Nutritional Strategies for the Management of Type 2 Diabetes Mellitus: A Narrative Review.

BACKGROUND: Thinking about greater adherence to dietary planning, it is extremely important to be aware of all nutritional strategies and dietary prescriptions available in the literature, and of which of them is the most efficient for the management of T2DM. METHODS: A search was carried out in 2023 for randomized clinical trials, systematic reviews, meta-analyses, and guidelines in the following databases: Pubmed, Scielo, Web of Science, CrossRef and Google Scholar. In total, 202 articles were collected and analyzed. The period of publications was 1983-2023. RESULTS: There is still no consensus on what the best nutritional strategy or ideal dietary prescription is, and individuality is necessary. In any case, these references suggest that Mediterranean Diet may of greater interest for the management of T2DM, with the following recommended dietary prescription: 40-50% carbohydrates; 15-25% proteins; 25-35% fats (<7% saturated, 10% polyunsaturated, and 10% monounsaturated); at least 14 g of fiber for every 1000 kcal consumed; and <2300 mg sodium. CONCLUSIONS: Individuality is the gold standard for dietary prescriptions, however, the Mediterranean diet with low levels of carbohydrates and fats seems to be the most promising strategy for the management of T2DM.

Cardiovascular Autonomic Responses to Aerobic, Resistance and Combined Exercises in Resistance Hypertensive Patients.

Here, we report the acute effects of aerobic (AER), resistance (RES), and combined (COM) exercises on blood pressure, central blood pressure and augmentation index, hemodynamic parameters, and autonomic modulation of resistant (RH) and nonresistant hypertensive (NON-RH) subjects. Twenty participants (10 RH and 10 NON-RH) performed three exercise sessions (i.e., AER, RES, and COM) and a control session. Hemodynamic (Finometer®, Beatscope), office blood pressure (BP), and autonomic variables (accessed through spectral analysis of the pulse-to-pulse BP signal, in the time and frequency domain-Fast Fourrier Transform) were assessed before (T0), one-hour (T1), and twenty-four (T2) hours after each experimental session. There were no changes in office BP, pulse wave behavior, and hemodynamic parameters after (T0 and T1) exercise sessions. However, AER and COM exercises significantly reduced sympathetic modulation in RH patients. It is worth mentioning that more significant changes in sympathetic modulation were observed after AER as compared to COM exercise. These findings suggest that office blood pressure, arterial stiffness, and hemodynamic parameters returned to baseline levels in the first hour and remained stable in the 24 hours after the all-exercise sessions. Notably, our findings bring new light to the effects of exercise on RH, indicating that RH patients show different autonomic responses to exercise compared to NON-RH patients. This trial is registered with trial registration number NCT02987452.

Linear and non-linear analyses of autonomic modulation in uncontrolled and controlled elderly resistant hypertensives.

Resistant hypertension (RHT) is associated with worse outcomes among patients, and sympathetic overactivity is a challenge in treating this clinical condition. Here, we evaluated the autonomic modulation (by linear and non-linear analyses), central blood pressure, and pulse wave velocity in controlled and uncontrolled RHT patients, as well as those in use of beta-blockers. We observed that uncontrolled RHT patients display, in addition to an increase in peripheral blood pressure, presented higher central blood pressure values concerning controlled RHT. Furthermore, despite the use of beta-blockers, both patients in the RHT + beta-blockers and uncontrolled RHT groups had negative changes in autonomic balance as compared with controlled RHT. These results reinforce the importance of autonomic nervous system interventions in managing arterial hypertension.

Combined Aerobic and Resistance Exercises Evokes Longer Reductions on Ambulatory Blood Pressure in Resistant Hypertension: A Randomized Crossover Trial.

AIM: The present study compared the acute effects of aerobic (AER), resistance (RES), and combined (COM) exercises on blood pressure (BP) levels in people with resistant hypertension (RH) and nonresistant hypertension (NON-RH). METHODS: Twenty patients (10 RH and 10 NON-RH) were recruited and randomly performed three exercise sessions and a control session. Ambulatory BP was monitored over 24 hours after each experimental session. RESULTS: Significant reductions on ambulatory BP were found in people with RH after AER, RES, and COM sessions. Notably, ambulatory BP was reduced during awake-time and night-time periods after COM. On the other hand, the effects of AER were more prominent during awake periods, while RES caused greater reductions during the night-time period. In NON-RH, only RES acutely reduced systolic BP, while diastolic BP was reduced after all exercise sessions. However, the longest postexercise ambulatory hypotension was observed after AER (~11 h) in comparison to RES (~8 h) and COM (~4 h) exercises. CONCLUSION: Findings of the present study indicate that AER, RES, and COM exercises elicit systolic and diastolic postexercise ambulatory hypotension in RH patients. Notably, longer hypotension periods were observed after COM exercise. In addition, NON-RH and RH people showed different changes on BP after exercise sessions, suggesting that postexercise hypotension is influenced by the pathophysiological bases of hypertension.

Glycated hemoglobin correlates with arterial stiffness and endothelial dysfunction in patients with resistant hypertension and uncontrolled diabetes mellitus.

This study aimed to evaluate the effects of glycated hemoglobin (HbA1c ) on flow-mediated dilation, intima-media thickness, pulse wave velocity, and left ventricular mass index in patients with resistant hypertension (RHTN) comparing RHTN-controlled diabetes mellitus and RHTN-uncontrolled type 2 diabetes mellitus. Two groups were formed: HbA1c <7.0% (RHTN-controlled diabetes mellitus: n = 98) and HbA1c ≥7.0% (RHTN-uncontrolled diabetes mellitus: n = 122). Intima-media thickness and flow-mediated dilation were measured by high-resolution ultrasound, left ventricular mass index by echocardiography, and arterial stiffness by carotid-femoral pulse wave velocity. No differences in blood pressure levels were found between the groups but body mass index was higher in patients with RHTN-uncontrolled diabetes mellitus. Endothelial dysfunction and arterial stiffness were worse in patients with RHTN-uncontrolled diabetes mellitus. Intima-media thickness and left ventricular mass index measurements were similar between the groups. After adjustments, multiple linear regression analyses showed that HbA1c was an independent predictor of flow-mediated dilation and pulse wave velocity in all patients with RHTN. In conclusion, HbA1c may predict the grade of arterial stiffness and endothelial dysfunction in patients with RHTN, and superimposed uncontrolled diabetes mellitus implicates further impairment of vascular function.

O endotélio disfuncionante na hipertensão arterial e no tabagismo / Dysfunctional endothelium in hypertension and smoking

Disfunção endotelial (DE) caracteriza qualquer alteração de atividadenormal do endotélio incluindo atividade vasomotora, proliferaçãocelular, adesão/agregação plaquetária, permeabilidade vascular e a interaçãoleucócitos/parede vascular. Contudo, em repouso o leito arterialexibe um estado basal de vasoconstrição (tônus vascular) modulado pormecanismos de controle centrais (sistema nervoso-simpático), periféricos(sistema renina-angiotensina-aldosterona) e um mecanismo local(endotelial) cuja potência é superior às anteriores. DE na hipertensãoestá relacionada à diminuição da biodisponibilidade de NO por reduçãoda síntese e liberação pela sintase endotelial do óxido nítrico (eNOS)influenciada por fatores genéticos e ambientais como hipóxia, hipofluxo,forças de cisalhamento, redução do substrato L-arginina e seuscofatores, ou inativação do NO resultado da sua ligação com diferentesmoléculas hemoglobina, albumina e, principalmente, sua interação comespécies reativas de oxigênio (estresse oxidativo). DE na hipertensãopode, ainda, estar associada à liberação de substâncias vasoconstritorasderivadas do endotélio como trornboxano-Aç, prostaglândina-Hj,endotelina-l e angotensina-Il. Tabagismo aumenta o risco de eventoscardiovasculares, principalmente quando associado à hipertensão.Nicotina estimula a liberação de catecolarninas e promove lesões noendotélio vascular. Radicais livres e compostos aromáticos diminuema síntese de NO, prejudicando a vasodilatação endotélio-dependente.Tabagismo favorece o crescimento celular por estimulação de fatoresde crescimento do endotélio vascular e inativação do NO por aumentodo estresse oxidativo. Aumento da oxidação das lipoproteínas debaixa densidade (LDL) em fumantes tem efeito sinérgico na adesão emigração de monócitos. Todos esses efeitos deletérios do tabagismono leito vascular também são observados, embora em menor extensão,em tabagistas passivos...

Endothelial dysfunction (ED) characterizes ali changes in the normalactivity ofthe endothelium including vasomotor activity, cell proliferation,platelet adhesion and aggregation, vascular permeability andleukocyte-vascular wall interactions. However, at rest, the arterialbed exhibits a baseline state of vasoconstriction (vascular tone) whichis modulated by central control (sympathetic nervous system) andperipheral mechanisms (Renin angiotensin-aldosterone system) anda local mechanism (endothelial); the latter is the most potent. ED inhypertension is related to decreased bioavailability of nitric oxide(NO) due to its reduced synthesis and release by endothelial nitricoxide synthase (eNOS) regarding genetic and environmental factorssuch as hypoxia, decreased blood flow, shear forces, diminishedL-arginine substrate and its cofactors and NO inactivation as a resultof its binding to different molecules including hemoglobin, albuminand, mainly, its interaction with reactive oxygen species (oxidativestress). ED in hypertension can also be linked to the release of endothelium-derived vasoconstricting substances such as thromboxane-Ai,prostaglandin-H2, endothelin-l and angiotensin-Il. Smoking increasesthe risk of cardiovascular events especially when associated withhypertension. Nicotine stimulates catecholamine release and causesvascular endothelium injury. Free radicais and aromatic compoundsreduce NO synthesis, impairing endothelium-dependent vasodilation.Smoking promotes cell growth by stimulating vascular endotheliumgrowth factors and NO inactivation by increasing oxidative stress.The increased oxidation of low-density lipoproteins ir smokers hasa synergistic effect on monocyte adhesion and migration. All thesedeleterious effects of smoking on the vascular bed are also observed,albeit at a lesser extent, in passive smokers...

Infliximab reduces cardiac output in rheumatoid arthritis patients without heart failure.

OBJECTIVE: Human anti-tumor necrosis factor (TNF-α) monoclonal antibody (infliximab) is used to treat autoimmune diseases such as rheumatoid arthritis (RA). Although the risk of worsening heart failure has been described in patients under chronic treatment, the acute cardiovascular effects of this drug are unknown in RA patients without heart failure. METHODS: 14 RA patients with normal echocardiography and no history of heart failure were evaluated during the 2-hour infliximab (3-5 mg/kg) infusion period, using a noninvasive hemodynamic beat-to-beat system (Portapres). Stroke volume (SV); systolic, diastolic and mean blood pressures (SBP, DBP and MBP, respectively); cardiac output (CO); heart rate (HR); and total peripheral vascular resistance (PVR) were recorded. All patients also received saline infusion instead of infliximab as a control. Significant differences in hemodynamic parameters were determined using Tuckey's test. All values were expressed as mean ± standard deviation (SD). RESULTS: Fourteen RA patients (6M/8F) with mean age of 47.2 ± 8.8 years were evaluated. A significant decrease was found in cardiac output and stroke volume (7.04 ± 2.3 to 6.12 ± 2.1 l/min and 91 ± 29.0 to 83 ± 28.8 mL/beat, respectively) after infliximab infusion. Although not statistically significant, a progressive increase was detected in SBP, DBP and total PVR during infusion. Saline infusion did not cause significant hemodynamic changes in the same group of RA patients. No adverse effects were observed during the infusion period. CONCLUSION: Acute infliximab administration decreased cardiac output due to low stroke volume in RA patients without heart disease. The results also demonstrated that, in spite of its negative inotropic effect, infliximab enhanced BP, probably by increasing PVR.

Infliximab reduces cardiac output in rheumatoid arthritis patients without heart failure / Infliximabe reduz débito cardíaco em pacientes com artrite reumatoide sem insuficiência cardíaca

OBJECTIVE: Human anti-tumor necrosis factor (TNF-α) monoclonal antibody (infliximab) is used to treat autoimmune diseases such as rheumatoid arthritis (RA). Although the risk of worsening heart failure has been described in patients under chronic treatment, the acute cardiovascular effects of this drug are unknown in RA patients without heart failure. METHODS: 14 RA patients with normal echocardiography and no history of heart failure were evaluated during the 2-hour infliximab (3-5 mg/kg) infusion period, using a noninvasive hemodynamic beat-to-beat system (Portapres). Stroke volume (SV); systolic, diastolic and mean blood pressures (SBP, DBP and MBP, respectively); cardiac output (CO); heart rate (HR); and total peripheral vascular resistance (PVR) were recorded. All patients also received saline infusion instead of infliximab as a control. Significant differences in hemodynamic parameters were determined using Tuckey's test. All values were expressed as mean ± standard deviation (SD). RESULTS: Fourteen RA patients (6M/8F) with mean age of 47.2 ± 8.8 years were evaluated. A significant decrease was found in cardiac output and stroke volume (7.04 ± 2.3 to 6.12 ± 2.1 l/min and 91 ± 29.0 to 83 ± 28.8 mL/beat, respectively) after infliximab infusion. Although not statistically significant, a progressive increase was detected in SBP, DBP and total PVR during infusion. Saline infusion did not cause significant hemodynamic changes in the same group of RA patients. No adverse effects were observed during the infusion period. CONCLUSION: Acute infliximab administration decreased cardiac output due to low stroke volume in RA patients without heart disease. The results also demonstrated that, in spite of its negative inotropic effect, infliximab enhanced BP, probably by increasing PVR.

OBJETIVO: O inibidor de fator de necrose tumoral (TNF-α) infliximabe é usado no tratamento de doenças autoimunes como a artrite reumatoide (AR). Embora o risco de piora de insuficiência cardíaca em pacientes submetidos a tratamento crônico tenha sido descrito, os efeitos cardiovasculares agudos da infusão desta droga em pacientes com AR sem insuficiência cardíaca são desconhecidos. MÉTODOS: Pacientes com AR e ecocardiogramas normais e sem antecedentes de insuficiência cardíaca foram avaliados durante o período de infusão de infliximabe (3-5mg/kg), de 2 horas, utilizando um sistema de monitoramento hemodinâmico não invasivo batimento-a-batimento (Portapres). As variáveis avaliadas foram: volume sistólico (VS), pressão arterial sistólica, diastólica e média (PAS, PAD e PAM, respectivamente), débito cardíaco (DC), frequência cardíaca (FC) e resistência vascular periférica total (RVPT). Todos os voluntários também receberam infusão de soro fisiológico (SF) como estudo controle. Estatísticas foram avaliadas usando o teste de Tuckey. Os valores estão expressos em média ± desvio-padrão. RESULTADOS: Catorze pacientes (6M/8F), com idade média de 47,2 ± 8,8 anos, foram avaliados. Reduções significativas no débito cardíaco e volume sistólico foram encontradas após a infusão do infliximabe (7,04 ± 2,3 a 6,12 ± 2,1 L/min e 91 ± 29,0 a 83 ± 28,8 mL/batimento, respectivamente). Embora não estatisticamente significante, detectaram-se aumentos progressivos na PAS, PAD e RVPT durante a infusão. A infusão controle de SF não causou mudanças hemodinâmicas significativas nos pacientes estudados. Não foram observados efeitos adversos no período de infusão. CONCLUSÃO: A administração de infliximabe reduz agudamente o débito cardíaco devido a redução no volume sistólico em pacientes com AR sem insuficiência cardíaca. Nossos resultados mostram que, apesar do efeito inotrópico negativo, o infliximabe elevou a pressão arterial, provavelmente devido ao aumento na RVPT.

Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles.

OBJECTIVES: We investigated the influence of sildenafil on cardiac contractility and diastolic relaxation and examined the distribution of phosphodiesterase-5 in the hearts of hypertensive rats that were treated with by NG-nitro-L-arginine methyl ester (L-NAME). METHODS: Male Wistar rats were treated with L-NAME and/or sildenafil for eight weeks. The Langendorff method was used to examine the effects of sildenafil on cardiac contractility and diastolic relaxation. The presence and location of phosphodiesterase-5 and phosphodiesterase-3 were assessed by immunohistochemistry, and cGMP plasma levels were measured by ELISA. RESULTS: In isolated hearts, sildenafil prevented the reduction of diastolic relaxation (dP/dt) that was induced by L-NAME. In addition, phosphodiesterase-5 immunoreactivity was localized in the intercalated discs between the myocardial cells. The staining intensity was reduced by L-NAME, and sildenafil treatment abolished this reduction. Consistent with these results, the plasma levels of cGMP were decreased in the L-NAME-treated rats but not in rats that were treated with L-NAME + sildenafil. CONCLUSION: The sildenafil-induced attenuation of the deleterious hemodynamic and cardiac morphological effects of L-NAME in cardiac myocytes is mediated (at least in part) by the inhibition of phosphodiesterase-5.

Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles

OBJECTIVES: We investigated the influence of sildenafil on cardiac contractility and diastolic relaxation and examined the distribution of phosphodiesterase-5 in the hearts of hypertensive rats that were treated with by NG-nitro-L-arginine methyl ester (L-NAME). METHODS: Male Wistar rats were treated with L-NAME and/or sildenafil for eight weeks. The Langendorff method was used to examine the effects of sildenafil on cardiac contractility and diastolic relaxation. The presence and location of phosphodiesterase-5 and phosphodiesterase-3 were assessed by immunohistochemistry, and cGMP plasma levels were measured by ELISA. RESULTS: In isolated hearts, sildenafil prevented the reduction of diastolic relaxation (dP/dt) that was induced by L-NAME. In addition, phosphodiesterase-5 immunoreactivity was localized in the intercalated discs between the myocardial cells. The staining intensity was reduced by L-NAME, and sildenafil treatment abolished this reduction. Consistent with these results, the plasma levels of cGMP were decreased in the L-NAME-treated rats but not in rats that were treated with L-NAME + sildenafil. CONCLUSION: The sildenafil-induced attenuation of the deleterious hemodynamic and cardiac morphological effects of L-NAME in cardiac myocytes is mediated (at least in part) by the inhibition of phosphodiesterase-5.

[Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs].

BACKGROUND: Arginine vasopressin (AVP) has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8) and AVP (n=8) groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0 U/kg/min), at them 20-min intervals. Heart rate (HR) and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01 U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0 U/kg/min) a progressive increase in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were observed, with a significant decrease in HR and the cardiac index (CI). A significant increase in the pulmonary vascular resistance index (PVRI) was also observed with the 1.0 U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0 U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed.

Infusão intravenosa de vasopressina causa efeitos cardiovasculares adversos dose-dependentes em cães anestesiados / Infusión intravenosa de vasopresina causa efectos cardiovasculares adversos dependientes de la dosis en canes anestesiados / Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs

FUNDAMENTO: A arginina-vasopressina (AVP) tem sido amplamente utilizada no tratamento do choque vasodilatador. Entretanto, há muitas questões relativas ao seu uso clínico, especialmente em altas doses, pois sua utilização pode estar associada a efeitos cardíacos adversos. OBJETIVO: Investigar os efeitos cardiovasculares da AVP em infusão IV contínua nos parâmetros hemodinâmicos em cães. MÉTODOS: Dezesseis cães saudáveis sem raça definida, anestesiados com pentobarbital, receberam um cateter intravascular e foram aleatoriamente designados para dois grupos: controle (solução salina - placebo; n=8) e AVP (n=8). O grupo do estudo recebeu infusão de AVP por três períodos consecutivos de 10 minutos a doses logaritmicamente progressivas (0,01; 0,1 e 1,0 U/kg/min), a intervalos de 20 minutos. A frequência cardíaca (HR) e as pressões intravasculares foram continuamente registradas. O debito cardíaco foi medido através do método de termodiluição. RESULTADOS: Nenhum efeito hemodinâmico significante foi observado durante a infusão de 0,01 U/kg/min de AVP, mas com as doses mais altas, de 0,1 e 1,0U/kg/min, houve um aumento progressivo na pressão arterial média (PAM) e índice de resistência vascular sistêmica (IRVS), com significante diminuição na frequência cardíaca (FC) e índice cardíaco (IC). Com a dose de 1,0 U/kg/min, também foi observado um aumento significante no índice de resistência vascular pulmonar (IRVP), principalmente devido à diminuição no IC. CONCLUSÃO: A AVP em doses entre 0,1 e 1,0 U/kg/min resultou em significantes aumentos na PAM e no IRVS, com efeitos inotrópicos e cronotrópicos negativos em animais saudáveis. Embora essas doses sejam de 10 a 1.000 vezes maiores do que as rotineiramente utilizadas no tratamento do choque vasodilatador, nossos dados confirmam que a AVP deveria ser usada cuidadosamente e sob rígida monitoração hemodinâmica na prática clínica, especialmente se doses maiores do que 0,01 U/kg/min forem necessárias.

BACKGROUND: Arginine vasopressin (AVP) has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8) and AVP (n=8) groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0U/kg/min), at them 20-min intervals. Heart rate (HR) and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0U/kg/min) a progressive increase in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were observed, with a significant decrease in HR and the cardiac index (CI). A significant increase in the pulmonary vascular resistance index (PVRI) was also observed with the 1.0U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed.

FUNDAMENTO: La arginina-vasopresina (AVP) ha sido ampliamente utilizada en el tratamiento del choque vasodilatador. No obstante, hay muchos aspectos relativos a su uso clínico, especialmente en altas dosis, pues su utilización puede estar asociada a efectos cardíacos adversos. OBJETIVO: Investigar los efectos cardiovasculares de la AVP en infusión IV continua en los parámetros hemodinámicos en canes. MÉTODOS: Dieciséis canes saludables sin raza definida, anestesiados con pentobarbital, recibieron un catéter intravascular y fueron aleatoriamente designados para dos grupos: control (solución salina - placebo; n=8) y AVP (n=8). El grupo del estudio recibió infusión de AVP por tres períodos consecutivos de 10 minutos a dosis logarítimicamente progresivas (0,01; 0,1 y 1,0 U/kg/min), a intervalos de 20 minutos La frecuencia cardíaca (HR) y las presiones intravasculares fueron registradas continuamente. El débito cardíaco fue medido a través del método de termodilución. RESULTADOS: No se observó ningún efecto hemodinámico significativo durante la infusión de 0,01 U/kg/min de AVP, pero con las dosis más altas, de 0,1 y 1,0 U/kg/min, hubo un aumento progresivo en la presión arterial media (PAM) y en el índice de resistencia vascular sistémica (IRVS), con significativa disminución en la frecuencia cardíaca (FC) e índice cardíaco (IC). Con la dosis 1,0 U/kg/min, también se observó un aumento significativo en el índice de resistencia vascular pulmonar (IRVP), principalmente debido a la disminución en el IC. CONCLUSIÓN: La AVP en dosis entre 0,1 y 1,0 U/kg/min resultó en significativos aumentos en la PAM y en el IRVS, con efectos inotrópicos y cronotrópicos negativos en animales saludables. Aunque estas dosis sean de 10 a 1.000 veces mayores que las rutinariamente utilizadas en el tratamiento del choque vasodilatador, nuestros datos confirman que la AVP debería ser usada cuidadosamente y bajo rígido monitoreo hemodinámico en la práctica clínica, especialmente ...

[Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs.] / Infusão intravenosa de vasopressina causa efeitos cardiovasculares adversos dose-dependentes em cães anestesiados.

BACKGROUND: Arginine vasopressin (AVP) has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8) and AVP (n=8) groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0U/kg/min), at them 20-min intervals. Heart rate (HR) and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0U/kg/min) a progressive increase in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were observed, with a significant decrease in HR and the cardiac index (CI). A significant increase in the pulmonary vascular resistance index (PVRI) was also observed with the 1.0U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed. Martins, LC et al.

Acute effects of pharmacotherapies in blood pressure in normotensive moderate smokers.

This study was designed to evaluate the changes in arterial blood pressure (BP) and heart rate (HR) in moderate smokers during smoking abstinence after 7 days of treatment with bupropion alone, transdermal nicotine or bupropion combined with transdermal nicotine. Twenty-four healthy moderate smokers (12 female/12 male; 40+/-7 years) were evaluated randomly on five occasions and their systolic, diastolic, mean arterial blood pressure (MAP) and HR were measured by a Finapres device for 10 h, immediately after smoking interruption. All of the 24 smokers participated on five protocols during 7 days: control group (C) - no drugs; placebo group (PL); bupropion group (BUP) 150-300 mg; transdermal nicotine group (TN) - 21 mg; and BUP+TN-nicotine patch. Concomitantly, the subjects were evaluated by ABPM (ambulatory BP monitoring). All of BP parameters monitored shown significant statistical differences in the BUP, TN and BUP+TN groups compared with the controls (p<0.05), when measured by Finapres. The HR remained unaltered in all of the groups. No significant differences were seen in the BP or HR during the 24-h ABPM. These findings indicate that in moderate smokers, bupropion, transdermal nicotine or bupropion associated with transdermal nicotine caused an elevation in the BP after acute smoking interruption.

Aldosterone escape with diuretic or angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy in patients with mild to moderate hypertension.

Renin-angiotensin-aldosterone system (RAAS) hyperactivity is implicated in the development of hypertension and progressive damage in target organs. Chronic inhibition of the RAAS or use of thiazide-type diuretics may trigger an aldoster-one escape. The aim of this study was to assess this phenomenon in hypertensive patients treated with thiazide-type diuretics (hydrochlorothiazide [HCTZ]) or single or double blockade of the RAAS (irbesartan [IRBE], quinapril [QUIN], and IRBE+QUIN). Blood pressure levels were obtained by 24-hour ambulatory blood pressure monitoring. Plasma renin activity and aldosterone levels were determined by immunoradiometric assay. Blood pressure level was normalized in the 4 treatment groups; the HCTZ and IRBE+QUIN groups showed an increased plasma aldosterone level after 12 weeks (9.1+/-2.2 to 14.1+/-1.4 and 6.9+/-1.9 to 12.9+/-2.3 ng/dL, respectively; P<.05), whereas plasma renin activity was increased only in the HCTZ group (0.9+/-0.2-1.7+/-0.2 ng/mL/h; P<.05). The increase in plasma aldosterone level after 12 weeks of HCTZ and IRBE+QUIN therapy suggests early aldosterone escape.

Hemodynamic effects of a combination of bupropion and nicotine in anesthetized dogs.

Bupropion has been used to treat psychic depression and as a therapy for smoking cessation, the latter mainly in association with nicotine. However, there have been no detailed studies of the hemodynamic effects of the association of bupropion with nicotine during replacement therapy. In this study, we evaluated the effects of such an association on the cardiovascular parameters in anesthetized dogs. Bupropion, either alone or together with nicotine, had no significant effect on the cardiac index (CI; 4.7 +/- 0.2 vs 4.3 +/- 0.1 and 3.5 +/- 0.3 vs 3.4 +/- 0.3 L x min(-1) x m(2), respectively; mean +/- SEM) and mean arterial pressure (MAP; 134 +/- 5.0 vs 145 +/- 11.0 and 118 +/- 5.0 vs 133 +/- 10.5 mmHg, respectively). There was a slight but significant increase in the systemic vascular resistance index (SVRI; 2,165 +/- 93 vs 2,645 +/- 126 and 2,335 +/- 100 vs 2,737 +/- 200 dyn x cm(-5)m(-2), respectively). However, there was a significant increase in the mean pulmonary artery pressure (MPAP; 20 +/- 0.8 vs 25 +/- 1.6 and 18 +/- 1.3 vs 25 +/- 1.6 mmHg, respectively; p < 0.05) and pulmonary vascular resistance index (IRVP; 194 +/- 11 vs 272 +/- 21 and 206 +/- 32 vs 307 +/- 42 dyn x cm-5m(-2), respectively; p < 0.05). These results show that bupropion alone or in association with nicotine does not markedly affect most hemodynamic parameters of the systemic circulation, although the significant increase in MPAP and IRVP can elevate the pulmonary pressure.

Sildenafil reduces cardiovascular remodeling associated with hypertensive cardiomyopathy in NOS inhibitor-treated rats.

Many of the physiological responses to nitric oxide (NO) are mediated by cyclic 5'-guanosine monophosphate (cGMP), the intracellular levels of which are regulated by phosphodiesterase type 5 (PDE5). In situations of reduced NO formation, the inhibition of PDE5 by selective inhibitors such as sildenafil could be beneficial in restoring physiological functions by enhancing the intracellular levels of cGMP. In this study, we evaluated the effects of sildenafil on the hemodynamic and histological alterations induced by the chronic treatment of rats with N(omega)-nitro-L-arginine-methyl ester (L-NAME). After 8 weeks of concomitant treatment with sildenafil and L-NAME, arterial blood pressure was significantly lower (P<0.05) than in L-NAME-treated rats. The fall in blood pressure was associated with a slight reduction in the total peripheral vascular resistance (P<0.05). Sildenafil partially prevented the decrease in cardiac output seen in L-NAME-treated rats. Morphologically, sildenafil reduced the total area of the myocardial lesions and attenuated the cardiomyocyte and vascular smooth muscle remodeling seen with L-NAME. These results show that sildenafil prevented the deleterious hemodynamic and morphological alterations associated with L-NAME-induced hypertension. This beneficial effect was probably mediated by an increase in cardiac and vascular cGMP levels as reflected in circulating plasma cGMP levels.

Blood pressure circadian rhythm and endothelial function in heavy smokers: acute effects of transdermal nicotine.

Nicotine replacement therapy appears to be safe when used by healthy patients to aid in smoking cessation; however, the immediate acute effects of nicotine replacement therapy on the circadian rhythm of blood pressure (BP) and endothelial function in heavy smokers are not well understood. Twenty-six heavy smokers were requested to stop smoking for 48 hours. BP and heart rate were recorded over 48 hours by ambulatory BP monitoring, with beat-to-beat changes being monitored for the first 10 hours by a noninvasive finger device. The reactivity of the brachial artery was evaluated using flow-mediated dilation immediately after smoking cessation, before the application of a 21-mg nicotine patch or placebo patch, and 24 hours after patch placement. Transdermal nicotine caused a mild but significant elevation in BP in the early morning in 21 of 26 volunteers. The decrease in nocturnal BP was attenuated in patients with the nicotine patch compared with the placebo patch; this was associated with impaired endothelium-dependent vasodilation.

Low-renin (volume dependent) mild-hypertensive patients have impaired flow-mediated and glyceryl-trinitrate stimulated vascular reactivity.

BACKGROUND: Low-renin (volume-dependent) hypertension represents 25-30% of all cases of primary hypertension. Endothelial dysfunction and vascular remodeling are associated with hypertension but their relevance to volume-dependent hypertension (VDH) is not yet known. To evaluate this, flow-mediated dilation (FMD) of the brachial artery and the carotid intima-media thickness in the distal common carotid artery were measured and compared between renin-dependent mild-hypertensive patients (RDH) and controls. METHOD AND RESULTS: The study group comprised 40 mild-hypertensive patients and 25 controls. Plasma renin activity (PRA), plasma aldosterone concentration, angiotensin II and nitrite/nitrate plasma levels were measured. According to PRA, subjects were classified as VDH (<0.6 ng . ml (-1) . h(-1)), or RDH (>0.6 ng . ml(-1) . h (-1)). Vascular function was evaluated by FMD before and after reactive hyperemia (RH) and glyceryl-trinitrate (GTN) administration. FMD in response to RH and GTN in the VDH group when compared with RDH group was 10.2+/-2.8% vs 13.3+/-3.6% (p=0.01); and 16.0+/-3.5% vs 19.9+/-4.5% (p=0.01), respectively. CONCLUSION: This study showed impaired FMD and reduced GTN response in mildly hypertensive patients with low-renin plasma levels.