| First Author | Taguchi S | Year | 2025 |
| Journal | Nat Commun | Volume | 16 |
| Issue | 1 | Pages | 4789 |
| PubMed ID | 40442063 | Mgi Jnum | J:376066 |
| Mgi Id | MGI:8208881 | Doi | 10.1038/s41467-025-60041-8 |
| Citation | Taguchi S, et al. (2025) Keratinocyte-specific angiotensin II receptor-associated protein deficiency exacerbates angiotensin II-dependent hypertension via activation of the skin renin-angiotensin system. Nat Commun 16(1):4789 |
| abstractText | 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-infused KO is increased, suggesting decreased extra-renal water loss, which is supported by decreased skin blood flow and transepidermal water loss in KO. Body temperature elevation-induced skin vasodilation eliminates these differences, including exaggerated hypertension, indicating the contribution of skin RAS-mediated vasoconstriction to BP elevation. Skin RAS may become a potential strategy for therapeutic interventions in hypertension. |
