Involvement of kinin B1 receptor and oxidative stress in sensory abnormalities and arterial hypertension in an experimental rat model of insulin resistance

C. Lungu, Jenny Pena Dias, C. Estevão de França, B. Ongali, D. Regoli, F. Moldovan, R. Couture

Research output: Contribution to journalArticle

Abstract

Diabetes Mellitus leads to pain neuropathy and cardiovascular complications which remain resistant to current therapies involving the control of glycaemia. This study aims at defining the contribution of kinin B1 receptor (B1R) and the oxidative stress on sensory abnormalities and arterial hypertension in a rat model of insulin resistance. Rats were fed with 10% d-glucose for a chronic period of 12-14 weeks and the impact of a diet supplemented with α-lipoic acid, a potent antioxidant, was determined on tactile and cold allodynia, arterial hypertension and the expression of kinin B1R (real-time PCR and autoradiography) in several tissues. Acute effects of brain penetrant (LF22-0542) and peripherally acting (R-715) B1R antagonists were also assessed. Glucose-fed rats exhibited tactile and cold allodynia along with increases in systolic blood pressure between 4 and 12 weeks; these alterations were alleviated by α-lipoic acid. The latter regimen also decreased significantly increased plasma levels of insulin and glucose and insulin resistance (HOMA index) at 14 weeks. B1R mRNA was virtually absent in liver, aorta, lung, kidney and spinal cord isolated from control rats, yet B1R mRNA was markedly increased in all tissues in glucose-fed rats. Up-regulated B1R mRNA and B1R binding sites (spinal cord) were significantly reduced by α-lipoic acid in glucose-fed rats. LF22-0542 reduced tactile and cold allodynia (3 h) and reversed arterial hypertension (3-48 h) in glucose-fed rats. R-715 abolished tactile and cold allodynia but had not effect on blood pressure. Data suggest that the oxidative stress contributes to the induction and up-regulation of B1R in the model of insulin resistance induced by glucose feeding. The over expressed B1R contributes centrally to arterial hypertension and in the periphery to sensory abnormalities.

Original languageEnglish (US)
Pages (from-to)375-387
Number of pages13
JournalNeuropeptides
Volume41
Issue number6
DOIs
StatePublished - Dec 1 2007
Externally publishedYes

Fingerprint

Kinins
Insulin Resistance
Oxidative Stress
Theoretical Models
Hypertension
Glucose
Hyperalgesia
Thioctic Acid
R 715
Blood Pressure
Messenger RNA
Spinal Cord
Autoradiography
Aorta
Real-Time Polymerase Chain Reaction
Diabetes Mellitus
Up-Regulation
Antioxidants
Binding Sites
Insulin

Keywords

  • α-Lipoic acid
  • Allodynia
  • Arterial hypertension
  • B receptor
  • Bradykinin
  • Diabetes mellitus
  • Insulin resistance
  • Neuropathy
  • Oxidative stress

ASJC Scopus subject areas

  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Involvement of kinin B1 receptor and oxidative stress in sensory abnormalities and arterial hypertension in an experimental rat model of insulin resistance. / Lungu, C.; Pena Dias, Jenny; França, C. Estevão de; Ongali, B.; Regoli, D.; Moldovan, F.; Couture, R.

In: Neuropeptides, Vol. 41, No. 6, 01.12.2007, p. 375-387.

Research output: Contribution to journalArticle

Lungu, C. ; Pena Dias, Jenny ; França, C. Estevão de ; Ongali, B. ; Regoli, D. ; Moldovan, F. ; Couture, R. / Involvement of kinin B1 receptor and oxidative stress in sensory abnormalities and arterial hypertension in an experimental rat model of insulin resistance. In: Neuropeptides. 2007 ; Vol. 41, No. 6. pp. 375-387.
@article{f88fb76233f940d39783f9afebb125c0,
title = "Involvement of kinin B1 receptor and oxidative stress in sensory abnormalities and arterial hypertension in an experimental rat model of insulin resistance",
abstract = "Diabetes Mellitus leads to pain neuropathy and cardiovascular complications which remain resistant to current therapies involving the control of glycaemia. This study aims at defining the contribution of kinin B1 receptor (B1R) and the oxidative stress on sensory abnormalities and arterial hypertension in a rat model of insulin resistance. Rats were fed with 10{\%} d-glucose for a chronic period of 12-14 weeks and the impact of a diet supplemented with α-lipoic acid, a potent antioxidant, was determined on tactile and cold allodynia, arterial hypertension and the expression of kinin B1R (real-time PCR and autoradiography) in several tissues. Acute effects of brain penetrant (LF22-0542) and peripherally acting (R-715) B1R antagonists were also assessed. Glucose-fed rats exhibited tactile and cold allodynia along with increases in systolic blood pressure between 4 and 12 weeks; these alterations were alleviated by α-lipoic acid. The latter regimen also decreased significantly increased plasma levels of insulin and glucose and insulin resistance (HOMA index) at 14 weeks. B1R mRNA was virtually absent in liver, aorta, lung, kidney and spinal cord isolated from control rats, yet B1R mRNA was markedly increased in all tissues in glucose-fed rats. Up-regulated B1R mRNA and B1R binding sites (spinal cord) were significantly reduced by α-lipoic acid in glucose-fed rats. LF22-0542 reduced tactile and cold allodynia (3 h) and reversed arterial hypertension (3-48 h) in glucose-fed rats. R-715 abolished tactile and cold allodynia but had not effect on blood pressure. Data suggest that the oxidative stress contributes to the induction and up-regulation of B1R in the model of insulin resistance induced by glucose feeding. The over expressed B1R contributes centrally to arterial hypertension and in the periphery to sensory abnormalities.",
keywords = "α-Lipoic acid, Allodynia, Arterial hypertension, B receptor, Bradykinin, Diabetes mellitus, Insulin resistance, Neuropathy, Oxidative stress",
author = "C. Lungu and {Pena Dias}, Jenny and Fran{\cc}a, {C. Estev{\~a}o de} and B. Ongali and D. Regoli and F. Moldovan and R. Couture",
year = "2007",
month = "12",
day = "1",
doi = "10.1016/j.npep.2007.09.005",
language = "English (US)",
volume = "41",
pages = "375--387",
journal = "Neuropeptides",
issn = "0143-4179",
publisher = "Churchill Livingstone",
number = "6",

}

TY - JOUR

T1 - Involvement of kinin B1 receptor and oxidative stress in sensory abnormalities and arterial hypertension in an experimental rat model of insulin resistance

AU - Lungu, C.

AU - Pena Dias, Jenny

AU - França, C. Estevão de

AU - Ongali, B.

AU - Regoli, D.

AU - Moldovan, F.

AU - Couture, R.

PY - 2007/12/1

Y1 - 2007/12/1

N2 - Diabetes Mellitus leads to pain neuropathy and cardiovascular complications which remain resistant to current therapies involving the control of glycaemia. This study aims at defining the contribution of kinin B1 receptor (B1R) and the oxidative stress on sensory abnormalities and arterial hypertension in a rat model of insulin resistance. Rats were fed with 10% d-glucose for a chronic period of 12-14 weeks and the impact of a diet supplemented with α-lipoic acid, a potent antioxidant, was determined on tactile and cold allodynia, arterial hypertension and the expression of kinin B1R (real-time PCR and autoradiography) in several tissues. Acute effects of brain penetrant (LF22-0542) and peripherally acting (R-715) B1R antagonists were also assessed. Glucose-fed rats exhibited tactile and cold allodynia along with increases in systolic blood pressure between 4 and 12 weeks; these alterations were alleviated by α-lipoic acid. The latter regimen also decreased significantly increased plasma levels of insulin and glucose and insulin resistance (HOMA index) at 14 weeks. B1R mRNA was virtually absent in liver, aorta, lung, kidney and spinal cord isolated from control rats, yet B1R mRNA was markedly increased in all tissues in glucose-fed rats. Up-regulated B1R mRNA and B1R binding sites (spinal cord) were significantly reduced by α-lipoic acid in glucose-fed rats. LF22-0542 reduced tactile and cold allodynia (3 h) and reversed arterial hypertension (3-48 h) in glucose-fed rats. R-715 abolished tactile and cold allodynia but had not effect on blood pressure. Data suggest that the oxidative stress contributes to the induction and up-regulation of B1R in the model of insulin resistance induced by glucose feeding. The over expressed B1R contributes centrally to arterial hypertension and in the periphery to sensory abnormalities.

AB - Diabetes Mellitus leads to pain neuropathy and cardiovascular complications which remain resistant to current therapies involving the control of glycaemia. This study aims at defining the contribution of kinin B1 receptor (B1R) and the oxidative stress on sensory abnormalities and arterial hypertension in a rat model of insulin resistance. Rats were fed with 10% d-glucose for a chronic period of 12-14 weeks and the impact of a diet supplemented with α-lipoic acid, a potent antioxidant, was determined on tactile and cold allodynia, arterial hypertension and the expression of kinin B1R (real-time PCR and autoradiography) in several tissues. Acute effects of brain penetrant (LF22-0542) and peripherally acting (R-715) B1R antagonists were also assessed. Glucose-fed rats exhibited tactile and cold allodynia along with increases in systolic blood pressure between 4 and 12 weeks; these alterations were alleviated by α-lipoic acid. The latter regimen also decreased significantly increased plasma levels of insulin and glucose and insulin resistance (HOMA index) at 14 weeks. B1R mRNA was virtually absent in liver, aorta, lung, kidney and spinal cord isolated from control rats, yet B1R mRNA was markedly increased in all tissues in glucose-fed rats. Up-regulated B1R mRNA and B1R binding sites (spinal cord) were significantly reduced by α-lipoic acid in glucose-fed rats. LF22-0542 reduced tactile and cold allodynia (3 h) and reversed arterial hypertension (3-48 h) in glucose-fed rats. R-715 abolished tactile and cold allodynia but had not effect on blood pressure. Data suggest that the oxidative stress contributes to the induction and up-regulation of B1R in the model of insulin resistance induced by glucose feeding. The over expressed B1R contributes centrally to arterial hypertension and in the periphery to sensory abnormalities.

KW - α-Lipoic acid

KW - Allodynia

KW - Arterial hypertension

KW - B receptor

KW - Bradykinin

KW - Diabetes mellitus

KW - Insulin resistance

KW - Neuropathy

KW - Oxidative stress

UR - http://www.scopus.com/inward/record.url?scp=36048964528&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36048964528&partnerID=8YFLogxK

U2 - 10.1016/j.npep.2007.09.005

DO - 10.1016/j.npep.2007.09.005

M3 - Article

C2 - 17988733

AN - SCOPUS:36048964528

VL - 41

SP - 375

EP - 387

JO - Neuropeptides

JF - Neuropeptides

SN - 0143-4179

IS - 6

ER -