Increased expression of peroxisome proliferator-activated receptor-alpha and -gamma in blood vessels of spontaneously hypertensive rats.

Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated transcription factors that include PPAR-alpha, PPAR-gamma, and PPAR-delta. We hypothesized that PPAR expression in blood vessels could be reduced in hypertension to result in increased vascular growth and reduced apoptosis. We investigated the abundance of PPAR-alpha and PPAR-gamma in aorta and mesenteric arteries from young (6-week-old) and adult (16-week-old) spontaneously hypertensive rats (SHR) compared with age-matched control Wistar-Kyoto rats (WKY). mRNA levels of PPAR-alpha and PPAR-gamma were determined by reverse transcription-polymerase chain reaction. Protein expression was evaluated by Western blot and by immunohistochemistry. PPAR-gamma was expressed in aortic and mesenteric vascular smooth muscle cells (VSMCs) from intact tissue and cultured cells. PPAR-alpha was expressed in intact vascular tissue but was almost undetectable in cultured VSMCs. In mesenteric arteries from adult SHR, PPAR-alpha and PPAR-gamma mRNA levels were significantly greater than in WKY (P<0.05). In aorta, PPAR-alpha mRNA was significantly (P<0.05) more abundant in adult (but not in young) SHR than in WKY, whereas there was no difference in PPAR-gamma mRNA between WKY and SHR. PPAR-alpha and PPAR-gamma mRNA were greater in mesenteric arteries (P<0.05) in young and adult SHR than in WKY. Expression of PPAR-alpha and PPAR-gamma was similar in SHR and WKY in other tissues. In cultured mesenteric VSMCs, PPAR-gamma mRNA was 3-fold higher in SHR than in WKY. Immunohistochemistry demonstrated that PPAR-gamma resided constitutively in the cytoplasm in primary and low-passaged aortic and mesenteric VSMCs, whereas PPAR-alpha was almost undetectable. Thus, aorta and mesenteric resistance arteries from SHR in the prehypertensive and the established phase of hypertension exhibit increased expression of both PPAR isoforms, whereas other tissues do not. Changes (increases) in PPAR expression may play a compensatory role in the remodeling of blood vessels in SHR.