Antihypertensive mechanisms underlying a novel salt-sensitive hypertensive model induced by sensory denervation

Abstract

A novel model of hypertension recently developed in our laboratory shows that neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat responsive to a salt load with a significant rise in blood pressure. To determine the role of the renin-angiotensin system and the sympathetic nervous system in the development of hypertension in this model, newborn Wistar rats were given capsaicin 50 mg/kg SC on the first and second days of life. Control rats were treated with vehicle. After they were weaned, male rats were divided into 6 groups and subjected to the following treatments for 2 weeks: control+high sodium diet (4%) (CON-HS), capsaicin+normal sodium diet (0.5%) (CAP-NS), capsaicin+high sodium diet (CAP-HS), capsaicin+high sodium diet+losartan (10 mg/kg per day) (CAP-HS-LO), capsaicin+high sodium diet+prazosin (3 mg/kg per day) (CAP-HS-PR), and capsaicin+high sodium diet+hydralazine (10 mg/kg per day) (CAP-HS-HY). Levels of calcitonin gene-related peptide in dorsal root ganglia were decreased by capsaicin treatment (P<0.05). Both tail-cuff systolic blood pressure and mean arterial pressure were higher in CAP-HS and CAP-HS-PR than in CON-HS, CAP-NS, CAP-HS-LO, and CAP-HS-HY (P<0.05). The 24-hour urinary volume and sodium excretion were increased when a high sodium diet was given (P<0.05), but they were lower in CAP-HS, CAP-HS-LO, CAP-HS-PR, and CAP-HS-HY than in CON-HS (P<0.05). Urinary potassium excretion was not different among all 6 groups. We conclude that blockade of the angiotensin type 1 receptor with losartan but not antagonism of the alpha1-adrenoreceptor with prazosin prevents the development of salt-sensitive hypertension induced by sensory denervation. Sensory denervation impairs urinary sodium and water excretion in response to a high sodium intake, regardless of blood pressure, suggesting that sensory innervation plays a direct role in regulating the natriuretic response to sodium loading.