A systems pharmacology model predicted that glomerular pressure increases with salt intake in salt-sensitive hypertension and provided mechanistic insights into differential responses to antihypertensives.
How do ACE inhibitors, thiazide diuretics, and calcium channel blockers differentially affect blood pressure and glomerular pressure in salt-sensitive versus salt-resistant hypertension models?
A systems pharmacology model provides mechanistic insights into why salt-sensitive hypertensive patients experience increased glomerular pressure and respond differently to various antihypertensive classes.
Salt-sensitivity (SS) refers to changes in blood pressure in response to changes in sodium intake. SS individuals are at greater risk for developing kidney disease, and also respond differently to antihypertensive therapies compared to salt-resistant (SR) individuals. In this study we used a systems pharmacology model of renal function (presented in a companion article) to evaluate the ability of proposed mechanisms to produce salt-sensitivity. The model reproduced previously published data on renal functional changes in response to salt-intake, and also predicted that glomerular pressure, a variable that is not easily evaluated clinically but is a key factor in renal injury, increases with salt intake in SS hypertension. We then used the model to generate mechanistic insight into the differential blood pressure and glomerular pressure responses to angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, and calcium channel blockers observed in SS and SR hypertension.
Hallow et al. (Sat,) conducted a other in Salt-Sensitive Hypertension. Systems pharmacology model was evaluated on Renal functional changes, blood pressure, and glomerular pressure responses. A systems pharmacology model predicted that glomerular pressure increases with salt intake in salt-sensitive hypertension and provided mechanistic insights into differential responses to antihypertensives.