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

Abstract

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.

• Authors: Johannes Wild, Rebecca Schüler, Tanja Knopp, Michael Molitor, Sabine Kossmann, Thomas Münzel, Andreas Daiber, Ari Waisman, Philip Wenzel, Susanne Helena Karbach
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 17 (Aug 30 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31480330 (Publication Type: Journal Article)

Chemical References

• Telmisartan

Topics

• Animals
• Blood Pressure (drug effects)
• Endothelium, Vascular (drug effects, pathology, physiopathology)
• Inflammation (pathology)
• Mice
• Oxidative Stress (drug effects)
• Psoriasis (drug therapy, physiopathology)
• Skin (drug effects, pathology)
• Telmisartan (pharmacology, therapeutic use)