Evaluation of cardiovascular parameters of a selenium-based antihypertensive using pulsed Doppler ultrasound.
The pharmacology of selenium is of much interest because selenium deficiency has been linked to cardiovascular diseases, cancer, and arthritis, and selenoenzymes are critical cellular antioxidants. We have previously reported that phenyl-2-aminoethylselenide (PAESe) and its derivatives represent a novel class of selenium-based antihypertensive agents that exhibit unique biochemical and pharmacologic properties. We now report on experiments designed to probe the hemodynamic mechanism of action of these compounds in spontaneously hypertensive rats (SHR). A noninvasive pulsed Doppler ultrasound probe was used to measure peak blood flow velocity in the aortic arch from the right second intercostal space. PAESe was found to increase peak aortic blood flow velocity (+44%), heart rate (+16%), and blood flow acceleration (+105%), while decreasing left ventricular ejection time (LVET) (-37%) concomitant 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 in LVET (+42%) and a decrease in heart rate (-18%). Taken together, our results suggest that PAESe decreases blood pressure via a decrease in peripheral resistance, which overcomes the initial increase in heart rate and acceleration to give a net decrease in MAP.
Overcast
J D
JD
School of Chemistry and Biochemistry and School of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Ensley
A E
AE
Buccafusco
C J
CJ
Cundy
C
C
Broadnax
R A
RA
He
S
S
Yoganathan
A P
AP
Pollock
S H
SH
Hartley
C J
CJ
May
S W
SW
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D004334:Drug Administration Schedule; D005021:Ethylamines / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D018617:Ultrasonography, Doppler, Pulsed
D000959:Antihypertensive Agents; D005021:Ethylamines; D016566:Organoselenium Compounds; D006830:Hydralazine; C056035:phenyl-2-aminoethylselenide