FIGURE 25.

Mutations in proteins expressed by thick ascending limbs that cause hypertension. Loss of function mutations in the basolateral Ca²⁺-sensing receptor (CaSR) would decrease the inhibitory effect of this receptor on Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2), while gain of function mutations in ClC-Kb channels would also lead to increases in NKCC2 activity. Mutations in the CYP4A11 gene may decrease 20-hydroxyeicosatetraenoic acid (20-HETE) levels and, therefore, its inhibitory effects on NaCl reabsorption in the thick ascending limb.