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Vardenafil is effective and well tolerated in patients with PAH at a dose of 5 mg twice daily.

Hormone-sensitive lipase (HSL) is rate-limiting for diacylglycerol and cholesteryl ester hydrolysis in adipose tissue and essential for complete hormone-stimulated lipolysis. Gene expression profiling in HSL−/− mice suggests that HSL is important for modulating adipogenesis and adipose metabolism. To test whether HSL is required for the supply of intrinsic ligands for PPARγ for normal adipose differentiation, HSL−/− and wild type (WT) littermates were fed normal chow (NC) and high fat (HF) diets supplemented with or without rosiglitazone (200 mg/kg) for 16 weeks. Results show that supplementing rosiglitazone to a NC diet completely normalized the decreased body weight and adipose depots in HSL−/− mice. Additionally, rosiglitazone resulted in similar serum glucose, total cholesterol, FFA and adiponectin values in WT and HSL−/− mice. Furthermore, rosiglitazone normalized the expression of genes involved in adipocyte differentiation, markers of adipocyte differentiation, and enzymes involved in triacylglycerol synthesis and metabolism, and cholesteryl ester homeostasis, in HSL−/− mice. Supplementing rosiglitazone to a HF diet resulted in improved glucose tolerance in both WT and HSL−/− animals and also partial normalization in HSL−/− mice of abnormal WAT gene expression, serum chemistries, organ and body weight changes. In vitro studies showed that adipocytes from WT animals can provide ligands for activation of PPARγ, and that activation is further boosted following lipolytic stimulation; whereas adipocytes from HSL−/− mice displayed attenuated activation of PPARγ, with no change following lipolytic stimulation. These results suggest that one of the mechanisms by which HSL modulates adipose metabolism is by providing intrinsic ligands or pro-ligands for PPARγ.