Interactions Between the Immune and the Renin-Angiotensin Systems in Hypertension.

Abstract

The renin–angiotensin system (RAS) is an essential regulator of blood pressure homeostasis. The primary effector molecule of the RAS is angiotensin (Ang) II, an 8-amino acid peptide that initiates tissue-specific processes via binding to the type 1 or 2 angiotensin II receptors (AT1 or AT2). The AT1 receptor is a G-protein–coupled receptor expressed in most tissues throughout the body. Although the rodent expresses 2 AT1 receptor isoforms, AT1A and AT1B, the closest functional homolog to the human AT1 receptor in most rodent tissues is AT1A. The most widely appreciated functions of Ang II signaling via the AT1 receptor are to augment global vascular tone and to promote sodium retention in the kidney, thus playing a crucial role in acute and long-term maintenance of blood pressure.1,2 Ang II elicits these effects by increasing the contractility of vascular smooth muscle, promoting the release of aldosterone from the adrenal cortex, and directly increasing the expression or activity of solute transporters in the renal tubules that promote sodium reabsorption. As such, blockade of the RAS has been a mainstay in the treatment for hypertension and its complications, including cardiovascular and kidney disease.2,3 Although the cause of essential hypertension is unclear, inhibition of the RAS is effective in reducing blood pressure in a wide variety of patients, which suggests that inappropriate RAS activation is common in the pathogenesis of this idiopathic condition. Global RAS inhibitors ameliorate hypertension by blocking the production of Ang II or by preventing activation of the AT1 receptor. These medications are global inhibitors in the sense that they disrupt AT1 receptor signaling concomitantly in all tissues. The ongoing effort to uncover novel pathogenic mechanisms of hypertension has revealed a significant role for …