The periaqueductal gray (PAG) is a mesencephalic structure that surrounds the cerebral
aqueduct. The PAG was functionally divided into four longitudinal columns: the dorsomedial,
dorsolateral, lateral and the ventrolateral (vlPAG). Microinjection of endocannabinoid
or endovanilloid antagonists into the vlPAG blocked the cardiovascular responses to
a physical stress: hemorrhage. Microinjection of excitatory amino acids into the vlPAG
caused decreases in blood pressure, heart rate, sympathetic activity, as well as antinociception,
quiescence and hyporeactivity. This syndrome is often associated with pathophysiological
conditions such as the loss of large volumes of blood. Experimental studies have established
that in mammals hemodynamic responses to blood loss consist of three phases: Phase
I compensatory normotensive; Phase II decompensatory, hypotensive and phase III recompensatory
post-hemorrhage, when the pressure returns to normal levels. Recent reports have shown
that the endocannabinoid system is associated with the pathophysiology of hypotension
in various forms of shock, including the hemorrhagic. Interestingly, it has been shown
that the hypotension caused by blood loss was prevented by a systemic pretreatment
with the CB1 antagonist SR141716; the CB1 receptors are densely expressed along the
PAG. In the present study, we evaluated the participation of vlPAG CB1 receptors in
the cardiovascular responses evoked by hemorrhage. Local microinjection of AM251 (0.25 nmol), a selective CB1 receptor antagonist, into the vlPAG caused a delayed onset
of the hypotension, when compared to the control and the tachycardia evoked by hemorrhage
was abolished. The pretreatment of the vlPAG with a lower dose of AM251 (0.025 nmol), abolished both the hypotension and the tachycardia caused by hemorrhage. Importantly,
the pretreatment of the vlPAG with both doses of AM251, did not significantly alter
the recompensatory phase of hemorrhage. We consider that the delayed hypotensive response
observed after the pretreatment of vlPAG with the highest dose of AM251 (0.25 nmol), could be due to nonspecific effects of AM251. Much has been investigated on
the interaction between the endocannabinoid system and the vanilloid system. Furthermore,
recent findings indicate that TRPV1 receptors are also expressed in the PAG. Then,
we pretreated the vlPAG with two doses of the transient receptor potential vanilloid
type 1 (TRPV1) antagonist capsazepine (2.5 and 15 nmol). Pretreatment of the vlPAG with 15 nmol of capsazepine significantly reduced the hypotension and tachycardia evoked by
hemorrhage. However, when we microinjected capsazepine at a dose of 2.5 nmol, we observed total blockade of the hypotension and a reduction in the tachycardiac
response evoked by hemorrhage. These data suggest that TRPV1 and CB1 receptors present
in the vlPAG participate in cardiovascular modulation during hemorrhage.
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© 2015 Published by Elsevier Inc.