Tracing angiotensin II's yin-yang effects on cardiovascular-renal pathophysiology.

Adverse changes in cardiovascular and renal systems are major contributors to overall morbidity and mortality. Human cardiovascular and renal systems exhibit a complex network of positive and negative feedback that is reflected in the control of vascular tone via angiotensin II (Ang II) based signaling. This review will examine in some depth, the multiple components and processes that control the status and reflect the health of these various cardiovascular and renal systems, such as pathways associated to monomeric G proteins, RhoA/Rho kinase system and ERK, oxidative stress and NO balance. It will specifically emphasize the "yin-yang" nature of Ang II signaling by comparing and contrasting the effects and activity of various systems, pathways and components found in hypertension to those found in Gitelman's and Bartter's syndromes (GS/BS), two rare autosomal recessive tubulopathies characterized by electrolytic imbalance, metabolic alkalosis, sodium wasting and prominent activation of the renin-angiotensin-aldosterone system. Notwithstanding the activation of the renin-angiotensin-aldosterone system, GS/BS are normo-hypotensive and protected from cardiovascular-renal remodeling and therefore can be considered the mirror image, the opposite of hypertension.