Excitatory amino acid receptor blockade within the caudal pressor area and rostral ventrolateral medulla alters cardiovascular responses to nucleus raphe obscurus stimulation in rats

Abstract

Pressor responses elicited by stimulation of the nucleus raphe obscurus (NRO) depend on the integrity of the rostral ventrolateral medulla (RVLM). Therefore, to test the participation of excitatory amino acid (EAA) receptors in the cardiovascular responses evoked by NRO stimulation (1 ms, 100 Hz, 40-70 µA, for 10 s), the EAA antagonist kynurenic acid (Kyn) was microinjected at different sites in the ventrolateral medullar surface (2.7 nmol/200 nl) of male Wistar rats (270-320 g, N = 39) and NRO stimulation was repeated. The effects of NRO stimulation were: hypertension (DMAP = +43 ± 1 mmHg, P<0.01), bradycardia (DHR = -30 ± 7 bpm, P<0.01) and apnea. Bilateral microinjection of Kyn into the RVLM, which did not change baseline parameters, almost abolished the bradycardia induced by NRO stimulation (DHR = -61 ± 3 before vs -2 ± 3 bpm after Kyn, P<0.01, N = 7). Unilateral microinjection of Kyn into the CVLM did not change baseline parameters or reduce the pressor response to NRO stimulation (DMAP = +46 ± 5 before vs +48 ± 5 mmHg after Kyn, N = 6). Kyn bilaterally microinjected into the caudal pressor area reduced blood pressure and heart rate and almost abolished the pressor response to NRO stimulation (DMAP = +46 ± 4 mmHg before vs +4 ± 2 mmHg after Kyn, P<0.01, N = 7). These results indicate that EAA receptors on the medullary ventrolateral surface play a role in the modulation of the cardiovascular responses induced by NRO stimulation, and also suggest that the RVLM participates in the modulation of heart rate responses and that the caudal pressor area modulates the pressor response following NRO stimulation.

Pressor responses to nasal stimulation are unaltered after disrupting the CPA

“…Glycine, GABA and glutamate are relatively ubiquitous neurotransmitters in the central nervous system; glycine and GABA are inhibitory while glutamate is excitatory. The concentration and volume of glycine (1M; 50nl) and the GABA agonist muscimol (2mM; 50nl) used in the present study were similar to those used by other investigators of the CPA (Campos et al, 1999; Natarajan et al, 2000; Silva et al, 2002). Glycine and GABA are active for relatively short periods, being measured in minutes (Aprison et al, 1970; Possas et al, 1994; Hupe et al, 1999), whereas muscimol, a GABA agonist, is active for hours (Arikan et al, 2002).…”

“…However, the larger relative declines in resting MABP seen by others after injections of GABA (Possas et al, 1994) or glycine (Campos Jr et al, 1994) into the most caudal ventrolateral medulla may have been due to either the larger injection volumes used in these studies, or their more caudal and medial injection sites. Also, injections of kynurenate into the CPA had no effect on resting MABP in one study (Campos Jr et al, 1994) but significantly reduced blood pressure in another (Silva et al, 2002). The smaller declines in resting MABP after injections of muscimol in the present study were similar to those seen by others (Natarajan et al, 2000).…”

“…It has been reported that relatively large injections of kynurenate into the CPA blocks the cardiorespiratory responses induced by electrical stimulation of nucleus raphe obscurus (Silva et al, 2002), but the CPA does not mediate the pressor response to carotid occlusion (Possas et al, 1994). We investigate herein a role of the CPA for the increase in arterial blood pressure seen in a nasopharyngeal reflex.…”

Role of the caudal pressor area in the regulation of sympathetic vasomotor tone

“…In rabbits, CPA inhibition caused a similar decrease in arterial pressure and almost abolished renal sympathetic nerve activity (22). Furthermore, bilateral microinjections of kynurenic acid into the CPA reduced the pressor response to stimulation of nucleus raphe obscurus (23). These data suggest that the CPA is important for maintaining the sympathetic vasomotor tone.…”

Responses of opioid and serotonin containing medullary raphe neurons to electroacupuncture

“…These regions are involved in regulation of blood pressure during cardiovascular activation (e.g., defense reaction), but do not exert tonic control of blood pressure (Coleman and Dampney, 1995). Stimulation of different raphe nuclei may increase or decrease blood pressure in different species, likely due to predominant activation of excitatory or inhibitory groups of neurons (Blessing and Nalivaiko, 2000; Coleman and Dampney, 1995; McCall, 1988; McCall and Clement, 1989; Silva et al, 2002). The medullary raphe has been shown to modulate blood pressure through its effects on sympathetic outflow in the rostral ventrolateral medulla (rVLM) as well as through its direct projections to the spinal cord (Larsen et al, 2000; Coleman and Dampney, 1995; Dean and Bago, 2002; Loewy, 1981).…”