Sodium and its associated anions are the major determinant of extracellular fluid volume, and renal Na+ reabsorption plays a crucial role in long-term blood pressure control. The goal of this study was to investigate the extent to which inhibitors of transepithelial Na$^+$ transport (T$_{\rm Na}$) along the nephron alter urinary solute excretion and T$_{\rm Na}$ efficiency, and how those effects may vary along different nephron segments. We used the multi-nephron model developed in the companion study [28], which represents detailed transcellular and paracellular transport processes along the nephrons of a rat kidney. We simulated the inhibition of the Na+/H+ exchanger (NHE3), the bumetanide-sensitive Na+-K+-2C- transporter (NKCC2), the Na+-C- cotransporter (NCC), and the amiloride-sensitive Na$^+$ channel (ENaC). Under baseline conditions, NHE3, NKCC2, NCC and ENaC reabsorb 36, 22, 4 and 7\%, respectively, of filtered Na$^+$. The model predicted that NHE3 inhibition substantially reduced proximal tubule T$_{\rm Na}$ and oxygen consumption (Q$_{\rm O2}$). Whole-kidney T$_{\rm Na}$ efficiency, reflected by the number of moles of Na$^+$ reabsorbed per moles of O$_2$ consumed (denoted by T$_{\rm Na}$/Q$_{\rm O2}$), decreased by ~20% with 80% inhibition of NHE3. NKCC2 inhibition simulations predicted a substantial reduction in thick ascending limb T$_{\rm Na}$ and Q$_{\rm O2}$; however, the effect on whole-kidney T$_{\rm Na}$/Q$_{\rm O2}$ was minor. Tubular K+ transport was also substantially impaired, resulting in elevated urinary K$^+$ excretion. The most notable effect of NCC inhibition was to increase the excretion of Na+, K+, and Cl-; its impact on whole-kidney T$_{\rm Na}$ and its efficiency was minor. ENaC inhibition was predicted to have opposite effects on the excretion of Na+ (increased) and K+ (decreased), and to have only a minor impact on whole-kidney T$_{\rm Na}$ and T$_{\rm Na}$/Q$_{\rm O2}$. Overall, model predictions agree well with measured changes in Na+ and K+ excretion in response to diuretics and Na+ transporter mutations.