Received February 26, 2007
Revised March 12, 2007
Accepted after revision March 12, 2007

¹ Dartmouth Medical School

^* To whom correspondence should be addressed. E-mail: james.c.leiter{at}dartmouth.edu.

	Abstract

Inhibition of neurons in the ventral medulla accentuates the respiratory inhibition associated with acute blood pressure elevation in piglets. Activation of presynaptic 5-HT1A receptors inhibits serotonergic neurons in the ventral medulla and caudal raphé, and we tested the hypothesis that administration of 8-OH-DPAT, a 5-HT1A agonist, within the RVM and caudal raphé would enhance baroreceptor mediated inhibition of respiratory activity in decerebrate, neonatal piglets. Baroreceptor stimulation was achieved by inflating a balloon in the distal aorta to elevate carotid blood pressure. After 2-4 control trials of baroreceptor stimulation, each piglet was given either a single intravenous (i.v.) dose of 10µg/kg 8-OH-DPAT or treated by adding 10mM or 30 mM 8-OH-DPAT to the dialysate for ~10 minutes to inhibit serotonergic neurons, after which the baroreceptor stimulation trials were repeated. Baroreceptor stimulation reduced respiratory activity, particularly the respiratory frequency, which diminished from 35.7±3.3 breaths per minute (bpm) to 33.8±3.1 bpm (P < 0.02), and following i.v. 8-OH-DPAT, baroreceptor mediated inhibition of respiratory output was significantly accentuated (P < 0.05); the respiratory frequency declined from 34.5±3.6 bpm to 26.5±2.9 bpm. Increasing aortic blood pressure reduced the respiratory frequency (P < 0.01), but focal dialysis of 10 or 30mM 8-OH-DPAT had, on average, no effect on the ventilatory inhibition associated with an acute elevation of blood pressure. We conclude that activation of 5-HT1A receptors after systemic administration of 8-OH-DPAT enhanced baroreflex mediated inhibition of ventilation, but this effect cannot be attributed to 5-HT1A receptor activation within the RVM and caudal raphé.

Key Words: Baroreceptor, Respiratory control, Serotonin