Journal Article

Telmisartan Lowers Elevated Blood Pressure in Psoriatic Mice without Attenuating Vascular Dysfunction and Inflammation

Münzel, Thomas, Wenzel, Philip, Wild, Johannes, Kossmann, Sabine, Karbach, Susanne Helena, Molitor, Michael, Schüler, Rebecca, Daiber, Andreas, Knopp, Tanja, Waisman, Ari

2019

Overview

Background: Psoriasis is hallmarked by vascular dysfunction, arterial hypertension, and an increased risk for cardiovascular diseases. We have shown recently that skin-driven interleukin (IL)-17A expression promotes psoriasis-like disease in mice, and this is associated with vascular inflammation, vascular dysfunction, and hypertension. As an intensive risk-factor reduction is recommended for psoriasis patients, we aimed to elucidate the impact of the angiotensin II receptor type 1 (AT1) antagonist telmisartan in a mouse model of severe psoriasis-like skin disease. Methods and Results: Elevated blood pressure measured by tail-cuff plethysmography in mice with keratinocyte-specific IL-17A overexpression (K14-IL-17Aind/+ mice) was significantly reduced in response to telmisartan. Importantly, vascular dysfunction, as assessed by isometric tension studies of isolated aortic rings, vascular inflammation measured by flow cytometry analysis of CD45+CD11b+ immune cells, as well as the increased peripheral oxidative stress levels assessed by L-012-enhanced chemiluminescence were not attenuated by telmisartan treatment of K14-IL-17Aind/+ mice, nor was the persisting skin inflammation. Conclusion: We provide first evidence for an effective antihypertensive treatment in experimental psoriasis by AT1 blockade, but without any impact on vascular inflammation and dysfunction in our mouse model of severe psoriasis-like skin disease. This suggests that vascular function and inflammation in psoriasis might not be attenuated as long as skin inflammation persists.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Blood pressure / Blood Pressure - drug effects / Cardiovascular disease / Clinical medicine / Comorbidity / Cytokines / Drug dosages / Endothelium, Vascular - drug effects / Endothelium, Vascular - pathology / Endothelium, Vascular - physiopathology / Genotype & phenotype / Hypertension / Inflammation / Inflammation - pathology / Mice / Mortality / Oxidative stress / Oxidative Stress - drug effects / Psoriasis / Psoriasis - drug therapy / Psoriasis - physiopathology / Skin - drug effects / Skin - pathology / Skin diseases / Studies / Telmisartan - pharmacology / Telmisartan - therapeutic use