Diet-induced obesity severely impairs myelinated aortic baroreceptor reflex responses

Diet-induced obesity (DIO) attenuates the arterial cardiac baroreceptor reflex, but the mechanisms and sites of action are unknown. This study tested the hypothesis that DIO impairs central aortic baroreceptor pathways. Normal chow control (CON) and high-fat-chow obesity-resistant (OR) and obesity-prone (OP) rats were anesthetized (inactin, 120 mg/kg) and underwent sinoaortic denervation. The central end of the aortic depressor nerve (ADN) was electrically stimulated to generate frequency-dependent baroreflex curves (5-100 Hz) during selective activation of myelinated (A-fiber) or combined (A- and C-fiber) ADN baroreceptors. A mild stimulus (1 V) that activates only A-fiber ADN baroreceptors induced robust, frequency-dependent depressor and bradycardic responses in CON and OR rats, but these responses were completely abolished in OP rats. Maximal activation of A fibers (3 V) elicited frequency-dependent reflexes in all groups, but a dramatic deficit was still present in OP rats. Activation of all ADN baroreceptors (20 V) evoked even larger reflex responses. Depressor responses were nearly identical among groups, but OP rats still exhibited attenuated bradycardia. In separate groups of rats, the reduced heart rate (HR) response to maximal activation of ADN A fibers (3 V) persisted in OP rats following pharmacological blockade of β(1)-adrenergic or muscarinic receptors, suggesting deficits in both parasympathetic nervous system (PNS) and sympathetic nervous system (SNS) reflex pathways. However, the bradycardic responses to direct efferent vagal stimulation were similar among groups. Taken together, our data suggest that DIO severely impairs the central processing of myelinated aortic baroreceptor control of HR, including both PNS and SNS components.     

Effect of baroreceptor activity on ventilatory response to chemoreceptor stimulation.

This study tested the hypothesis that ventilatory responses to chemoreceptor stimulation are affected by the level of arterial pressure and degree of baroreceptor activation. Carotid chemoreceptors were stimulated by injection of nicotine into the common carotid artery of anesthetized dogs. Arterial pressure was reduced by bleeding the animals and raised by transient occlusion of the abdominal aorta. The results indicate that ventilatory responses to chemoreceptor stimulation were augmented by hypotension and depressed by hypertension. In additional studies we excluded the possibility that the findings were produced by a direct effect of changes in arterial pressure on chemoreceptors. Both carotid bifurcations were perfused at constant flow. In one carotid bifurcation, perfusion pressure was raised to stimulate carotid sinus baroreceptors. In the other carotid bifurcation, pressure was constant and nicotine was injected to stimulate carotid chemoreceptors. Stimulation of baroreceptors on one side attenuated the ventilatory response to stimulation of contralateral chemoreceptors. This inhibition was observed before and after bilateral cervical vagotomy. We conclude that there is a major central interaction between baroreceptor and chemoreceptor reflexes so that changes in baroreceptor activity modulate ventilatory responses to chemoreceptor stimulation.     

大鼠侧脑室内注射组胺对颈动脉窦压力感受性反射的影响及其中枢机制

在50只麻醉的大鼠孤离双侧颈动脉窦区,将不同窦内压（ISP）与其对应的平均动脉压（MAP）值进行Logistic五参数曲线拟合,根据所得ISP-MAP关系曲线及其特征参数,观察侧脑室注射（i.c.v)组胺（HA）对颈动脉窦压力感受性反射（CSR）的影响,并对其作用机制进行了初步探讨。结果如下：（1）i.c.v.HA(100ng)导致ISP-MAP关系曲线显著上移,ISP和增益（Gain)关系曲线中部明显下移,反射参数中阈压（TP）,饱和压（SP）和最大增益时的窦内压（ISPGmax)值增大,MAP反射变动范围（MAPrange)及反射最大增益（Gmax)减小。（2）预先i.c.v.H1受体拮抗剂氯苯吡胺（CHL,5μg）或H2受体拮抗剂西咪替丁（CIM,15μg）,可明显减弱HA的上述效应,CIM的这种减弱作用不如CHL的显著。（3）预先同时i.c.v.CHL和CIM（分别为5和15μg）,能完全取消HA的效应。（4）预先向孤束核（NTS）内注射CHL（0.5μg）或CIM（1.5μg）,对HA效应的影响与i.c.v.CHL或CIM后的相类似,但NTS内注射CHL或CIM后i.c.v.HA所致的TP变化表现明显下降。以上结果提示,侧脑室给HA使CSR产生快速重调定,反射敏感性下降,功能受抑;其机制是通过中枢HA受体介导,H1受体的作用比H2受体更为明显;下丘脑-NTS的HA能通路可能是HA调节CSR的下行通路之一。NTS处的HA受体在i.c.v.HA抑制CSR的机制中可能发挥重要的作用。     

Effect of high local temperature on reflex cutaneous vasodilation

We examined the effect of high local forearm skin temperature (Tloc) on reflex cutaneous vasodilator responses to elevated whole-body skin (Tsk) and internal temperatures. One forearm was locally warmed to 42 degrees C while the other was left at ambient conditions to determine if a high Tloc could attenuate or abolish reflex vasodilation. Forearm blood flow (FBF) was monitored in both arms, increases being indicative of increases in skin blood flow (SkBF). In one protocol, Tsk was raised to 39-40 degrees C 30 min after Tloc in one arm had been raised to 42 degrees C. In a second protocol, Tsk and Tloc were elevated simultaneously. In protocol 1, the locally warmed arm showed little or no change in blood flow in response to increasing Tsk and esophageal temperature (average rise = 0.76 +/- 1.18 ml X 100 ml-1 X min-1), whereas FBF in the normothermic arm rose by an average of 8.84 +/- 3.85 ml X 100 ml-1 X min-1. In protocol 2, FBF in the normothermic arm converged with that in the warmed arm in three of four cases but did not surpass it. We conclude that local warming to 42 degrees C for 35-55 min prevents reflex forearm cutaneous vasodilator responses to whole-body heat stress. The data strongly suggest that this attenuation is via reduction or abolition of basal tone in the cutaneous arteriolar smooth muscle and that at a Tloc of 42 degrees C a maximum forearm SkBF has been achieved. Implicit in this conclusion is that local warming has been applied for a duration sufficient to achieve a plateau in FBF.     

Respiratory reflex responses to stimulation of tracheal mucosa in enflurane-anesthetized humans

We investigated respiratory reflex responses to tracheal mucosa stimulation induced by injection of distilled water in 13 female patients under three different depths of enflurane anesthesia (0.7, 1.0, and 1.3 minimum alveolar concentration). Detailed analysis of the types of reflex responses revealed that there are at least six different responses: 1) the apneic reflex, 2) the expiration reflex, 3) spasmodic, panting breathing, 4) the cough reflex, 5) slowing of breathing, and 6) rapid, shallow breathing. Among these reflex responses, the cough reflex was the most sensitive and the apneic reflex followed by slowing of breathing was the most resistant to deepening anesthesia, whereas the sensitivity of other types of reflex responses was in between. Our results indicate that the types of respiratory reflex responses to tracheal mucosa stimulation are associated with depths of anesthesia and that the differences in sensitivity to anesthesia may be a valuable sign in clinical assessment of depth of anesthesia.     

Inflammation enhances reflex and spinal neuron responses to noxious visceral stimulation in rats

To improve understanding of sensory processes related to visceral inflammation, the effect of turpentine-induced inflammation on reflex (cardiovascular/visceromotor) and extracellularly recorded lumbosacral dorsal horn neuron responses to colorectal distension (CRD) was investigated. A 25% solution of turpentine, applied to the colorectal mucosa, produced inflammation, decreased compliance of the colonic wall, and enhanced reflex responses in unanesthetized rats within 2-6 h. At 24 h posttreatment, pressor responses to CRD (80 mmHg, 20 s) were 20% greater, and intraluminal pressures needed to evoke visceromotor reflexes were 30% lower than controls. Parallel electrophysiological experiments in spinal cord-transected, decerebrate rats demonstrated that two neuronal subgroups excited by CRD were differentially affected by turpentine administered 24 h before testing. During CRD, abrupt neurons were 70% less active and sustained neurons were 25% more active than similar neurons in controls. In summary, reflex and neuronal subgroup (sustained neurons) responses to CRD were both potentiated by chemical inflammation. This suggests that the neurophysiological basis for inflammation-induced increases in reflex responses to CRD is increased activity of this neuronal subgroup.