Disease Information

General Information of the Disease (ID: DIS00289)

• Name: Hypertension
• ICD: ICD-11: BA00

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Saralasin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Natriuretic peptides A (ANF) [1]

• Resistant Disease: Hypertension [ICD-11: BA00.Z]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Saralasin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Two-kidney,one-clip hypertensive rat; Rattus norvegicus
• Experiment for Drug Resistance: Pressure measurement
• Mechanism Description: Saralasin-resistant rats exhibited a decreased number of vascular ANF binding sites in both mesenteric arteries and aorta. We conclude that through modulation of its glomerular and vascular receptors, ANF may contribute to the differential sodium handling of saralasin-sensitive and -resistant 2K1C hypertensive rats and to the reduced vascular responsiveness to ANF observed in the saralasin-resistant hypertensive rats.

Triamterene

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epithelial sodium channel (ENAC) [2]

• Resistant Disease: Edema [ICD-11: MG29.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Triamterene
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: In addition to pharmacokinetic effects, compensatory upregulation of sodium transporters not blocked by the diuretic also contributes to diuretic resistance. In patients with CKD, plasma aldosterone levels may be elevated even in the presence of normal plasma renin activity and normal serum potassium concentrations. Elevated plasma levels of both angiotensin II and aldosterone can activate sodium transporters in the distal nephron, including the Na+/Cl cotransporter and ENaC.

References

• Ref 1: Glomerular and vascular atrial natriuretic factor receptors in saralasin-sensitive and -resistant two-kidney, one-clip hypertensive rats .Circ Res. 1988 Sep;63(3):563-71. doi: 10.1161/01.res.63.3.563. 10.1161/01.res.63.3.563
• Ref 2: Diuretic Resistance .Am J Kidney Dis. 2017 Jan;69(1):136-142. doi: 10.1053/j.ajkd.2016.08.027. Epub 2016 Nov 1. 10.1053/j.ajkd.2016.08.027