Keratinocyte-specific angiotensin II receptor-associated protein deficiency exacerbates angiotensin II-dependent hypertension via activation of the skin renin-angiotensin system.

ABSTRACT: The skin has recently been highlighted as a new player regulating blood pressure (BP). Here we show the role of skin renin-angiotensin system (RAS) in hypertension. In human subjects, skin expression of angiotensin II (Ang II) type 1 receptor (AT1R)-associated protein (ATRAP), which inhibits pathological AT1R signaling, is inversely correlated with systolic BP. Keratinocyte-specific ATRAP knockout male mice (KO) exhibit exacerbated Ang II-induced hypertension and skin-specific increases in angiotensinogen and Ang II levels. In keratinocyte-specific ATRAP and AT1R knockout male mice, Ang II-induced skin angiotensinogen excess and exaggerated hypertension seen in KO are eliminated. Although body fluid volume is comparable between the genotypes, the urine volume per water intake in Ang II-inf

SUBMITTER: Taguchi S 

PROVIDER: S-EPMC12123019 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature