Role of AT1 and AT2 receptor subtypes in salt-sensitive hypertension induced by sensory nerve degeneration.
OBJECTIVE: To define the role of the type 1 angiotensin II (AT1) and type II (AT2) receptors in the development of salt-sensitive hypertension induced by sensory nerve degeneration. DESIGN AND METHODS: Neonatal Wistar rats were given capsaicin 50 mg/kg s.c. on the first and second days of life. After weaning, male rats were divided into six groups and treated for 3 weeks with: control + high sodium diet (4%, CON-HS), capsaicin pretreatment + normal sodium diet (0.5%, CAP-NS), CAP-HS, CAP + HS + candesartan (10 mg/kg per day) (CAP-HS-CAN), CAP + HS + PD 123319 (30 mg/kg per day) (CAP-HS-PD), and capsaicin pretreatment + high sodium diet + candesartan + PD 123319 (CAP-HS-CAN-PD). Mean arterial pressure (MAP) was measured by carotid arterial catheterization. Urinary Na+ concentrations were determined by using a flame atomic absorption spectrophotometer. Levels of calcitonin gene-related peptide (CGRP) in dorsal root ganglia (DRG) and plasma renin activity (PRA) were determined by radioimmunoassay. RESULTS: CGRP contents in DRG were decreased by capsaicin (P < 0.05). MAP was higher in CAP-HS rats compared with all the other groups (P < 0.05). The 24 h urine and sodium excretion increased when a high salt diet was given, but they were lower in CAP-HS and CAP-HS-CAN than in CON-HS (P < 0.05). PRA was suppressed in CON-HS and CAP-HS compared with CAP-NS, but it was higher in CAP-HS than in CON-HS (P < 0.05). CONCLUSION: Insufficiently suppressed PRA by high salt intake may contribute to increased salt sensitivity and account for effectiveness of candesartan in lowering blood pressure in this model. Furthermore, PD 123319 attenuates the development of hypertension in salt-loaded rats neonatally treated with capsaicin, indicating that the AT2 receptor contributes to the increase in blood pressure.[1]References
- Role of AT1 and AT2 receptor subtypes in salt-sensitive hypertension induced by sensory nerve degeneration. Huang, Y., Wang, D.H. J. Hypertens. (2001) [Pubmed]
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