Sustained antihypertensive effect of chronic oral administration of 6-iodo-amiloride, a sodium channel blocker, in spontaneously hypertensive rats.
We have previously shown that a 10-min intravenous infusion of 6-iodo-amiloride, an analogue of the sodium channel blocker amiloride, causes a sustained decrease in blood pressure in two genetic models of hypertension, spontaneously hypertensive rats (SHR) and Dahl salt-sensitive (DS) rats. In contrast, the same infusion produced only a transient decrease in blood pressure in two renal models of hypertension, viz. one-kidney, one clip, and reduced renal mass-saline rats. With these findings, we suggested that 6-iodo-amiloride has potential both as a diagnostic probe and as a therapeutic agent in genetic models of hypertension. The aim of the present study was to examine the effectiveness of 6-iodo-amiloride as a long-term antihypertensive agent and determine the mechanism of its antihypertensive action. We administered 6-iodo-amiloride to SHR for 4 weeks in the drinking fluid (tap water). The treatment with 6-iodo-amiloride caused a significant decrease in blood pressure but had no effect on urine volume or urinary excretion of sodium and potassium. These data strongly suggest that 6-iodo-amiloride is an effective long-term antihypertensive agent in genetic types of hypertension.
Pamnani
M B
MB
Department of Physiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Bryant
H J
HJ
Whitehorn
W V
WV
Cragoe
E J
EJ
Haddy
F J
FJ
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D015222:Sodium Channels / Q000187:drug effects*
D000959:Antihypertensive Agents; D015222:Sodium Channels; C029230:6-iodoamiloride; D000584:Amiloride