Enhanced activity of carotid body chemoreceptors in rabbits with heart failure: role of nitric oxide

An enhanced peripheral chemoreflex has been documented in patients with chr onic heart failure (CHF). This study aimed to examine the characteristics o f carotid body (CB) chemoreceptors in response to isocapnic hypoxia in a ra bbit model of pacing-induced CHF and to evaluate the possible role that nit ric oxide (NO) plays in the altered characteristics. The chemosensitive cha racteristics of the CB were evaluated by recording single-unit activity fro m the carotid sinus nerve in both an intact and a vascularly isolated prepa ration. It was found that the baseline discharge under normoxia (intact pre paration: arterial PO2 90-95 Torr; isolated preparation: PO2 100-110 Torr) and the chemosensitivity in response to graded hypoxia (PO2 40-70 Torr) wer e enhanced in CHF vs. sham rabbits. These alterations were independent of t he CB preparations (intact vs. isolated). NO synthase inhibition by N-omega -nitro-L-arginine increased the baseline discharge and the chemosensitivity in the intact preparation, whereas L-arginine (10(-5) M) inhibited the bas eline discharge and the chemosensitivity in the isolated preparation in sha m but not in CHF rabbits. S-nitroso-N-acetylpenicillamine, an NO donor, inh ibited the baseline discharge and the chemosensitivity in both CB preparati ons in CHF rabbits but only in the isolated preparation in sham rabbits. Th e amount of NO produced in vitro by the CB under normoxia was less in CHF r abbits than in sham rabbits (P < 0.05). NO synthase-positive varicosities o f nerve fibers within the CB were less in CHF rabbits than in sham rabbits (P < 0.05). These data indicate that an enhanced input from CB occurs in th e rabbit model of pacing-induced CHF and that an impairment of NO productio n may contribute to this alteration.