Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect

Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.

Levantamento sobre o uso de plantas medicinais com a terapêutica anticâncer por pacientes da Unidade Oncológica de Anápolis / Survey on medicinal plants used with anticancer therapy by patients from Anapolis Oncology Unit

Este estudo teve por objetivo conhecer o perfil dos pacientes em tratamento contra o câncer da Unidade Oncológica de Anápolis quanto ao uso de plantas medicinais. Foram entrevistados 59 pacientes (42,12% da população estudada) por meio de questionários avaliativos enfatizando características sócio-demográficas e dados referentes à utilização de plantas medicinais. Evidenciou-se o uso indiscriminado de plantas medicinais entre os pacientes. A maioria dos entrevistados compartilha a opinião errônea de que plantas medicinais não fazem mal. A orientação sobre a forma de utilização das plantas ocorre, principalmente, pela informação de familiares ou amigos, e os profissionais da saúde muitas vezes são ignorados neste processo. Constatou-se que as plantas medicinais são utilizadas para o tratamento de enfermidades de baixa a alta gravidade, como o câncer. Dentre as 14 espécies usadas pelos pacientes com finalidade antineoplásica as mais mencionadas foram as popularmente conhecidas como noni, babosa, graviola e romã. Apesar de alguns estudos relatarem atividade antineoplásica ou quimiopreventiva para algumas espécies vegetais, muitas delas podem ser tóxicas ou apresentar potencial risco quando usadas concomitantemente ao tratamento convencional. Desta forma, observa-se que é preciso mais profissionais especializados para orientação sobre o risco de reações adversas e interações medicamentosas no que se refere ao uso de espécies vegetais e a terapêutica do câncer.

This study aims to survey the profile ofcancer patients in the Oncology Unit of Anápolis in relation to the use of medicinal plants. To evaluate socio-demographic characteristics and to retrieve data about on the use of medicinal plants, a questionnaire was filled by 59 patients, or 42.12% of the population under study. A widespread use of plants was found. Most of patients share the wrong idea that medicinal plants are not harmful. Guidance on the use of medicinal plants is given primarily by relatives and friends, and health professional are often ignored in this process. Among the 14 species used by patients with antineoplastic purpose, the most mentioned were popularly species known as "noni", "aloe", "soursop" and "pomegranate". Although some studies have reported chemopreventive or antineoplastic activity for some plant species, many may be toxic or show potential risk when used concurrently with conventional treatment. Thus, we can observe that there is a need for more specialized professionals for the guidance on the risk of adverse reactions and drug interactions in relation to the use of plant species and cancer therapeutics.

Effects of acid-base imbalance on vascular reactivity

Acid-base homeostasis maintains systemic arterial pH within a narrow range. Whereas the normal range of pH for clinical laboratories is 7.35-7.45, in vivo pH is maintained within a much narrower range. In clinical and experimental settings, blood pH can vary in response to respiratory or renal impairment. This altered pH promotes changes in vascular smooth muscle tone with impact on circulation and blood pressure control. Changes in pH can be divided into those occurring in the extracellular space (pHo) and those occurring within the intracellular space (pHi), although, extracellular and intracellular compartments influence each other. Consistent with the multiple events involved in the changes in tone produced by altered pHo, including type of vascular bed, several factors and mechanisms, in addition to hydrogen ion concentration, have been suggested to be involved. The scientific literature has many reports concerning acid-base balance and endothelium function, but these concepts are not clear about acid-base disorders and their relations with the three known mechanisms of endothelium-dependent vascular reactivity: nitric oxide (NO/cGMP-dependent), prostacyclin (PGI2/cAMP-dependent) and hyperpolarization. During the last decades, many studies have been published and have given rise to confronting data on acid-base disorder and endothelial function. Therefore, the main proposal of this review is to provide a critical analysis of the state of art and incentivate researchers to develop more studies about these issues.

Protective effect of N-acetylcysteine against oxygen radical-mediated coronary artery injury

The present study investigated the protective effect of N-acetylcysteine (NAC) against oxygen radical-mediated coronary artery injury. Vascular contraction and relaxation were determined in canine coronary arteries immersed in Kreb's solution (95 percent O2-5 percent CO2), incubated or not with NAC (10 mM), and exposed to free radicals (FR) generated by xanthine oxidase (100 mU/ml) plus xanthine (0.1 mM). Rings not exposed to FR or NAC were used as controls. The arteries were contracted with 2.5 µM prostaglandin F2alpha. Subsequently, concentration-response curves for acetylcholine, calcium ionophore and sodium fluoride were obtained in the presence of 20 µM indomethacin. Concentration-response curves for bradykinin, calcium ionophore, sodium nitroprusside, and pinacidil were obtained in the presence of indomethacin plus Nomega-nitro-L-arginine (0.2 mM). The oxidative stress reduced the vascular contraction of arteries not exposed to NAC (3.93 ± 3.42 g), compared to control (8.56 ± 3.16 g) and to NAC group (9.07 ± 4.0 g). Additionally, in arteries not exposed to NAC the endothelium-dependent nitric oxide (NO)-dependent relaxation promoted by acetylcholine (1 nM to 10 µM) was also reduced (maximal relaxation of 52.1 ± 43.2 percent), compared to control (100 percent) and NAC group (97.0 ± 4.3 percent), as well as the NO/cyclooxygenase-independent receptor-dependent relaxation provoked by bradykinin (1 nM to 10 µM; maximal relaxation of 20.0 ± 21.2 percent), compared to control (100 percent) and NAC group (70.8 ± 20.0 percent). The endothelium-independent relaxation elicited by sodium nitroprusside (1 nM to 1 µM) and pinacidil (1 nM to 10 µM) was not affected. In conclusion, the vascular dysfunction caused by the oxidative stress, expressed as reduction of the endothelium-dependent relaxation and of the vascular smooth muscle contraction, was prevented by NAC.

Ionic radiocontrast inhibits endothelium-dependent vasodilation of the canine renal artery in vitro: possible mechanism of renal failure following contrast medium infusion

To determine if radiocontrast impairs vascular relaxation of the renal artery, segments (4-5 mm in length) of canine renal artery were suspended in vitro in organ chambers to measure isometric force (95 percent O2/5 percent CO2, at 37ºC). Arterial segments with and without endothelium were placed at the optimal point of their length-tension relation and incubated with 10 æM indomethacin to prevent synthesis of endogenous prostanoids. The presence of nonionic radiocontrast (iohexol, Omnipaque 350, 1 ml in 25 ml control solution, 4 percent (v/v)) did not alter endothelium-dependent relaxation to acetylcholine in rings precontracted with both norepinephrine and prostaglandin F2alpha (N = 6). When the rings were precontracted with prostaglandin F2alpha, the presence of ionic contrast did not inhibit the relaxation of the arteries. However, in canine renal arteries contracted with norepinephrine, the presence of ionic radiocontrast (diatrizoate meglumine and diatrizoate sodium, MD-76, 1 ml in 25 ml control solution, 4 percent (v/v)) inhibited relaxation in response to acetylcholine, sodium nitroprusside (N = 6 in each group), and isoproterenol (N = 5; P < 0.05). Rings were relaxed less than 50 percent of norepinephrine contraction. Following removal of the contrast, vascular relaxation in response to the agonists returned to normal. These results indicate that ionic radiocontrast nonspecifically inhibits vasodilation (both cAMP-mediated and cGMP-mediated) of canine renal arteries contracted with norepinephrine. This reversible impairment of vasodilation could inhibit normal renal perfusion and act as a mechanism of renal failure following radiocontrast infusion. In the adopted experimental protocol the isoproterenol-induced relaxation of renal arteries precontracted with norepinephrine was more affected, suggesting a pivotal role of the cAMP system.

Métodos de prevención de las alteraciones estructurales pulmonares en la hernia diafragmática congénita. Estudio experimental con cirugía fetal / Preventive methods of the lung alterations in congenital diaphragmatic hernia. Experimental study with fetal surgery

La hipoplasia pulmonar es la causa de muerte en el 30 al 50 por ciento de los recién nacidos con hernia diafragmática congénita. La ligadura traqueal en el feto, previene esta alteración, estimulando el crecimiento de la vía aérea. El objetivo principal de este trabajo es investigar un método de prevención de la hipoplasia pulmonar, basado en la administración intraamniótica de drogas, pasible de ser utilizado en la especie humana. Fueron operadas 36 conejas en el día 24 de gestación. En el primer grupo de fetos se creó una hernia diafragmática. En otros tres grupos además de la hernia diafragmática se efectuaron tres procedimientos adicionales: a) ligadura traqueal b) administración intraamniótica de dexametasona c) administración intraamniótica de surfactante. Se tomó como grupo control a 14 fetos, no operados, en el día 30, se efectuó una cesarea y se procedió a canular la tráquea de todos los animales para medir los parámetros funcionales (curvas de histéresis y de compliance). Los pulmones fueron recolectados para estudios biométricos: peso, volúmen e histología (evaluación cualitativa) y estudios histomorfométricos: densidad de septos alveolares, número de alvéolos por mm y evaluación de la densidad de fibras elásticas y colágenas. Se observó que la hernia diafragmática provocó una disminución significativa en el peso y volúmen de ambos pulmones, con caída de la histéresis y la complacencia, espesamiento de los septos alveolares, disminución del contenido en fibras elásticas y aumento del colágeno. La administración de surfactante y corticoides intraamnióticos produjeron efectos similares a los de la ligadura traqueal, corrigiendo parcialmente las alteraciones pulmonares en los fetos con hernia diafragmática, presentando el surfactante efectos más acenntuados. Concluímos que la administración intraamniótica de surfactante o dexametasona pueden subsistir a la ligadura traqueal como método experimental de prevención de la hipoplasia pulmonar, presente en los fetos con hernia diafragmática congénita