2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline and cobaltous-chloride

In the present study, we investigated the role played by the hypothalamic paraventricular nucleus (PVN) in the modulation of cardiac baroreflex activity in unanesthetized rats. Bilateral microinjections of the nonselective neurotransmission blocker CoCl(2) into the PVN decreased the reflex bradycardic response evoked by blood pressure increases, but had no effect on reflex tachycardia evoked by blood pressure decreases. Bilateral microinjections of the selective NMDA glutamate receptor antagonist LY235959 into the PVN caused effects that were similar to those observed after microinjections of CoCl(2), decreasing reflex bradycardia without affecting tachycardic response. The microinjection of the selective non-NMDA glutamate receptor antagonist NBQX into the PVN did not affect the baroreflex activity. Also, the microinjection of L-glutamate into the PVN increased the reflex bradycardia, an effect opposed to that observed after PVN treatment with CoCl(2) or LY235959, and this effect of L-glutamate was blocked by PVN pretreatment with LY235959. LY235959 injected into the PVN after i.v. treatment with the selective beta(1)-adrenoceptor antagonist atenolol still decreased the reflex bradycardia. Taken together, our results suggest a facilitatory influence of the PVN on the bradycardic response of the baroreflex through activation of local NMDA glutamate receptors and a modulation of the cardiac parasympathetic activity.

Topics: Adrenergic beta-Antagonists; Animals; Baroreflex; Blood Pressure; Bradycardia; Cobalt; Excitatory Amino Acid Antagonists; Glutamic Acid; Heart; Isoquinolines; Male; Microinjections; Parasympathetic Nervous System; Paraventricular Hypothalamic Nucleus; Quinoxalines; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate

In the present study, we report the effect of insular cortex (IC) ablation caused by bilateral microinjection of the non-selective synaptic blocker CoCl(2) on cardiac baroreflex response in unanesthetized rats as well as the involvement of local glutamatergic neurotransmission. Unilateral (left or right) microinjection of CoCl(2) (1 nmol/ 100 nL) did not affect the bradycardiac response to blood pressure increase evoked by intravenous infusion of phenylephrine nor the tachycardiac response to blood pressure decrease caused by intravenous infusion of sodium nitroprusside, 10 min after CoCl(2). Bilateral microinjection of CoCl(2) into IC decreased the magnitude of reflex bradycardia without affecting tachycardiac responses. Baroreflex activity returned to control values 60 min after CoCl(2) microinjection, confirming its reversible effect. Further we studied the possible involvement of IC-glutamatergic neurotransmission in baroreflex modulation. We observed that bilateral microinjection of the selective NMDA receptor antagonist LY235959 (4 nmol/100 nL) into the IC decreased the magnitude of reflex bradycardia without affecting tachycardiac responses. IC treatment with the selective non-NMDA antagonist NBQX (4 nmol/100 nL) did not affect baroreflex activity. The results suggest that synapses within the IC have a tonic excitatory influence on the baroreflex parasympathetic component. Moreover, the present data suggest that local NMDA-receptors are involved in the IC-mediated tonic excitatory influence on baroreflex parasympathetic activity.

Topics: Anesthetics; Animals; Antihypertensive Agents; Autonomic Pathways; Baroreflex; Blood Pressure; Bradycardia; Cerebral Cortex; Cobalt; Efferent Pathways; Excitatory Amino Acid Antagonists; Glutamic Acid; Heart Rate; Isoquinolines; Neurons; Nitroprusside; Quinoxalines; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission

Summary 1. In the present study, we investigated the effects of inhibition of the lateral hypothalamus (LH) neurotransmission with bilateral microinjection of CoCl(2), a non-selective blocker of neurotransmission, on modulation of cardiac baroreflex responses in conscious rats as well as the involvement of LH glutamatergic neurotransmission in this modulation. 2. Reflex bradycardiac and tachycardiac responses to blood pressure increases (following i.v. infusion of phenylephrine) or decreases (following i.v. infusion of sodium nitroprusside) were investigated in conscious male Wistar rats. Responses were evaluated before and after microinjection of 1 nmol/100 nL CoCl(2), 2 nmol/100 nL 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulphonamide (NBQX; a selective non-N-methyl-d-aspartate (NMDA) glutamate receptor antagonist) or different doses (2, 4 or 8 nmol/100 nL) of the selective NMDA glutamate receptor antagonist LY235959. 3. Microinjection of CoCl(2) into the LH had no effect on the tachycardiac baroreflex response, but did evoke a decrease in the reflex bradycardia caused by increases in blood pressure. Microinjection of NBQX into the LH had a similar effect on reflex bradycardia as CoCl(2), but had no effect on the tachycardiac response. Microinjection of increasing doses of LY235959 into the LH had no effect on the cardiac baroreflex response. 4. In conclusion, the data suggest that the LH has a tonic facilitatory influence on the parasympathetic component of the baroreflex. The results also indicate that this facilitatory influence is mediated by local LH glutamatergic neurotransmission through non-NMDA glutamatergic receptors.

Topics: Animals; Baroreflex; Blood Pressure; Bradycardia; Cobalt; Excitatory Amino Acid Antagonists; Hypothalamic Area, Lateral; Isoquinolines; Male; Microinjections; Quinoxalines; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission; Tachycardia

Microinjection of l-glutamate (l-glu: 1, 3, 10 and 30nmol/100nL) into the lateral hypothalamus (LH) caused dose-related depressor and bradycardiac responses. The cardiovascular response to l-glu stimulation of the LH was blocked by pretreatment of the ventrolateral portion of the periaqueductal gray matter (vlPAG) with CoCl2 (1mM/100nL), indicating the existence of a synaptic relay of the hypotensive pathway in that area. Furthermore, the response to l-glu was blocked by pretreatment of the vlPAG with 2nmol/100nL of the selective NMDA-receptor antagonist LY235959 and was not affected by pretreatment with 2nmol/100nL of the selective non-NMDA-receptor antagonist NBQX, suggesting a mediation of the hypotensive response by NMDA receptors in the vlPAG. In conclusion, our results indicate that the hypotensive pathway activated by microinjection of l-glu into the LH involves a NMDA synaptic relay in the vlPAG.

Topics: Anesthesia; Animals; Blood Pressure; Cobalt; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Glutamic Acid; Heart Rate; Hypothalamic Area, Lateral; Isoquinolines; Male; Microinjections; Nerve Block; Periaqueductal Gray; Quinoxalines; Rats; Rats, Wistar