Angiotensin-(1-7) in the basolateral amygdala attenuates the cardiovascular response evoked by acute emotional stress.

The basolateral amygdala (BLA) plays a critical role in mediating physiological responses to emotional stress. Recent data suggest that angiotensin-(1-7) [Ang-(1-7)] can act centrally attenuating the cardiovascular response to acute stress. We investigated whether Ang-(1-7) in the BLA plays a role in the cardiovascular response to emotional stress. Under anesthesia, guide cannulas were implanted into the BLA of Wistar rats. Five days later, the femoral artery was cannulated for mean arterial pressure (MAP) and heart rate (HR) recordings. Microinjections of Ang-(1-7) (5 or 50 pmol), the Mas receptor antagonist A-779 (100 pmol), Ang-(1-7)+A-779 (50 + 100 pmol, respectively), or vehicle (NaCl 0.9%, control) were performed after 24h and rats were then submitted to stress trials. Injection of Ang-(1-7) into the BLA blocked the tachycardia (ΔHR: vehicle 135 ± 23 vs. Ang-(1-7) 9 ± 12 bpm; P<0.05) and the pressor response (ΔMAP: vehicle 28 ± 3 mmHg vs. Ang-(1-7) 6 ± 2 mmHg; P<0.05) produced by air jet stress. These effects were completely reversed by A-779 (ΔHR: 109 ± 11 bpm; ΔMAP: 18 ± 2 mmHg). Ang-(1-7) into the BLA also attenuated the pressor response evoked by cage-switch stress paradigm. These findings indicate that Ang-(1-7) can act in the BLA through the Mas receptors modulating the cardiovascular response evoked by emotional stress.

Synchronized activation of sympathetic vasomotor, cardiac, and respiratory outputs by neurons in the midbrain colliculi.

The superior and inferior colliculi are believed to generate immediate and highly coordinated defensive behavioral responses to threatening visual and auditory stimuli. Activation of neurons in the superior and inferior colliculi have been shown to evoke increases in cardiovascular and respiratory activity, which may be components of more generalized stereotyped behavioral responses. In this study, we examined the possibility that there are "command neurons" within the colliculi that can simultaneously drive sympathetic and respiratory outputs. In anesthetized rats, microinjections of bicuculline (a GABA(A) receptor antagonist) into sites within a circumscribed region in the deep layers of the superior colliculus and in the central and external nuclei of the inferior colliculus evoked a response characterized by intense and highly synchronized bursts of renal sympathetic nerve activity (RSNA) and phrenic nerve activity (PNA). Each burst of RSNA had a duration of ∼300-400 ms and occurred slightly later (peak to peak latency of 41 ± 8 ms) than the corresponding burst of PNA. The bursts of RSNA and PNA were also accompanied by transient increases in arterial pressure and, in most cases, heart rate. Synchronized bursts of RSNA and PNA were also evoked after neuromuscular blockade, artificial ventilation, and vagotomy and so were not dependent on afferent feedback from the lungs. We propose that the synchronized sympathetic-respiratory responses are driven by a common population of neurons, which may normally be activated by an acute threatening stimulus.

Contribution of infralimbic cortex in the cardiovascular response to acute stress.

The infralimbic region of the medial prefrontal cortex (IL) modulates autonomic and neuroendocrine function via projections to subcortical structures involved in the response to stress. We evaluated the contribution of the IL to the cardiovascular response evoked by acute stress. Under anesthesia (80 mg/kg ketamine-11.5 mg/kg xylazine), rats were implanted with telemetry probes or arterial lines for recording heart rate and blood pressure. Guide cannulas were implanted to target the IL for microinjection of muscimol (100 pmol/100 nl), N-methyl-d-aspartate (NMDA) (6 pmol/100 nl), or vehicle (100 nl). Microinjection of muscimol, an agonist of GABA(A) receptors, into the IL had no effect on stress-evoked cardiovascular and thermogenic changes in any of the paradigms evaluated (cage switch, restraint plus air-jet noise, or air-jet stress). However, microinjection of the excitatory amino acid NMDA into the IL attenuated the pressor and tachycardic response to air-jet stress. Pretreatment with the selective NMDA antagonist dl-2-amino-5-phosphonopentanoic acid (AP-5, 100 pmol/100 nl) blocked the effect of NMDA on the cardiovascular response to air-jet stress. We conclude that 1) the IL region is not tonically involved in cardiovascular or thermogenic control during stress or under baseline conditions, and 2) activation of NMDA receptors in the IL can suppress the cardiovascular response to acute stress exposure.

Evidence that central action of paraquat interferes in the dipsogenic effect of Ang II.

Paraquat is a widely used herbicide that may have central neurotoxic actions. In this study we investigated whether administration of paraquat in the central nervous system interferes with the physiological role of angiotensin II in regulating blood pressure, water intake and thermogenesis. Under tribromoethanol anesthesia (250 mg/kg, i.p.) guide canulas were implanted into the cerebral ventricle of male Wistar rats ( congruent with 300g) for microinjections of drugs. Four days later, a catheter was placed into the femoral artery to enable recording of cardiovascular parameters. After 24h, paraquat (38 or 44 nmol/2 microl), angiotensin II (Ang II, 1 nmol/2 microl) or the cholinergic agonist, carbachol (4 nmol/2 microl) were administered intracerebroventricular (icv) and physiological effects were measured. We observed that the dipsogenic action evoked by Ang II (8+/-2 ml) was markedly attenuated by previous icv injection of either 38 or 44 nmol paraquat (3+/-1 ml; P<0.05). However, the dipsogenic effect evoked by carbachol was not altered by pretreatment with paraquat (before 8+/-1 vs. after 6+/-2; P>0.05). Cardiovascular and thermogenic responses evoked by Ang II were not altered by paraquat. These results suggest that paraquat might selectively interfere with the drinking behavior mediated by the renin-angiotensin system in the central nervous system.