT) é um método não invasivo, validado e reprodutível que permite analisar simultaneamente além da função endotelial, outros aspectos da função vascular, como a amplitude de pulso basal (BPA), que reflete o tônus vascular basal, e a contribuição da reflexão da onda de pulso (PAT-AIx). Estas características podem colaborar para a compreensão da associação entre massa ventricular esquerda e função endotelial em hipertensos. Objetivo: Analisar a correlação entre a função endotelial, obtida pela PAT, e a massa ventricular esquerda, em pacientes com hipertensão arterial sistêmica, com e sem hipertrofia ventricular esquerda (HVE). Métodos: Em estudo transversal, foi avaliada a associação entre massa ventricular esquerda e função endotelial em 46 pacientes hipertensos ambulatoriais do Hospital da Universidade Federal do Ceará, com idade de 40 a 60 anos e pressão arterial menor que 180/110mmHg, sem outros FRCV. Todos os pacientes realizaram avaliação clínica e laboratorial, ecocardiograma e PAT. HVE foi definida como índice de massa ventricular esquerda (IMVE) > 48 g/m2,7 para homens e > 44 g/m2,7 para mulheres. Através da PAT, foram medidos o índice de hiperemia reativa (RHI), a razão PAT (PAT ratio), o PAT-AIx e a BPA. Correlação entre variáveis contínuas foi estimada através do Coeficiente de Correlação de Pearson ou Spearman. Comparações de distribuições de variáveis contínuas foram realizadas através do Teste t Student ou do Teste da Soma dos Postos de Mann-Whitney. Proporções foram comparadas através do Teste Exato de Fisher. Resultados de comparações foram considerados significativamente diferentes quando o valor-p foi < 0,05. A associação entre massa ventricular esquerda e função endotelial foi avaliada através de regressão linear ou regressão logística. Resultados: Houve correlação significativa do IMVE (g/m2,7) com PAT-AIx (r= 0,304; p=0,043), com RHI (r=0,321; p= 0,046) e com PAT ratio (r=0,347; p=0,03). Esta associação foi independente de confundidores. Dezoito pacientes (39,1%) apresentavam HVE. Dentre os índices de função vascular, apenas a PAT-AIx diferiu entre os pacientes com e sem HVE (p=0,025), sendo os maiores valores encontrados no grupo com HVE. A presença de HVE foi associada ao PAT-AIx (razão de chances= 2,804 [1,29]; p=0,025), mas não foi associada com os demais índices de função vascular, independente de confundidores. Onze pacientes (23,9%) não usavam anti-hipertensivos; neste grupo, o IMVE (g/m2,7) foi associado ao RHI (coef=10,64 [3,11]; p=0,009) e ao PAT ratio (coef=22,85 [7,29]; p=0,014). Conclusão: Em hipertensos de grau leve a moderado, o índice de massa ventricular esquerda (g/m2,7) tem correlação positiva com a função endotelial digital e com o PAT-AIx. A associação independe do uso de anti-hipertensivos e dos níveis pressóricos / Background: Increased left ventricular mass and endothelial dysfunction are important cardiovascular risk factors in hypertensive and normotensive. Studies investigating the association between left ventricular mass and endothelial dysfunction, using different methodologies, are contradictory. Peripheral arterial tonometry (PAT) is a noninvasive, reproducible and validated method which allows simultaneously analyze endothelial function in addition other aspects of vascular function, as the basal pulse amplitude (BPA), which reflects the basal vascular tone, and contribution of the pulse wave reflection (PAT-AIx). These characteristics may contribute to the understanding of the association between endothelial function and left ventricular mass in hypertensive. Objective: To analyze the correlation between endothelial function obtained with the PAT in patients with hypertension, with and without left ventricular hypertrophy (LVH). Methods: In a cross-sectional study, we evaluated the association between endothelial function and left ventricular mass in 46 outpatient hypertensive patients of the Walter Cantídio Universitary Hospital, Federal University of Ceara, Brazil, aged 40-60 years and blood pressure under 180 / 110mmHg, no other CVRF. All patients underwent clinical and laboratory evaluation, echocardiography and PAT. LVH was defined as left ventricular mass index (LVMI) > 48 g / m2.7 for men and > 44 g / m2.7 for women. By PAT, were measured reactive hyperemia index (RHI), the PAT ratio, the PAT-AIx and the BPA. Correlation between continuous variables was estimated using the Pearson or Spearman correlation coefficient. Student\'s t-tests or Wilcoxon\'s rank sum test (Mann-Whitney) were used to examine differences between the groups in normally distributed or not-normally-distributed continuous variables, respectively. Fisher exact test was used to examine the difference in proportions. A p value < 0.05 was considered statistically significant. Linear regression and logistic regression analysis were used to evaluate the association between left ventricular mass and endothelial function. Results: LVMI (g /m2.7) was positively associated with PAT-AIx (r = 0.304; p = 0.043), with RHI (r = 0.321; p = 0.046) and PAT ratio (r = 0.347; p = 0.03). This association was independent of confounders. Eighteen patients (39.1%) had LVH. Among the indices of vascular function, only the PAT-AIx differed between patients with and without LVH (p = 0.025), with higher values found in the group with LVH. The presence of LVH was associated with PAT-AIx (odds ratio = 2.804 (1.29); p = 0.025), but was not associated with other indices of vascular function, independent of confounders. Eleven patients (23.9%) did not use antihypertensive medication; in this group, LVMI (g / m2.7) was associated with RHI (beta coefficient (se) = 10.64 (3.11); p = 0.009) and the PAT ratio (beta coefficient (se) = 22.85 (7.29); p = 0.014). Conclusion: In mild to moderate systemic hypertension, left ventricular mass index (g / m2.7) has positive correlation with digital endothelial function and the PAT-AIx. The association is independent of the use of antihypertensive medication and blood pressure levels