| 摘要: | Arsenic is a ubiquitous toxic compound that exists naturally in many sources such as soil, groundwater, and food; in which vast majority forms are Arsenite (As3+) or Arsenate (As5+). Epidemiologic studies documented that arsenic pollution caused black foot disease, cardiovascular diseases (hypertension, hypotension, cardiomyopathy), bladder cancer and skin cancer in many countries in which Taiwan was considered as high arsenic exposure country. However, the effects of arsenic at different concentration on cardiac functions still lack of investigation while some studies mainly focus on inflammatory and cancer mechanisms. In the present study, arsenic was fed orally to Sprague Dawley rats at 1ppm and 3.5ppm in concentration for four weeks and eight weeks duration. Using hemodynamic method as the main tool, the findings suggest that arsenical exposure at low concentration (1ppm) caused hypertension, increase in left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP), alteration in cardiac contractility index after four weeks and even more serve in eight weeks; whereas at the concentration of 3.5ppm, arsenic exposure leaded hypotension (8 weeks), decrease in LVSP and dramatically increase in LVEDP (8 weeks) which is supposed to cause sudden cardiac death. Moreover, QT prolongation, heart rate decline, widen in cardiac cycle length are also induced by arsenic in time-concentration profiles. These alterations are supposed to be the interaction between arsenic and cardiac nerves activity via the changing in calcium homeostasis. Collectively, our quantitative PCR and western blot data strongly suggest that calcium homeostasis may also go through MEF2A, TNNI3, CAMKK2, CALM3 and cardiac hypertrophy relative signaling pathway. |
