Beneficial and deleterious effects of rosiglitazone on hypertension development in spontaneously hypertensive rats.
The antihypertensive effect of the peroxisome proliferator-activated receptor (PPAR)gamma agonist rosiglitazone has been reported in patients with diabetes or obesity. The correlation of PPARgamma expression with blood pressure and the therapeutic application of rosiglitazone in spontaneously hypertensive rats (SHR) were investigated in the present study. Systolic blood pressure of 21-week SHR was significantly higher than that of age-matched Wistar-Kyoto rats (WKY) (225 +/- 5 v 144 +/- 2 mm Hg, P <.05). Basal expression levels of PPARgamma proteins in vascular tissues of 21-week SHR were significantly lower than that of age-matched 21-week WKY (P <.05). This reduced expression of PPARgamma was not detected between 5- and 13- week SHR and age-matched WKY. Cardiac PPARgamma expression was also not different among different age groups between SHR and WKY. Chronic treatment with rosiglitazone, but not PPARalpha agonist Wy14643, significantly retarded hypertension development and reversed abnormally faster heart rate in young SHR. An unfavorable effect of rosiglitazone treatment was the increased heart-to-body weight ratio accompanied by left ventricular hypertrophy. In conclusion, vascular PPARgamma protein expression in adult SHR (21 weeks) is significantly decreased in comparison with the age-matched WKY. Chronic rosiglitazone treatment retards hypertension development, but the associated prohypertrophy effect calls for a cautious use of this thiazolidinedindione in the treatment of insulin resistance syndrome associated with hypertension.
Wu
Lingyun
L
Department of Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. liw070@duke.usask.ca
Wang
Rui
R
De Champlain
Jacques
J
Wilson
Thomas W
TW
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000473:pathology; D007668:Kidney / Q000033:anatomy & histology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D047493:PPAR alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D020025:Peroxisome Proliferators / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000077154:Rosiglitazone; D013610:Tachycardia / Q000188:drug therapy; D045162:Thiazolidinediones / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
D000959:Antihypertensive Agents; D047493:PPAR alpha; D047495:PPAR gamma; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C006253:pirinixic acid