Effects Of Central Cholinergic System At RVLM And CeA On Carotid Sinus Baroreceptor Reflex And Its Mechanism

Objective: To investigate the effects of central cholinergic system on carotid sinus baroreceptor reflex (CSR) and its mechanism.Method: The bilateral carotid sinus areas were isolated under anesthesia with pentobarbital sodium in the Sprague?Dawley rats. The intracarotid sinus pressure (ISP) and mean arterial pressure (MAP) were simultaneously recorded, via pressure transducers connected with the catheters which were inserted into the left or right isolated carotid sinus and femoral artery respectively. ISP was set at the level of 0 mmHg to eliminate the effect of initial internal pressure of the carotid sinus on the CSR function. To trigger CSR, the ISP was quickly elevated from 0 mmHg to 280 mmHg in a stepwise manner—40 mmHg which were added at every step for over 4 sec, and then ISP returned to 0 mmHg in similar steps. The original data of ISP and corresponding MAP were fitted to a modified logistic equation with five parameters to obtain the ISP-MAP, ISP-Gain relationship curves and the CSR characteristic parameters, which were statistically compared and analyzed separately. Under the condition of no influence on the basic levels of the artery blood pressure, the effects and the potential regulatory mechanism of the central cholinergic system on the CSR were studied by microinjection of the cholinesterase inhibitors, physostigmine (PHY) and various selective cholinergic receptors antagonists into the lateral ventricles and / or nuclei (rostral ventrolateral medulla, RVLM and central nucleus of the amygdala, CeA).Results:1. The effects of physostigmine (PHY) into the lateral ventricles on CSRRespective intracerebroventricular microinjection, (i. c. v.) of PHY with three different doses (low, medium and high doses ) significantly shifted the ISP-MAP relationship curve upwards, and moved the middle part of ISP-Gain relationship curve downwards, and reduced parameters the MAP changing range and reflex maximum gain (Gmax), but increased parameters such as set point, saturation pressure (SP) and ISP at Gmax (ISPGmax) (P <0.05), which suggest that the central acetylcholine (ACh) can result in a inhibitory rapid resetting of CSR function.2. Effects of preceding microinjection of different cholinergic receptor antagonists into the rostral ventrolateral medulla on CSR changes resulted from i. c. v. PHYStandalone microinjection of selective cholinergic receptors antagonists, prienzepine (PRZ, for M1 receptor) or methoctramine (MTR, for M2 receptor) or hexamethonium (HEX, for N1 receptor) into the rostral ventrolateral medulla (RVLM) with given dose, neither cause their basic level of arterial blood pressure significantly change nor affect the CSR reflecting the sensitivity and function (P >0.05).The effects of pretreatment with different cholinergic receptor antagonists, PRZ or MTR using corresponding dose into the RVLM on CSR, could attenuate CSR resetting resulted from RVLM microinjection in some degrees, which remarkably moved the ISP-MAP relationship curve downwards (P <0.05), and shifted the middle part of ISP-Gain relationship curve upwards (P <0.05), and increased parameters the MAP changing range and Gmax (P <0.05), but decreased parameters such as saturation pressure (SP) and ISPGmax (P <0.05). The catabatic effects of pretreatment with MTR on CSR resetting induced by i.c.v. PHY were more than those of PRZ (P <0.05), pretreatment of HEX with same dose into the RVLM had no effects on CSR resetting induced by i.c.v. PHY (P >0.05).3. Effects of preceding microinjection of different cholinergic receptor antagonists into the central nucleus of the amygdala on CSR changes induced by i. c. v. PHYStandalone microinjection of selective cholinergic receptors antagonists, PRZ or MTR, or HEX into the central nucleus of the amygdala (CeA) with given dose, also neither cause their basic level of arterial blood pressure significantly change nor affect the CSR reflecting the sensitivity and function (P >0.05).The effects of pretreatment with different cholinergic receptor antagonists, PRZ or MTR using corresponding dose into the CeA on CSR changes induced by i. c. v. PHY were similar to those of pretreatment into the RVLM, and attenuating action of pretreatment with PRZ into the CeA on CSR resetting induced by i.c.v. PHY were less than that of MTR (P <0.05), however, pretreatment of HEX with same dose into the CeA also had no effects on CSR resetting induced by i.c.v. PHY (P >0.05). Conclusion:1. Microinjection of the cholinesterase inhibitors, physostigmine into the lateral ventricle obviously results in a inhibitory rapid resetting of CSR function with a dose-dependent manner.2. Standalone microinjection of selective cholinergic receptors antagonists, PRZ or MTR, or HEX into the rostral ventrolateral medulla (RVLM) and central nucleus of the amygdala (CeA) neither cause their basic level of arterial blood pressure significantly change nor affect the CSR reflecting the sensitivity and function.3. Pretreatments of cholinergic receptor antagonists, PRZ or MTR into the rostral ventrolateral medulla may attenuate CSR resetting resulted from i.c.v. PHY, the catabatic effects of the selective M2 receptor antagonist are more obvious than those of the selective M1 receptor antagonist, and the selective N1 receptor antagonist has no effect, which indicate that the M1 and M2 receptors in the nuclei around the lateral ventricle mediate effects of central cholinergic system on carotid sinus baroreceptor reflex resetting, and the M2 receptor may play more important roles than M1 receptor. And the descending cholinergic pathway from the hypothalamus to RVLM might be related to effects of central cholinergic system on CSR.4. The effects of the pretreatment with M1 or M2 receptors antagonist into the CeA on CSR resetting resulted from i.c.v. PHY, are similar to the above-mentioned conclusion 3, the catabatic effects of the selective M2 receptor antagonist are more obvious than those of the selective M1 receptor antagonist, and the selective N1 receptor antagonist has no effect. It suggest that M1 and M2 receptors, especially M2 receptor in the CeA may be involved in the effects of central cholinergic system on carotid sinus baroreceptor reflex resetting, and the cholinergic pathway from the hypothalamus to CeA might be related to effects of central cholinergic system on CSR.