Premium
Role of angiotensin AT1 receptors in the development of cardiovascular dysfunction in type 2 diabetic (db/db) mice
Author(s) -
Kanakamedala Keerthy,
Senador Danielle,
Chen Yanfang,
Morris Mariana,
Elased Khalid M.
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1246-d
Cardiovascular disease is a long term complication of diabetes, which remains a leading cause of mortality and morbidity. There is evidence for activation of the renin angiotensin system (RAS) in diabetic animals and humans. We have shown previously that a high fructose diet in mice produces glucose tolerance and increased blood pressure (BP). This goal of this study was to investigated BP control and the role of the angiotensin AT1 receptors in the db / db model of type 2 diabetes. Mice (8–9 weeks) were implanted with carotid telemetric probes and 24 hr mean arterial pressure (MAP), heart rate (HR) and activity were monitored every week for up to 20 weeks. At early age (9–10 weeks), db / db mice developed significant hyperglycemia and hyperinsulinemia which was not associated with changes in MAP. HR and activity were decreased. MAP gradually increased with age in db / db diabetic mice. By 12 weeks MAP in diabetics was higher as compared to their lean controls both during day (101 ± 1 vs 117 ± 2 mmHg, p<0.01) and night (110 ± 1.7 vs 121 ± 3.1 mmHg, p<0.01). Chronic treatment with losartan (10 mg/kg/day in drinking water) for 12 weeks significantly blocked the progression of the MAP changes in diabetic mice during day (102 ± 4 vs 117 ± 2.5 mmHg, p<0.01) and night (104 ± 4 vs 126 ± 2.2 mmHg, p<0.01). Results document the increase in BP in db / db diabetic mice and the importance of Ang AT1 receptors in mediating the BP changes in this murine model of type 2 diabetes.