Cardiovascular and autonomic phenotype of db/db diabetic mice

Exp Physiol. 2009 Jun;94(6):648-58. doi: 10.1113/expphysiol.2008.046474. Epub 2009 Feb 13.

Abstract

The db/db mice serve as a good model for type 2 diabetes characterized by hyperinsulinaemia and progressive hyperglycaemia. There are limited and conflicting data on the cardiovascular changes in this model. The aim of the present study was to characterize the cardiovascular and autonomic phenotype of male db/db mice and evaluate the role of angiotensin II AT(1) receptors. Radiotelemetry was used to monitor 24 h blood pressure (BP) in mice for 8 weeks. Parameters measured were mean arterial pressure (MAP), heart rate (HR) and their variabilities. In 8-week-old db/db mice, the MAP and BP circadian rhythms were not different from age-matched control mice, while HR and locomotor activity were decreased. With ageing, MAP gradually increased in db/db mice, and the 12 h light values did not dip significantly from the 12 h dark periods. In 14-week-old mice, MAP was increased during light (101 +/- 1 versus 117 +/- 2 mmHg, P < 0.01; control versus db/db mice) and dark phases (110 +/- 1.7 versus 121 +/- 3.1 mmHg, P < 0.01; control versus db/db mice). This increase in MAP was associated with a significant increase in plasma angiotensin-converting enzyme activity and angiotensin II levels. Chronic treatment with losartan (10 mg kg(-1) day(-1)) blocked the increase in MAP in db/db mice, with no effect in control animals. Spectral analysis was used to monitor autonomic cardiovascular function. The circadian rhythm observed in systolic arterial pressure variance and its low-frequency component in control mice was absent in db/db mice. There were no changes in HR variability and spontaneous baroreflex sensitivity between control and db/db mice. The results document an age-related increase in MAP in db/db mice, which can be reduced by antagonism of angiotensin II AT(1) receptors, and alterations in autonomic balance and components of the renin-angiotensin system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / physiology
  • Angiotensin II / blood
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Autonomic Nervous System / drug effects
  • Autonomic Nervous System / physiopathology*
  • Baroreflex / genetics
  • Baroreflex / physiology
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Cardiovascular System / drug effects
  • Cardiovascular System / physiopathology*
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology
  • Diabetes Complications / drug therapy
  • Diabetes Complications / etiology
  • Diabetes Complications / genetics
  • Diabetes Complications / physiopathology
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Disease Models, Animal
  • Heart Rate / physiology
  • Hypertension / drug therapy
  • Hypertension / etiology
  • Hypertension / genetics
  • Hypertension / physiopathology
  • Losartan / pharmacology
  • Male
  • Mice
  • Mice, Mutant Strains
  • Motor Activity / physiology
  • Peptidyl-Dipeptidase A / blood
  • Phenotype
  • Receptor, Angiotensin, Type 1 / physiology
  • Receptors, Leptin / genetics*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Receptor, Angiotensin, Type 1
  • Receptors, Leptin
  • leptin receptor, mouse
  • Angiotensin II
  • Peptidyl-Dipeptidase A
  • Losartan