Genetic forms of human hypertension.
Our basic understanding of sodium mechanisms provides unique insights into epithelial transport processes, and unusual clinical syndromes can arise from mutations of these ion transporters. These genetic disorders affect sodium balance, with both sodium-retaining and sodium-wasting conditions being the consequence. A major focus of such studies has been the epithelial sodium channel, which can be activated by mutations in the channel subunits or mineralocorticoid receptor, and changes in the response to or production of mineralocorticoids. As a result, there are now clearly defined Mendelian syndromes in which epithelial sodium channel activity is 'dysregulated', with the subsequent development of systemic hypertension with suppressed plasma renin activity that can be attributed to a primary renal mechanism. Applying these insights to the far more common disorder of low renin hypertension may shed new light on the underlying pathophysiology of this common form of human hypertension, and more clearly define the interactions of dietary constituents such as sodium and potassium in the regulation of blood pressure.
Warnock
D G
DG
Departments of Medicine and Physiology and Biophysics, and Nephrology Research and Training Center, University of Alabama at Birmingham, 35294-0007, USA. dwarnock@nrtc.dom.uab.edu
D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D053503:Epithelial Sodium Channels; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008901:Mineralocorticoids / Q000502:physiology; D009154:Mutation; D011110:Polymorphism, Genetic; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D012083:Renin / Q000172:deficiency; D015222:Sodium Channels / Q000235:genetics; D012982:Sodium, Dietary / Q000008:administration & dosage; D013577:Syndrome
D053503:Epithelial Sodium Channels; D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D015222:Sodium Channels; D012982:Sodium, Dietary; D019405:Cytochrome P-450 CYP11B2; D012083:Renin