Dual effects of RAS blockade on blood pressure and podocyte function.
There is no question about the contributory risk of hypertension in morbidity and mortality from cardiovascular (CV) disease and chronic kidney disease (CKD). Another independent risk factor for CV disease and CKD is proteinuria, which is most commonly caused by dysfunction of the kidney glomerular filter, in particular of the podocyte. Podocytes are highly differentiated pericyte-like cells that are essential to normal kidney function. Moreover, loss of podocytes is a hallmark of diabetic and nondiabetic progressive CKD. Recent data point to an important role for the renin-angiotensin system (RAS) and calcium signaling in the structural and functional integrity of podocytes. Given this scenario, it is desirable to treat hypertension with agents targeting the RAS, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (Ang II) type 1-receptor blockers (ARB). These agents have proven effects on lowering blood pressure (BP) and can reduce podocyte injury. Here we review the dual effects of RAS blockade on BP and on podocyte function and emphasize BP-dependent and BP-independent effects of this regimen.
Reiser
Jochen
J
Division of Nephrology, Program in Glomerular Disease, Massachusetts General Hospital and Harvard Medical School, CNY-149, 13th Street, Suite 8214, Boston, MA 02129, USA. jreiser@partners.org
Mundel
Peter
P
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D050199:Podocytes / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors