RESUMEN
Shear stress stimulates nitric oxide (NO) release in endothelial cells. Stretch-activated ion channels (SACs) and the transient receptor potential vanilloid type 1 (TRPV1) receptor respond to mechanical stimulus and are permeable to Na(+), Ca(2+) and K(+). The influence of SACs and the TRPV1 receptor on NO release on the heart and on the vascular reactivity of the thoracic aorta (TA) was studied. Experiments were performed in isolated perfused heart, cultured endothelial cells and TA rings from Wistar rats. Capsaicin (10 µM, 30 µM) was used as a NO release stimulator, capsazepine (6 µM, 10 µM) was used as a capsaicin antagonist and gadolinium (3 µM, 5 µM) was used as an inhibitor of SACs. NO was measured by the Kelm and Tenorio methods. Left ventricular pressure was recorded and coronary vascular resistance was calculated. Capsaicin increased NO release in the heart by 58% (395±8 pmol/mL to 627±23 pmol/mL). Capsazepine and gadolinium inhibited NO release by 74% and 82%, respectively. This tendency was similar in all experimental models. Capsaicin attenuated the effects of norepinephrine (10 M to 7 M) on TA and had no effect in the presence of N (ω)-nitro-L-arginine methyl ester. Therefore, the authors conclude that SACs and the TRPV1 receptor are both present in the coronary endothelium and that both participate in Ca(2+)-dependent NO release.
RESUMEN
The convenience to count with a safe and effective pharmacological wealth for atrial fibrillation treatment had conduced, in a way, to a deep depuration of the vast array of antiarrhythmic drugs, keeping only a very restricted number of compounds with a widely proved anti-atrial activity. On the other hand, it had lead to the discovery of the pathophysiological concepts that point to novel therapeutic targets. Within these objectives is that new antiarrhythmic drugs with preferential, even selective, activity on myocardial atrium ion channels had been developed. Among these new antiarrhythmics, dofetilide, and AVE0118, are taken into account. In addition, new possibilities are opened based on the knowledge of the cardioprotective-antiarrhythmic qualities of the opioidergic system.
Asunto(s)
Antiarrítmicos/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Compuestos de Bifenilo/uso terapéutico , Fenetilaminas/uso terapéutico , Bloqueadores de los Canales de Potasio/uso terapéutico , Sulfonamidas/uso terapéutico , Administración Oral , Antiarrítmicos/administración & dosificación , Antiarrítmicos/efectos adversos , Antiarrítmicos/farmacología , Fibrilación Atrial/fisiopatología , Compuestos de Bifenilo/administración & dosificación , Compuestos de Bifenilo/farmacología , Electrofisiología , Atrios Cardíacos/efectos de los fármacos , Humanos , Canales Iónicos/efectos de los fármacos , Fenetilaminas/administración & dosificación , Fenetilaminas/farmacología , Bloqueadores de los Canales de Potasio/administración & dosificación , Bloqueadores de los Canales de Potasio/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores Opioides/efectos de los fármacos , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacología , Factores de TiempoRESUMEN
AIMS: Hypertension remains as a major cause of cardiovascular morbidity in MÚxico. The Health National Survey 2000 of MÚxico was performed to analyze the current status of the prevalence of some risk factors such as diabetes, hypertension (HTA), obesity, smoking, and proteinuria. METHODS: A National Survey was carried out in MÚxico where 45,300 individuals between 20 to 69-y.o. were screened. The estimated sample size was calculated considering the total number of persons into the mentioned age; a minimal prevalence of 6 of the included risk factors, at a significance level of 0.05; a maximum relative error of 0.145, and a rate of response of at least 70. Diagnosis of HTA was accepted in: previous medical diagnosis with prescription of antihypertensive drugs, or high blood pressure (> or = 140/90 mmHg) detected during the interview. Data were adjusted for the national distribution of age-groups and gender (established in 2000, INEGI). RESULTS: 38,377 (98.8) individuals were correctly screened for blood pressure. The prevalence of hypertension in MÚxico was 30.05 (34.2 in men and 26.3 in women). The prevalence was directly related with age and gender. The percentage of mexicans with HTA after 50-y.o. is > 50. The prevalence was greater in women after 50-y.o. Among persons with hypertension, treatment was detected in 46 and approximately 20 of them were controlled (< 140/90 mmHg). The percentage of mexicans with HTA who were unaware that they have high blood pressure was 61. The total percentage of HTA controlled was 14.6. The North states had the greater prevalence (approximately 34) of HTA while South states had the lower prevalence (27). The odds ratio (age/sex-adjusted) for HTA were: for diabetes 1.54(CI95, 1.44-1.63); for obesity 2.3 (CI 95, 2.22-2.43); for smoking 1.26 (CI 95, 1.21-1.32). For proteinuria subjects, 40 had HTA. CONCLUSIONS: Around 15 millions of mexicans between 20 to 69-y.o. had hypertension, 60 of them are unaware. The prevalence of hypertension in MÚxico (30.05) has increased. Among persons with hypertension -15 are controlled. The North of MÚxico has the higher prevalence of hypertension. Diabetes, smoking, and obesity increase the risk of hypertension. The 2000 National Survey of Health shows the epidemiological trend in several important chronic diseases in MÚxico and declare an urgent need of new strategies for detection, control and treatment of hypertension.