TRPV1 Contributes to Modulate the Nitric Oxide Pathway and Oxidative Stress in the Isolated and Perfused Rat Heart during Ischemia and Reperfusion.

The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here, we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the control of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats perfused according to the Langendorff technique were used to study the effects of an agonist of TRPV1, capsaicin (CS), an antagonist, capsazepine (CZ), and their combination CZ+CS. The hearts were subjected to three conditions: (1) control, (2) ischemia and (3) ischemia-reperfusion. We determined cardiac mechanical activity and the levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue after administration of CS, CZ and CZ+CS. Western blots were used to study the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac mechanical activity and elevating the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.

The Role of the Activation of the TRPV1 Receptor and of Nitric Oxide in Changes in Endothelial and Cardiac Function and Biomarker Levels in Hypertensive Rats.

The purpose of the present study was to analyze the actions of transient receptor potential vanilloid type 1 (TRPV1) agonist capsaicin (CS) and of its antagonist capsazepine (CZ), on cardiac function as well as endothelial biomarkers and some parameters related with nitric oxide (NO) release in L-NG-nitroarginine methyl ester (L-NAME)-induced hypertensive rats. NO has been implicated in the pathophysiology of systemic arterial hypertension (SAHT). We analyzed the levels of nitric oxide (NO), tetrahydrobiopterin (BH4), malondialdehyde (MDA), total antioxidant capacity (TAC), cyclic guanosin monophosphate (cGMP), phosphodiesterase-3 (PDE-3), and the expression of endothelial nitric oxide synthase (eNOS), guanosine triphosphate cyclohydrolase 1 (GTPCH-1), protein kinase B (AKT), and TRPV1 in serum and cardiac tissue of normotensive (118±3 mmHg) and hypertensive (H) rats (165 ± 4 mmHg). Cardiac mechanical performance (CMP) was calculated and NO was quantified in the coronary effluent in the Langendorff isolated heart model. In hypertensive rats capsaicin increased the levels of NO, BH4, cGMP, and TAC, and reduced PDE-3 and MDA. Expressions of eNOS, GTPCH-1, and TRPV1 were increased, while AKT was decreased. Capsazepine diminished these effects. In the hypertensive heart, CMP improved with the CS treatment. In conclusion, the activation of TRPV1 in H rats may be an alternative mechanism for the improvement of cardiac function and systemic levels of biomarkers related to the bioavailability of NO.

[Early arterial reflexion and ventricular extrasystole. A novel mechanism detected with sphygmokinetocardiography]. / Reflexión arterial precoz y extrasistolia ventricular. Un mecanismo novel detectado por esfigmoquinetocardiografía.

UNLABELLED: ANTECEDENT: Through sphygmokynetocardiography (SKCG) an exploratory method that records an electrocardiographic signal, a carotid pulse (CP), and two vibriograms (kinetocardiograms) of the left ventricle (LV) recorded in the left hemithorax (anterior kinetocardiogram, AKC) and the subcostal region of left abdomen (posterior kinetocardiogram of PKC, vibrations transmitted through the hemidiaphragm) we observed a systolic precocious reflection wave (Rw) in the CP and prolongation of LV ejection time (LVET) measured in AKC or in PKC of the previous sinusal pre-extrasystolic beat (PEB) vs control beats (CB) in cases with ventricular extrasystoles (VEs). OBJECTIVE: To demonstrate whether the intervals just mentioned are associated with ventricular extrasystoles. METHOD: Sixty cases: 30 with VEs, group A, and 30 without arrhythmia, group B, were studied through SKCG. The LVET and the arterial reflection index or ARI = Ta-rw/LEVT, Ta-rw = time between initial ventricular impulse to reflexive wave, were measured. RESULTS: Demography was similar in both groups. PEB had a longer LVET than the CB (291 +/- 41 vs 279 +/- 39, p < 0.01) and ARI was shorter (0.36 +/- 0.17 vs 0.58 +/- 0.21, p < 0.001). CONCLUSIONS: 1) Distention of the LV due to Rw, possibly through the well-known experimental mechanism of electromechanic feedback, is believed to underlie the arrhythmia. 2) The observation has important clinical implications.

Desarrollo de un modelo canino de hipertensión ventricular derecha crónica progresiva / DEvelopment of a canine model to produce chronic, progressive right ventricular hypertension

Introducción: En modelos animales se ha producido hipertensión ventricular derecha ocluyendo la arteria pulmonar con bandas hechas de silastic, lino, tygón, o teflón. Estos procedimientos no permiten una oclusión gradual y progresiva que remede lo observado en la condición clínica de hipertensión arterial pulmonar e hipertensión ventricular derecha crónica. El objetivo del presente estudio es crear un modelo donde la obstrucción progresiva sea factible. Material y métodos: Diseñamos tanto un programa de adquisición de datos hemodinámicos como un dispositivo oclusor hidráulico (DOH) del tronco de la arteria pulmonar que permite un control externo de la presión ventricular deseada. Estudiamos durante 6 meses, a 12 perros mestizos sanos de 18 a 28 kg de peso. Realizamos mediciones hemodinámicas cada 2 meses, en condición basal, a 40 mmHg y a 60 mmHg de presión sistólica del ventrículo derecho (PSVD), respectivamente. Resultados: El programa facilitó el análisis instantáneo de múltiples variables hemodinámicas. A 60 mmHg de PSVD, la presión diastólica final del ventrículo derecho incrementó de 4.2 ñ 0.4 mmHg a 13.2 ñ 1.1 mmHg, p < 0.000, el gasto cardiaco ajustado al peso del perro disminuyó de 0.16 ñ 0.03 L/min/kg hasta 0.09 ñ 0.01 L/min/kg, p < 0.000 y la presión diastólica final del ventrículo izquierdo, incrementó de 7.4 ñ 0.8 mmHg a 16.3 ñ 2.8 mmHg, p < 0.000. El dispositivo mantuvo en el tiempo la PSVD requerida. La confiabilidad por coeficiente de correlación intraclase fue de 0.83, P < 0.005. Conclusiones: El modelo de hipertensión ventricular derecha crónica está creado. El programa de captura hemodinámica permite un análisis versátil. El DOH es confiable para mantener la PSVD en el tiempo.

Sistema para la medición no invasiva de la velocidad del pulso arterial en diferentes territorios vasculares / A system for non-invasive measurement of arterial pulse velocity different vascular territories

La velocidad de la onda del pulso arterial (VOP) se ha utilizado como índice de rigidez arterial para valorar algunas patologías cardiovasculares. Aquí se describe el diseño y desarrollo de un sistema para determinar la VOP en las regiones aórto-braqui-húmero-radial (A - m), aórto-ileo-fémoro-pedial (A - p) y aórto-carotidea (A - L), el cual se ensayó en 36 sujetos normotensos (NT) y 34 hipertrofia ventricular izquierda (SHVI). El equipo consta de una computadora a la que se le añadió, bajo diseño específico, un convertidor de analógico, bajo diseño específico, un convertidor de analógico a digital y la electrónica y programación para tomar simultáneamante el electrocardiograma (ECG), dos pulsos fotopletismográficos, una lectura de presión y un pulso oscilométrico. Con estos datos se determinó el intervalo Q-pP (tiempo entre la onda Q de ECG y el pie del pulso periférico) lo que, tomando la distancia entre los sitios de registro y luego de calcular el periodo pre-expulsivo cardiaco, permite determinar la VOP (en metros/segundo) desde la raíz de la aorta al punto distal. Al comparar la VOP en HT vs NT (A - m: 9.3 ñ 2.6 vs. 7.2 ñ 0.8, A - L: 9.5 ñ 2.8 vs. 6.0 ñ 0.9 y A - p: 9.5 ñ 1.8 vs. 7.2 ñ 0.9), la diferencia resultó significativa (p < 0.001) en cada uno de los territorios explorados; lo mismo ocurrió al comparar los casos CHVI contra los SHVI (A - m: 10.5 ñ 1.6 vs. 8.0 ñ 1.9, A - L: 10.2 ñ 1.9 vs 8.0 ñ 1.9 y A - p: 10.5 ñ 2.0 vs. 8.6 ñ 1.2) (p < 0.025). Esto es consistente con la conocida relación mayor presión - mayor rigidez y con lo reportado en otros trabajos que utilizan métodos diferentes para precisar la VOP. El método puede tener aplicación en la clínica