Inflammatory reaction versus endogenous peroxisome proliferator-activated receptors expression, re-exploring secondary organ complications of spontaneously hypertensive rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are involved in the pathological changes of hypertension. Three peroxisome proliferator-activated receptors (PPARs) have been identified: PPARalpha, PPARbeta/delta, and PPARgamma, all of which have multiple biological effects, especially the inhibition of inflammation. The aim of this study was to evaluate PPAR isoforms expression profile in important organs of spontaneously hypertensive rats (SHR) and to understand the modulation of endogenous PPAR isoforms under inflammatory condition.</p><p><b>METHODS</b>Tissues (kidney, liver, heart, and brain) were dissected from SHR and age-matched control Wistar-Kyoto rats (WKY) to investigate the abundance of PPAR isoforms and PPAR-responsive genes (acyl-CoA oxidase and CD36). The expression of CCAAT/enhancer-binding protein delta (C/EBPdelta), which can trans-activate PPARgamma expression, was also observed. The inflammatory response was analyzed by the expression of inflammatory mediators inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, interleukin-1 beta (IL-1beta), and tumor necrosis factor alpha (TNFalpha), and formation of carbonyl and nitrated proteins.</p><p><b>RESULTS</b>The expressions of 3 PPAR isoforms and PPAR-responsive genes were markedly upregulated in SHR compared with those of WKY. Specifically, the expression of PPARalpha protein in the kidney, liver, heart and brain increased by 130.76%, 91.48%, 306.24%, and 90.70%; PPARbeta/delta upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPARgamma increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPARgamma, the expression of C/EBPdelta was also dramatically elevated in SHR. Inflammatory mediators expressions were significantly increased in the most organs of SHR than WKY. As a consequence, increased formation of carbonyl and nitrated proteins were also observed in the most organs of SHR.</p><p><b>CONCLUSIONS</b>These findings suggest an enhanced inflammatory response in the organs of SHR, which might play a key role in pathogenesis of hypertension and secondary organ complications. Changes (increases) in PPARs expression may reflect a compensatory mechanism to the inflammatory status of hypertensive rats.</p>

Inflammation of different tissues in spontaneously hypertensive rats / 生理学报

The hypertension is one of chronic vascular diseases, which often implicates multiple tissues causing stroke, cardiac hypertrophy, and renal failure. A growing body of evidence suggests that inflammatory mechanisms are important participants in the pathophysiology of hypertension. In this study, the inflammatory status of these tissues (kidney, liver, heart, and brain) in spontaneously hypertensive rats (SHR) was analyzed and its molecular mechanism was explored. The tissues were dissected from SHR and age-matched control Wistar-Kyoto (WKY) rats to investigate the abundance of inflammation-related mediators (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma). mRNA levels were determined by reverse transcription-polymerase chain reaction and protein expression was evaluated by Western blot. To evaluate the oxidative stress of tissues, carbonyl protein content and total antioxidant capacity of tissues were detected by spectrophotometry and ferric reduction ability power (FRAP) method. The results suggest that: (1) Expressions of inflammation-related mediators (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma) in SHR were higher compared with those in WKY rats except no evident increase of IL-1beta mRNA in liver and brain in SHR. (2) Tissues in SHR contained obviously increased carbonyl protein (nmol/mg protein) compared to that in WKY rats (8.93+/-1.08 vs 2.27+/-0.43 for kidney, 2.23+/-0.23 vs 0.17+/-0.02 for heart, 13.42+/-1.10 vs 5.72+/-1.01 for brain, respectively, P<0.05). However, no evident difference in the amount of carbonyl protein in liver was detected between SHR and WKY rats. (3) Total antioxidant capacities of kidney, liver, heart and brain were markedly lower in SHR than that in WKY rats (P<0.05). Thus, the present data reveal a higher inflammatory status in the important tissues in SHR and indicate that inflammation might play a potential role in pathogenesis of hypertension and secondary organ complications.