Deficiency in angiotensin AT1a receptors prevents diabetes-induced hypertension

Wichi R.B.; Farah V.; Chen Y.; Irigoyen M.C.; Morris M.

Deficiency in angiotensin AT1a receptors prevents diabetes-induced hypertension

Tipo

Artigo

Data de publicação

2007

Periódico

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Citações (Scopus)

24

Autores

Wichi R.B.
Farah V.
Chen Y.
Irigoyen M.C.
Morris M.

Resumo

The renin-angiotensin system has been implicated in the etiology of the cardiovascular complications of diabetes. Our studies extend these findings to show a specific role for angiotensin AT1a receptors in mediating diabetes-induced hypertension. Male angiotensin AT1a knockout (AT1aKO) and wild-type (AT1aWT) mice with arterial telemetric catheters were injected with streptozotocin (STZ; 150 mg/kg ip). The STZ dose was selected on the basis of a dose-response experiment in C57/BL mice. Blood glucose, water intake, body weight, blood pressure (BP), and heart rate (HR) were measured over a 2-wk period. Estimates of BP and HR variance (BPV and HRV) and their low- and high-frequency domains were also determined. STZ induced similar levels of hyperglycemia and polydypsia in the groups. Mean arterial pressure (MAP) was increased from 100 ± 6 to 124 ± 6 mmHg in diabetic AT1aWT. MAP was unchanged in AT1aKO (80 ± 4 vs. 85 ± 5 mmHg, basal vs. STZ). Treatment with an ACE inhibitor, captopril, produced a greater reduction in MAP (-18%) in diabetic AT1aWT than in AT1aKO (-3.4%). BPV was lower in AT1aKO (19 ± 0.5 vs. 9 ± 2 mmHg2, AT1aWT vs. AT1aKO). Diabetes reduced BPV but only in AT1aWT (19 ± 0.5 vs. 8 ± 1 mmHg 2, basal vs. STZ). There were no changes in HR in either group. In AT1aKO, STZ increased HRV and its high-frequency domain with no changes seen in AT1aWT. Results document that ANG AT1a receptors are critical in diabetes-induced hypertension and in cardiac autonomic responses. Copyright © 2007 the American Physiological Society.