Blockade of NK-1 receptors in the lateral commissural nucleus tractus solitarii of awake rats had no effect on the cardiovascular responses to chemoreflex activation

Abstract

The neurotransmission of the chemoreflex in the nucleus tractus solitarii (NTS), particularly of the sympatho-excitatory component, is not completely understood. There is evidence that substance P may play a role in the neurotransmission of the chemoreflex in the NTS. Microinjection of substance P (50 pmol/50 nl, N = 12, and 5 nmol/50 nl, N = 8) into the commissural NTS of unanesthetized rats produced a significant increase in mean arterial pressure (101 ± 1 vs 108 ± 2 and 107 ± 3 vs 115 ± 4 mmHg, respectively) and no significant changes in heart rate (328 ± 11 vs 347 ± 15 and 332 ± 7 vs 349 ± 13 bpm, respectively) 2 min after microinjection. Previous treatment with WIN, an NK-1 receptor antagonist (2.5 nmol/50 nl), microinjected into the NTS of a specific group of rats, blocked the pressor (11 ± 5 vs 1 ± 2 mmHg) and tachycardic (31 ± 6 vs 4 ± 3 bpm) responses to substance P (50 pmol/50 nl, N = 5) observed 10 min after microinjection. Bilateral microinjection of WIN into the lateral commissural NTS (N = 8) had no significant effect on the pressor (50 ± 4 vs 42 ± 6 mmHg) or bradycardic (-230 ± 16 vs -220 ± 36 bpm) responses to chemoreflex activation with potassium cyanide (iv). These data indicate that the activation of NK-1 receptors by substance P in the NTS produces an increase in baseline mean arterial pressure and heart rate. However, the data obtained with WIN suggest that substance P and NK-1 receptors do not play a major role in the neurotransmission of the chemoreflex in the lateral commissural NTS.

Cardiovascular responses to substance P in the nucleus tractus solitarii: microinjection study in conscious rats

“…Lower doses of SP (0.001 and 0.01 nmol/100 nl) had no cardiovascular effects. The pressor/tachycardic effect of a dose close to the ED 50 was blocked by previous injection of a NK-1 antagonist as reported previously (44). Most studies in anesthetized animals using low doses of SP (0.00007-0.06 nmol) have reported short lasting hypotension (4, Fig.…”

Chronic intermittent hypoxia reduces neurokinin-1 (NK1) receptor density in small dendrites of non-catecholaminergic neurons in mouse nucleus tractus solitarius

“…The transmitter within these NK 1 -containing neurons may include glutamate, since (1) microinjection of SP in the cNTS results in blood pressure elevation (Zhang et al, 2000), and (2) increased blood pressure may result from activation of NTS glutamatergic neurons projecting to sympathoexcitatory neurons in the rostral ventrolateral medulla (RVLM; (Mazzone et al, 1997; Mauad and Machado, 1998; Babic and Ciriello, 2004; Bailey et al, 2004). However, the SP-induced elevation in blood pressure is not blocked by bilateral microinjection of an NK 1 receptor antagonist in the lateral cNTS (Zhang et al, 2000), suggesting a lack of direct involvement of these receptors in mediating chemoreflexes. In contrast, NK 1 receptors in the NTS are highly implicated in bronchopulmonary reflexes that defend the lungs against injury from inhaled agents by the induction of apnea, cough, and hypotension (Mutoh et al, 2000).…”

“…The excitatory transmitters in these sensory vagal inputs include glutamate and substance P (SP; Helke et al, 1980; Douglas et al, 1982; Kalia et al, 1984; Kawano and Chiba, 1984; Kawano and Masuko, 1997; Kawano and Masuko, 1995; Lindefors et al, 1986; Srinivasan et al, 1991), a tachykinin peptide that preferentially acts through G protein coupled neurokinin-1 (NK 1 ) receptors (Rodier et al, 2001; Rico et al, 2003; Bonham et al, 2004). Moreover, brainstem SP-induced activation of NK 1 receptors can modulate cardiovascular and respiratory responses evoked through the respective baro- and chemoreceptor reflexes (Gillis et al, 1980; Lindefors et al, 1986; Hall et al, 1989; Massari et al, 1998; Zhang et al, 2000; Nattie and Li, 2002). These observations are consistent with the electron microscopic autoradiographic localization of NK 1 receptor binding sites to postsynaptic neurons in the NTS (Jia et al, 1996; Baude and Shigemoto, 1998).…”

Colocalization of neurokinin-1, N-methyl-d-aspartate, and AMPA receptors on neurons of the rat nucleus tractus solitarii

“…Of the numerous neurotransmitters found in the NTS, glutamate is the principal excitatory neurotransmitter and has been recognized to play a pivotal role in regulating cardiovascular functions in the NTS (Seagard et al, 2001;Talman et al, 1980;Talman, 1997). Studies have also suggested that substance P (SP), acting at neurokinin-1 (NK1) receptors (Feldman, 1995;Zhang et al, 2000), plays a role in neuromodulation of cardiovascular control in the NTS (Boscan et al, 2002;Gillis et al, 1980;Potts, 2006), though a role for the peptide in transmission of baroreflex signals has been controversial. For example, administration into the NTS of SP or agonists for NK1 receptors evoked contradictory arterial baroreceptor responses (Bauman et al, 2002;Carter and Lightman, 1985;Feldman, 1995;Kubo and Kihara, 1987;Nagashima et al, 1989;Talman and Reis, 1981).…”