Beneficial and deleterious effects of rosiglitazone on hypertension development in spontaneously hypertensive rats

• Published in: American journal of hypertension 2004-09, Vol.17 (9), p.749-756
• Main Authors: Wu, Lingyun, Wang, Rui, de Champlain, Jacques, Wilson, Thomas W.
• Format: Article
• Language: English
• Subjects: Animals; Antihypertensive Agents - pharmacology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; hypertension; Hypertension - drug therapy; Hypertrophy, Left Ventricular - drug therapy; Hypertrophy, Left Ventricular - pathology; Kidney - anatomy & histology; Male; Medical sciences; Myocardium - pathology; Organ Size - drug effects; peroxisome proliferator-activated receptor (PPAR)α; Peroxisome Proliferators - pharmacology; PPAR alpha - antagonists & inhibitors; PPAR alpha - metabolism; PPAR gamma - antagonists & inhibitors; PPAR gamma - metabolism; PPARγ; Pyrimidines - pharmacology; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rosiglitazone; Tachycardia - drug therapy; Thiazolidinediones - pharmacology; ventricular hypertrophy; Weight Gain - drug effects
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/j.amjhyper.2004.04.010

The antihypertensive effect of the peroxisome proliferator-activated receptor (PPAR)γ agonist rosiglitazone has been reported in patients with diabetes or obesity. The correlation of PPARγ 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 PPARγ 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 PPARγ was not detected between 5- and 13- week SHR and age-matched WKY. Cardiac PPARγ expression was also not different among different age groups between SHR and WKY. Chronic treatment with rosiglitazone, but not PPARα 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 PPARγ 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.