Role of the glutamatergic system of ventrolateral periaqueductal gray (vlPAG) in the cardiovascular responses in normal and hemorrhagic conditions in rats

Abstract

Objectives: Periaqueductal gray (PAG) is a mesencephalic area divided into four columns including ventrolateral periaqueductal gray (vlPAG). vlPAG plays a role in cardiovascular regulation during normal and hemorrhagic (Hem) conditions. Due to presence of glutamate in this area, we evaluated the effect of glutamatergic receptors of this area on cardiovascular activity in normotensive and hypovolemic Hem rats.

Materials and methods: Animals were divided into twelve groups: saline (vehicle), Glutamate, GYK52466 (non-NMDA receptor antagonist), and MK801 (NMDA receptor antagonist) with and without Glu microinjected into vlPAG in normal and Hem conditions. Following the femoral artery cannulating and microinjecting, changes (Δ) of heart rate (HR), systolic blood pressure (SBP), and mean arterial pressure (MAP) were recorded via a PowerLab unit.

Results: In normotensive conditions, microinjection of Glu increased ΔMAP, ΔSBP, and ΔHR (P<0.001). MK-801 and GYKI-52466 nonsignificant reduced cardiovascular responses than vehicle while their changes were significant compared with glutamate (P<0.001). Co-injection of GYKI- 52466 with Glu did not significantly reduce ΔSBP and ΔMAP induced by Glu (P>0.05) but co-injection of MK-801 with Glu significantly attenuate these effects(P<0.01). In Hem, Glu increased ΔSBP, ΔMAP, and ΔHR (P<0.05). GYKI-52466 alone did not change cardiovascular responses but MK-801 decreased ΔSBP than Hem (P<0.01). Co-injection of GYKI-52466 with Glu had significant(P<0.05) but MK-801 with Glu had no significant effect compared with Hem (P>0.05).

Conclusion: The glutamatergic system of vlPAG increases cardiovascular values that are mostly mediated through the NMDA receptor. Since vlPAG is well known as an inhibitory region, it seems that glutamate does not have a noteworthy cardiovascular role in vlPAG during Hem and normal conditions.

Keywords: Blood pressure; Cardiovascular system; Glutamic acid; Hemorrhage; Periaqueductal gray.

Figure 1

Time course of ∆SBP (A), ∆MAP(B), and ∆HR (C), after microinjection of saline, glutamate, and NMDA (MK) and non-NMDA antagonist (GYK) of glutamate receptor into vlPAG nucleus. Data were expressed as mean±SEM; n= 6 (repeated measures ANOVA). ∆MAP: mean arterial pressure, ∆SBP: systolic blood pressure, ∆HR: heart rate, vehicle: saline microinjection, Glu: glutamate, GYK: GYKI-52466, MK: MK801. ***: P<0.001, **: P<0.01, and *: P<0.05 vs vehicle group, ###:P<0.001, ##: P<0.01, and #: P<0.05 vs Glu group

Figure 2

Peak changes of ∆SBP (a), ∆MAP(b), and ∆HR (c), after microinjection of saline, glutamate, NMDA (MK), and non-NMDA antagonist (GYK) of glutamate receptor and their co-injection with Glu into vlPAG nucleus. Data were expressed as mean±SEM; n= 6 (one-way ANOVA). ∆MAP: mean arterial pressure, ∆SBP: systolic blood pressure, ∆HR: heart rate, vehicle: saline microinjection, Glu: glutamate, GYK: GYKI-52466, MK: MK801. ***: P<0.001, **: P<0.01, and *: P<0.05 vs vehicle group, ###: P<0.001, ##: P<0.01, and #: P<0.05 vs Glu group

Figure 3

Time course of ∆SBP (A), ∆MAP(B), and ∆HR (C) after microinjection of saline, glutamate, GYK the non-NMDA antagonist of glutamate receptor, and co-injection of GYK and Glu into vlPAG nucleus in hemorrhagic condition. Data were expressed as mean±SEM; n= 6 (repeated measures ANOVA). ∆MAP: Mean arterial pressure, ∆SBP: Systolic blood pressure, ∆HR: Heart rate, vehicle: saline microinjection, Glu: glutamate, GYK: GYKI-52466. Differences with P-value <0.05 were considered significant. ***: P<0.001, **: P<0.01, and *: P<0.05 vs vehicle group, ###: P<0.001, ##: P<0.01, and #: P<0.05 vs Hem+saline group and ^^^: P<0.001, ^^: P<0.01, and ^: P<0.05 vs Glu group

Figure 4

Time course of ∆SBP (A), ∆MAP(B), and ∆HR (C), after microinjection of the saline, glutamate, MK the NMDA antagonist of glutamate receptor, and co-injection of MK and Glu into vlPAG nucleus in hemorrhagic condition. Data were expressed as mean±SEM; n= 6 (repeated measures ANOVA). ∆MAP: mean arterial pressure, ∆SBP: systolic blood pressure, ∆HR: heart rate, vehicle: saline microinjection, Glu: glutamate, GYK: GYKI-52466, MK: MK801. Differences with P-value <0.05 were considered significant. ***: P<0.001, **: P<0.01, and *: P<0.05 vs vehicle group, ###: P<0.001, ##: P<0.01, and #: P<0.05 vs Hem+saline group and ^^^: P<0.001, ^^: P<0.01, and ^: P<0.05 vs Glu group

Figure 5

Peak changes of ∆SBP (A), ∆MAP (B), and ∆HR (C) after microinjection of saline, glutamate, NMDA (MK), and non-NMDA antagonist (GYK) of glutamate receptor and co-injection of them with Glu into vlPAG nucleus in hemorrhagic condition. Data were expressed as mean±SEM; n=6 (one-way ANOVA). ∆MAP: mean arterial pressure, ∆SBP: systolic blood pressure, ∆HR: heart rate, vehicle: saline microinjection, Glu: glutamate, GYK: GYKI-52466, MK: MK801. Differences with P-value<0.05 were considered significant. ***: P<0.001, **: P<0.01, and *: P<0.05 vs vehicle group, ###: P<0.001, ##: P<0.01, and #: P<0.05 vs Hem+saline group and ^^^: P<0.001, ^^: P<0.01, and ^: P<0.05 vs Glu group