Dorsal hippocampus cholinergic and nitrergic neurotransmission modulates the cardiac baroreflex function in rats.

Hippocampus is a limbic structure involved in the baroreflex and chemoreflex control that receives extensive cholinergic input from basal forebrain. Hippocampal muscarinic receptors activation by acetylcholine might evoke nitric oxide synthesis, which is an important neuromodulator of cardiovascular responses. Thus, we hypothesize that cholinergic and nitrergic neurotransmission within the DH modulates the baroreflex and chemoreflex function. We have used vasoactive drugs (phenylephrine and sodium nitroprusside), and potassium cyanide infused peripherally to induce, respectively, baroreflex or chemoreflex responses in awake animals. Bilateral injection into the DH of the acetylcholinesterase inhibitor (neostigmine) reduced baroreflex responses. Meanwhile, the non-selective muscarinic receptor antagonist (atropine) or the M1-selective muscarinic receptor antagonist increased baroreflex responses (pirenzepine). Furthermore, the neuronal nitric oxide synthase inhibitor (N-propyl) or the intracellular NO scavenger (carboxy-PTIO) increased baroreflex responses, as well as the selective inhibitor of NO-sensitive guanylyl cyclase (ODQ), increased the baroreflex responses. Besides, bilateral administration of an ineffective dose of a neuronal nitric oxide synthase inhibitor abolished the reduction in the baroreflex responses evoked by an acetylcholinesterase inhibitor. On the other hand, we have demonstrated that hippocampal cholinergic neurotransmission did not influence the chemoreflex function. Taken together, our findings suggest that nNOS-derived nitric oxide in the DH participates in acetylcholine-evoked baroreflex responses.

Effect of chronic stress on cardiovascular and ventilatory responses activated by both chemoreflex and baroreflex in rats.

Chronic stress results in physiological and somatic changes. It has been recognized as a risk factor for several types of cardiovascular dysfunction and changes in autonomic mechanisms, such as baroreflex and chemoreflex activity. However, the effects of different types of chronic stress on these mechanisms are still poorly understood. Therefore, in the present study, we investigated, in adult male rats, the effect of repeated restraint stress (RRS) or chronic variable stress (CVS) on baroreflex, chemoreflex and heart rate variability in a protocol of 14 days of stress sessions. Exposure to RRS and CVS indicated no changes in the basal level of either arterial pressure or heart rate. However, RRS and CVS were able to attenuate sympathovagal modulation and spontaneous baroreflex gain. Additionally, only RRS was able to increase the power of the low-frequency band of the systolic blood pressure spectrum, as well as the slope of linear regression of baroreflex bradycardic and tachycardic responses induced by vasoactive compounds. Additionally, our study is one of the first to show that exposure to RRS and CVS decreases the magnitude of the pressor response and potentiates respiratory responses to chemoreflex activation, which can trigger cardiovascular and respiratory pathologies. Furthermore, the basal respiratory parameters, such as minute ventilation and tidal volume, were significantly decreased by both protocols of chronic stress. However, only CVS increased the basal respiratory frequency. In this way, the findings of the present study demonstrate the impact of chronic stress in terms of not only depressive-like behavior but also alterations of the autonomic baroreflex responses and cardiocirculatory variability (systolic blood pressure and pulse interval).Our results provide evidence that chronic stress promotes autonomic dysregulation, and impairment of baroreflex, chemoreflex and heart rate variability.

Ventral hippocampus modulates bradycardic response to peripheral chemoreflex activation in awake rats.

NEW FINDINGS: What is the central question of this study? Does reversible synaptic inactivation by CoCl2 in the dorsal (DH) or ventral (VH) portions of the hippocampus have a modulatory effect on cardiovascular and respiratory responses evoked by chemoreflex activation in awake rats? What is the main finding and its importance? Using i.v. infusion of KCN to activate the peripheral chemoreflex before and after microinjection of CoCl2 into VH, we showed that the bradycardic response was increased, but not the pressor and tachypnoeic responses even if the tidal volume had been increased. Thus, VH but not DH may be involved in the modulation of the parasympathoexcitatory component of the peripheral chemoreflex. In rats, peripheral chemoreflex activation evokes pressor and bradycardic responses as well as a tachypnoeic response. Studies have shown that limbic structures, such as the hippocampus, can modulate autonomic reflexes. Evidence suggests that the dorsal (DH) and the ventral (VH) portions of the hippocampus are structurally and functionally distinct; therefore, in the present study we tested the hypothesis that local neurotransmission of the DH and VH are involved in the neural pathways of the cardiovascular and ventilatory responses to chemoreflex activation. Thus, the goal of the present study was to compare the chemoreflex responses elicited by i.v. injection of KCN (40 µg per rat) in awake rats before and after DH and VH synaptic transmission was temporarily inhibited by bilateral microinjections of 500 nl of the unspecific synapse blocker, CoCl2 (1  mm). Bilateral inhibition of VH, but not DH, 10 min before KCN infusion was able to enhance the bradycardic response (P < 0.05), with no changes in the typical pressor and tachypnoeic responses evoked by chemoreflex activation (P > 0.05). Furthermore, the tidal volume was significantly increased (P < 0.05) even though no other respiratory parameter had been significantly changed (P > 0.05), suggesting that VH can exert a tonic modulatory action on tidal volume. Therefore, the present study reports, for the first time, that DH neurotransmission did not exert an influence on chemoreflex responses, whereas VH mediates, at least in part, the parasympathoexcitatory component of the peripheral chemoreflex.