Salt-sensitive hypertension induced by sensory denervation: introduction of a new model.
To test the novel hypothesis that neonatal degeneration of capsaicin-sensitive sensory nerves causes the rat to respond to a salt load with a significant and sustained rise in blood pressure, newborn Wistar rats were given 50 mg/kg capsaicin subcutaneously on the 1st and 2nd day of life. Control rats were treated with vehicle. Immediately after the weanling period, male rats were divided into 4 groups and fed different sodium diets for 2 weeks: capsaicin pretreatment plus high sodium diet (4%, CAP-HS), capsaicin plus normal sodium diet (0.5%, CAP-NS), control plus high sodium diet (CON-HS), and control plus normal sodium diet (CON-NS). Both tail-cuff systolic blood pressure and mean arterial pressure with anesthesia were significantly higher in CAP-HS than in CAP-NS, CON-HS, and CON-NS (P<0.05), but they were not different among the latter 3 groups. Radioimmunoassay revealed that levels of calcitonin gene related peptide in dorsal root ganglia were markedly decreased by capsaicin treatment (P<0.05). Twenty-four-hour urine volume and urine sodium excretion were significantly lower in CAP-HS than in CON-HS but were higher in CAP-HS and CON-HS compared with CAP-NS and CON-NS (P<0.05). Urine potassium excretion was not different among the 4 groups. Thus, this study provides the first evidence that neonatal degeneration of capsaicin-sensitive sensory nerves renders the rat salt-sensitive in terms of blood pressure regulation. Furthermore, our data suggest that neonatal capsaicin treatment may impair renal sodium and water excretion responses to high sodium intake. This model will provide a novel experimental paradigm for exploring underlying molecular mechanisms linked with salt-sensitive hypertension and sensory nerve function.
Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA. dwang@utmb.edu
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D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects*; D002211:Capsaicin / Q000009:adverse effects*; D003714:Denervation; D006973:Hypertension / Q000209:etiology*; D008297:Male; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000187:drug effects*; D012982:Sodium, Dietary / Q000009:adverse effects*
D012982:Sodium, Dietary; D002211:Capsaicin