Effect of Lisinopril and Verapamil on Angiopoietin 2 and Endostatin in Hypertensive Diabetic Patients with Nephropathy: A Randomized Trial

Horm Metab Res. 2021 Jul;53(7):470-477. doi: 10.1055/a-1517-6643. Epub 2021 Jul 19.

Abstract

Angiogenesis is a multistep process implicated in the pathophysiology and progression of diabetic nephropathy (DN). Angiotensin-converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) have an important role in DN. We performed a randomized-controlled trial of lisinopril alone (an ACEI) or in combination with verapamil (a CCB) as a therapy for DN in type 2 diabetes mellitus (T2DM) patients with hypertension (HTN) and urinary albumin creatinine ratio (UACR) (30-300 mg/g) also to evaluate their effect on UACR, the angiogenic proteins: Angiopoietin 2 (Ang-2) and Endostatin (EST). Forty T2DM patients with microalbuminuria, aged 45-65 years were included. Patients were randomly assigned into group 1 receiving oral lisinopril and group 2 receiving oral lisinopril and verapamil once daily. After 3 months follow-up fasting blood glucose (FPG), HbA1c, lipid profile, UACR, serum urea and creatinine levels were assessed. EST and Ang-2 were measured using ELISA technique. Baseline Ang-2 and EST levels were elevated in both groups compared with controls (p<0.001). After follow-up, group 2 had significantly decreased FPG, HbA1c, UACR, EST and Ang-2 compared with their baseline levels (p<0.001 for all comparisons) and with group 1 (p<0.001). No adverse reactions were reported. Baseline EST and Ang-2 were positively correlated to UACR (r=0.753, p<0.001) (r=0.685, p<0.001). Lisinopril/verapamil combination enhanced glycemic control and kidney function via diminishing EST and Ang-2. This combination can be considered as a safe and effective approach for early stage nephropathy therapy in T2DM.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Drug Therapy, Combination
  • Endostatins / genetics
  • Endostatins / metabolism*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation / drug effects*
  • Humans
  • Hypertension / physiopathology*
  • Lisinopril / pharmacology*
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Vasodilator Agents / pharmacology
  • Verapamil / pharmacology*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Endostatins
  • VPS51 protein, human
  • Vasodilator Agents
  • Vesicular Transport Proteins
  • Verapamil
  • Lisinopril