The Role of Intracellular Renin in Central Cardiovascular Regulation and Fluid Homeostasis
Hypertension is one of the most common diseases in the world. Patients with high blood pressure suffer an increased risk of developing type II diabetes, cardiovascular disease (CVD), renal failure and stroke. The renin-angiotensin system (RAS) has been identified to play a pivotal role in blood pressure regulation. As shown in the following figure, the final pressor of RAS is angiotensin II (Ang-II), which is the product of enzymatic processing of angiotensin I (Ang-I) by angiotensin-converting enzyme (ACE). Ang-I is derived from angiotensinogen (AGT) processed by the aspartyl protease renin. Renin is mainly released from juxtaglomerular (JG) cells at the afferent arterioles of pre-glomerular capillaries in the kidney under the conditions of decreased renal perfusion pressure or the activation of sympathetic nervous system. The physiological effects resulting from Ang-II binding to angiotensin II type 1 receptor (AT1R) include vasoconstriction, sodium reabsorption at proximal tubules, aldosterone release and increased water intake.
While systemic circulating RAS has had widespread acceptance for its role in hypertension since 1898, some new concepts such as tissue specific RAS including a RAS inside the Blood Brain Barrier (BBB) is beginning to gain more importance as experimental data accumulates. My project focuses on the contribution of a novel intracellular isoform of renin to hypertension and other cardiovascular aspects. This isoform is predominantly expressed in the brain, and is enzymatically active in vivoas has been supported by published data.
