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), CA
P-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 s
odium diet + candesartan + PD 123319 (CAP-HS-CAN-PD). Mean arterial pressur
e (MAP) was measured by carotid arterial catheterization. Urinary Na+ conce
ntrations were determined by using a flame atomic absorption spectrophotome
ter. Levels of calcitonin gene-related peptide (CGRP) in dorsal root gangli
a (DRG) and plasma renin activity (PRA) were determined by radioimmunoassay
Results CGRP contents in DRG were decreased by capsaicin (P < 0.05). MAP wa
s 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 highe
r 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 attenuate
s the development of hypertension in salt-loaded rats neonatally treated wi
th capsaicin, indicating that the AT2 receptor contributes to the increase
in blood pressure. (C) 2001 Lippincott Williams & Wilkins.