The kidney and hypertension: over 70 years of research

The crucial role of the kidneys in regulation of systemic blood pressure has been known for more than 70 years. A multitude of studies have described the regulatory mechanisms behind this interaction, and elucidate why kidney disease is such a rampant and difficult form of secondary hypertension. Historically, renal hypertension has primarily been described as derangements of the renin-angiotensin-aldosterone system (RAAS), and salt and volume retention. Renally mediated hypertension involves the activation of RAAS leading to angiotensin II-mediated vaso-constriction, and aldosterone-mediated salt retention. The increased sodium retention and volume expansion seen in kidney disease is accompanied by a failure to autoregulate the peripheral vasculature, leading to hypertension. An-giotensin II and aldosterone also cause increased inflammation and endothelial dysfunction, and volume retention leads to the elaboration of ouabain-like compounds that contribute to increased total peripheral resistance. More recently, studies have shown that activation of renal afferent pathways connecting with specific brain nuclei involved in the noradrenergic control of blood pressure appears to play a substantial role. This article will review the classic pa-radigms, as well as new and emerging paradigms linking the kidney with blood pressure.