The effect of intermittent administration of sustained release isosorbide dinitrate (sr-ISDN) in rats with volume overload heart.
Recently, it has been reported that intermittent administration of nitrate, with a nitrate-free interval of 10 to 12 hr eliminated expression of tolerance, and maintained its hypotensive effect. In the present study, we evaluated whether nitrate tolerance developed or not with an intermittent administration of sr-ISDN (5 mg/kg/ once a day) in Wistar rats. The effect of this administration protocol for sr-ISDN on the volume overload heart model, aortovenous fistula, was also examined. Furthermore, blood pressure was monitored by radio telemetry during sr-ISDN (5 mg/kg/once a day) administration. Nitrate tolerance did not develop, and eccentric hypertrophy due to volume overload was moderated by sr-ISDN administration. Sr-ISDN administration maintained blood pressure lower level than the placebo group. In conclusion, prolonged intermittent administration of sr-ISDN maintained its hypotensive effect during the entire experiment period, without developing tolerance, and moderated efferent hypertrophy with attenuated volume overload.
Shimamura
Shunsuke
S
Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
Ohsawa
Tomoko
T
Kobayashi
Masayuki
M
Hirao
Hidehiro
H
Shimizu
Miki
M
Tanaka
Ryou
R
Yamane
Yoshihisa
Y
D000704:Analysis of Variance; D000818:Animals; D001164:Arteriovenous Fistula / Q000150:complications / Q000188:drug therapy*; D001794:Blood Pressure; D002312:Cardiomyopathy, Hypertrophic / Q000188:drug therapy / Q000209:etiology; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004351:Drug Resistance / Q000502:physiology*; D004452:Echocardiography; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013686:Telemetry; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate