Abstract P102: Type I Diabetes Mellitus is More Sensitive to Ang II Due to Increased AT1 Receptor Expression in Afferent Arteriole

Abstract

The prevalence of hypertension is about twice in diabetic subjects than that in non-diabetics. In the presence of hypertension, the progress of diabetic nephropathy has been shown to be more severe and rapid. But the mechanisms for the development of hypertension in diabetes have not been elucidated. We hypothesized that angiotensin II receptor type 1 (AT1 receptor) expression level in renal afferent arteriole is elevated, which enhances the responses to angiotensin II (Ang II) stimulation and contributes to the development of hypertension in diabetes. First, we measured mean arterial pressure (MAP) with telemetry in diabetic and non-diabetic mice with Ang II infusion for 8 weeks. MAP was 26.7 mmHg higher in diabetic mice (157.4±11.3 mmHg) than in non-diabetic mice (130.7±6.4 mmHg). Next, we induced 2-kidney-1-clip Goldblatt hypertension in diabetic mice and non-diabetic mice and measured MAP with telemetry for 8 weeks. MAP was 17.6 mmHg higher in diabetic mice (151.1±9.5 mmHg) than in non-diabetic mice (133.5±4.2 mmHg), indicating blood pressure of diabetic mice is also more responsive to both exogenous and endogenous Ang II than no-diabetic mice. To investigate the mechanisms of the enhanced sensitivity to Ang II, we dissected afferent arterioles from non-diabetic mice and diabetic mice and measured the expression of AT1 receptor mRNA by real-time PCR. AT1 receptor mRNA level was 6 times higher in diabetic mice that in non-diabetic control. AT1 receptor protein abundance in renal cortex was also 5 times higher in diabetic mice than controls. In conclusion, the blood pressure of the diabetic mice are more sensitive to Ang II than non-diabetic controls. Increased AT1 receptor expression in the afferent arterioles may contribute to the development of hypertension in diabetes.