Abstract: TH-OR76
Activation of the Skin Renin-Angiotensin System Exacerbates Angiotensin II-Induced Hypertension via Skin Vasoconstriction
Session Information
- Hypertension and CVD: Research Advances
October 24, 2024 | Location: Room 5, Convention Center
Abstract Time: 05:00 PM - 05:10 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Taguchi, Shinya, Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
- Azushima, Kengo, Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
- Kitada, Kento, Department of Pharmacology, Faculty of Medicine, Kagawa University, Kida-gun, Kagawa, Japan
- Morisawa, Norihiko, Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore
- Wakui, Hiromichi, Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
- Morita, Ryutaro, Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
- Kawasoe, Kentaro, Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
- Nishiyama, Akira, Department of Pharmacology, Faculty of Medicine, Kagawa University, Kida-gun, Kagawa, Japan
- Tamura, Kouichi, Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
Background
Recent studies suggest skin vasoconstriction and sodium (Na+) accumulation are linked with hypertension. The skin has a localized renin-angiotensin system (RAS), a key regulator of blood pressure (BP), but its functional role remains unclear. This study aims to investigate the role of skin RAS in hypertension.
Methods
Skin tissue from 58 individuals, including hypertensive patients, was used to evaluate the association between skin RAS component expression and office BP. Mice lacking ATRAP (type-1 angiotensin II (Ang II) receptor (AT1R)-associated protein), which selectively inhibits pathological AT1R signaling, in skin keratinocytes (KO: K14Cre;ATRAPflox) were generated. Hypertension was induced by Ang II (500 ng/kg/min) administration.
Results
In the human study, skin expression of ATRAP was inversely correlated with systolic BP (r = −0.41, P < 0.01). Telemetry analysis showed that BP elevation and related cardiac hypertrophy were exacerbated in KO mice compared to controls (mean BP, 123.3 ± 4.7 vs. 132.6 ± 3.1 mmHg, P < 0.05; heart/body weight, 4.7 ± 0.4 vs. 5.2 ± 0.7, P < 0.05). Ang II-infused KO mice had higher skin angiotensinogen levels (P < 0.05), while levels in the kidney and heart were similar in both groups. Ang II levels in the skin were also significantly higher in Ang II-infused KO mice than in controls, whereas plasma Ang II levels were comparable in both groups, suggesting skin-specific enhancement of local RAS activity. AT1R blocker treatment eliminated exaggerated Ang II-induced hypertension and enhancement of skin RAS activity in KO mice. Sympathetic nerve activity, plasma volume, and skin Na+ content did not differ between the groups. In Ang II-infused KO mice, urine volume per water intake increased (P < 0.001), despite similar body weight changes in both groups, suggesting decreased extra-renal water loss. Consistent with these findings, skin blood flow and transepidermal water loss were decreased in Ang II-infused KO mice (P < 0.001 and P < 0.01, respectively). These differences, including exaggerated BP elevation, were eliminated by skin vasodilation via body temperature elevation.
Conclusion
Enhanced skin RAS activity contributes to BP elevation via skin vasoconstriction. Skin RAS may be a novel target for treating hypertension.