Evaluation of cardiovascular parameters of a selenium-based antihypertensive using pulsed Doppler ultrasound

The pharmacology of selenium is of much interest because selenium deficienc y has been linked to cardiovascular diseases. cancer. and arthritis, and se lenoenzymes are critical cellular antioxidants. We have previously reported that phenyl-2-aminoethylselenide (PAESe) and its derivatives represent a n ovel class of selenium-based antihypertensive agents that exhibit unique bi ochemical and pharmacologic properties. We now report on experiments design ed to probe the hemodynamic mechanism of action of these compounds in spont aneously hypertensive rats (SHR). A noninvasive pulsed Doppler ultrasound p robe was used to measure peak blood flow velocity in the aortic arch from t he right second intercostal space. PAESe was found to increase peak aortic blood now velocity (+44%), heart rate (+16%), and blood flow acceleration ( +105%), while decreasing left ventricular ejection time (LVET) (-37%) conco mitant with a decrease in mean arterial pressure (-54%). These results were compared with the known vasodilator hydralazine. which had similar effects on mean arterial pressure (MAP) and peak velocity but caused an increase i n LVET (+42%) and a decrease in heart rate (-18%). Taken to-ether, our resu lts suggest that PAESe decreases blood pressure via a decrease in periphera l resistance. which overcomes the initial increase in heart rate and accele ration to give a net decrease in MAP.