Effect of Treatment with Peptidase Inhibitors on Vasoactive Peptide Response in Renal Arteries from Diabetic Rats

Abstract

The purpose of this study was to examine the effect of peptidase inhibitors on peptide induced relaxation of renal arteries from diabetic rats. Rats were injected with 60 mg/kg streptozotocin (IP), and treated with α‐lipoic acid (2.5g/kg), Enalapril (500mg/kg), Candoxatril (300mg/kg), AVE7688 (500mg/kg), or Alogliptin (200mg/kg) in the diet for 12 weeks. Tension studies were performed on tertiary branches of renal arteries Acetylcholine and sodium nitroprusside responses were not altered in phenylephrine constricted arteries. Atrial natruretic peptide (ANP) and calcitonin gene related peptide (CGRP) responses were attenuated in arteries from diabetic rats. Responses were improved when rats received the peptidase inhibitors, but not when rats were treated with α‐lipoic acid. Thus, responses to vasoactive peptides are reduced in diabetic rats, and treatment with peptidase inhibitors, improves dilation to these peptides. Supported by VA merits to Drs. Oltman and Yorek. Blood glucose and response to ANP and CGRP (% Relaxation) Group n Glucose (mg/dl) ANP(10nM) CGRP(10nM) Control 11 110 ± 5 97.7 ± 1.8 79.4 ± 5.5 Diabetic 12 578±13* 77.1 ± 4.9* 47.1 ± 5.9* α‐lipoic acid 8 501 ± 33 79. 6 ± 4.9 54.1 ± 6.9 Enalapril 6 570 ± 22 94.8 ± 3.7# 87.5 ± 4.6# Candoxatril 8 546 ± 14 96.7 ± 1.7# 80.4 ± 4.1# Alogliptin 7 536 ± 22 96.2 ± 2.1# 72.3 ± 8.8# AVE7688 7 575 ± 22 94.8 ± 3.3# 77.1 ± 5.9# Control vs Diabetic P ≤ 0.05 Diabetic vs treatment, p ≤ 0.05.