Dorsal hippocampus cholinergic and nitrergic neurotransmission modulates the cardiac baroreflex function in rats
Nilson Carlos Ferreira-Junior1, Davi Campos Lagatta1, Luciana Bärg Kuntze1
1Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
Insights
Cholinergic and nitrergic neurotransmission in the dorsal hippocampus (DH) modulates baroreflex control. Nitric oxide derived from neuronal nitric oxide synthase (nNOS) in the DH is crucial for acetylcholine-evoked baroreflex responses.
Area of Science:
- Neuroscience
- Cardiovascular Physiology
- Neurotransmission
Background:
- The hippocampus, a limbic structure, plays a role in cardiovascular regulation, receiving significant cholinergic input.
- Acetylcholine activation of hippocampal muscarinic receptors may trigger nitric oxide (NO) synthesis, a key neuromodulator of cardiovascular responses.
Purpose of the Study:
- To investigate the role of cholinergic and nitrergic neurotransmission in the dorsal hippocampus (DH) in modulating baroreflex and chemoreflex functions.
- To determine if nitric oxide synthesis in the DH is involved in acetylcholine-mediated cardiovascular responses.
Main Methods:
- Utilized vasoactive drugs (phenylephrine, sodium nitroprusside) and potassium cyanide infusion in awake animals to elicit baroreflex and chemoreflex responses.
- Administered bilateral injections into the DH of acetylcholinesterase inhibitor (neostigmine), muscarinic receptor antagonists (atropine, pirenzepine), and inhibitors of nitric oxide synthesis/signaling (N-propyl, carboxy-PTIO, ODQ).
Main Results:
- Neostigmine reduced baroreflex responses, while atropine and pirenzepine increased them.
- Inhibitors of nitric oxide synthesis and signaling (N-propyl, carboxy-PTIO, ODQ) increased baroreflex responses.
- A neuronal nitric oxide synthase inhibitor abolished the neostigmine-induced reduction in baroreflex responses, and hippocampal cholinergic neurotransmission did not affect chemoreflex function.
Conclusions:
- Cholinergic and nitrergic pathways in the dorsal hippocampus significantly modulate baroreflex control.
- Neuronal nitric oxide synthase (nNOS)-derived nitric oxide in the DH is essential for acetylcholine-evoked baroreflex responses.
- Hippocampal cholinergic neurotransmission does not influence chemoreflex function.
Abstract:
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.
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