Degeneration of capsaicin-sensitive sensory nerves leads to increased salt sensitivity through enhancement of sympathoexcitatory response.
We have previously shown that neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat responsive to a salt load with an increase in blood pressure and a decrease in natriuretic response. To test the hypothesis that the enhanced sympathoexcitatory response to a high salt intake contributes to the development of hypertension in this model, newborn Wistar rats were given 50 mg/kg capsaicin and/or 80 mg/kg guanethidine subcutaneously. Control rats were treated with vehicle. After the weaning period, male rats were grouped as the following and given a high sodium diet (4%) for 2 weeks: capsaicin and guanethidine coadministration (CAP-GUA), capsaicin only (CAP), guanethidine only (GUA), and vehicle control (CON). Norepinephrine concentrations in the atrium were significantly lower in CAP-GUA and GUA than in CON rats (P<0.05). Twenty-four-hour urine and sodium excretions were significantly lower in CAP than in CAP-GUA, GUA, and CON rats (P<0.05). Mean arterial pressure (mm Hg) was significantly higher in CAP (180+/-10) than in CAP-GUA (106+/-1), GUA (133+/-5), and CON (122+/-3) rats (P<0.05). Thus, sympathectomy restores the natriuretic response to a high salt intake and prevents the development of salt-sensitive hypertension induced by sensory denervation. These data indicate that sensory nerves counterbalance the prohypertensive effect of the sympathetic nerves to maintain blood pressure within normal range during salt loading.
Department of Medicine and Pharmacology and Toxicology, Michigan State University, East Lansing, USA. donna.wang@ht.msu.edu
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Lookingland
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D006973:Hypertension / Q000517:prevention & control; D007279:Injections, Subcutaneous; D008297:Male; D009318:Natriuresis; D009410:Nerve Degeneration; D011188:Potassium / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000473:pathology
D012982:Sodium, Dietary; D012964:Sodium; D011188:Potassium; D002211:Capsaicin; D006145:Guanethidine