Proteasome inhibition attenuates angiotensin II‐induced hypertension and vascular remodeling

Abstract

Growing evidence implicates the proteasome in cardiovascular disease. However, its role in hypertension is understudied. Accordingly, this study tested the hypothesis that proteasome inhibition attenuates hypertension development and related vascular remodeling.Male Sprague Dawley rats were given chronic subcutaneous infusion of angiotensin II (AngII) to induce hypertension or vehicle infusion for 2 weeks. The rats were concurrently treated with a proteasome inhibitor, bortezomib (200 μg/kg 3 times per week). Arterial blood pressure was measured from conscious rats via indwelling catheters. After euthanasia the aorta and tibialis anterior skeletal muscle were collected. Histochemical (Masson's Trichrome) and immunohistochemical (CD31) staining were used to estimate wall to lumen ratio and capillary density respectively.Compared to vehicle (131±7 mm Hg), Ang II infusion caused a marked increase in arterial pressure (159±4 mm Hg). Aortic wall to lumen ratio was increased (+20%) whereas capillary density in skeletal muscle was reduced (−30%). Concurrent bortezomib treatment markedly attenuated these responses (arterial pressure 138±5 mm Hg, aorta wall to lumen ratio −1%, capillary density −8%).Collectively, these data suggest that inhibition of the proteasome attenuated Ang II hypertension development and related vascular remodeling. Supported by NIH #2RO1HL63053‐ARRA (DM).