Xiaorui Tang

Baroreflex and chemoreflex controls of sympathetic activity following intermittent hypoxia

There is a large amount of evidence linking obstructive sleep apnea (OSA), and the associated intermittent hypoxia that accompanies it, with the development of hypertension. For example, cross-sectional studies demonstrate that the prevalence of hypertension increases with the severity of OSA (Bixler et al., 2000; Grote et al., 2001) and an initial determination of OSA is associated with a three-fold increase for future hypertension (Peppard et al., 2000). Interestingly, bouts of intermittent hypoxia have also been shown to affect sympathetic output associated with the baroreflex and chemoreflex, important mechanisms in the regulation of arterial blood pressure. As such, the possibility exists that changes in the baroreflex and chemoreflex may contribute to the development of chronic hypertension observed in OSA patients. The aim of the current article is to briefly review the response of the baroreflex and chemoreflex to intermittent hypoxic exposure and to evaluate evidence for the hypothesis that modification of these autonomic reflexes may, at least in part, support the comorbidity observed between chronic hypertension and OSA.

Pancreatic insulin and exocrine secretion are under the modulatory control of distinct subpopulations of vagal motoneurones in the rat

•  The pancreas consists of two functional parts, exocrine, which releases digestive enzymes, and endocrine, which releases hormones, such as insulin. •  Both parts are under neural regulatory control by the vagus nerve. Vago‐vagal neurocircuits integrate the sensory information, chemical or mechanical, from the gastrointestinal tract with the motor output back to the gastrointestinal system, including the pancreas. •  Both excitatory and inhibitory vago‐vagal neural circuits are regulated by many neurotransmitters, including glutamate acting on different types of metabotropic glutamate receptors. •  In this study, we show that different subtypes of metabotropic glutamate receptors regulate differentially exocrine and endocrine pancreatic functions by affecting different neurocircuits. •  The present study provides the physiological basis to develop pharmacological strategies aimed to provide a better understanding of pathophysiological conditions, such as pancreatitis or diabetes, that affect selectively the exocrine or endocrine pancreas.

The dmNTS is not the source of increased blood pressure variability in baroreflex denervated rats

A consistent and prominent feature, observed across many species, including our neuromuscular blocked (NMB) rat preparation, is that obliterating the baroafferent inputs to the brainstem, e.g., by sinoaortic denervation (SAD), significantly increases blood pressure variability (BPV). The sources of the BPV, however, are not completely understood, but involve both the central and the peripheral mechanisms. The key central noise source is likely in the brainstem. Previously, in NMB rats, we showed that the maximum gain of the baroreflex system is in the very low frequency (VLF) range of 0.01-0.2 Hz. In this study, using the same NMB preparation, we demonstrated that, after SAD, there was a significant increase in the VLF power of the expiratory systolic blood pressure (EsBP) spectrum, but a decrease in the VLF power of the expiratory heart inter-beat-interval (EIBI) spectrum. Because dmNTS is the only major common anatomic node for the vascular sympathetic and the cardiac parasympathetic pathways, the opposite changes in the post-SAD VLF powers of the EsBP and EIBI spectra suggest that dmNTS is unlikely the major noise source for the post-SAD BPV. Supporting this finding, we found that the dmNTS evoked response to single pulse baroreflex afferent aortic depressor nerve (ADN) stimuli was substantially more reliable than the evoked systolic blood pressure responses to the same stimuli.

Baroreflexes of the rat. VI. Sleep and responses to aortic nerve stimulation in the dmNTS

The sensitivity of the baroreflex determines its stability and effectiveness in controlling blood pressure (BP). Sleep and arousal are reported to affect baroreflex sensitivity, but the findings are not consistent across studies. After statistically correcting the effect of sleep on the baselines in chronically neuromuscular-blocked (NMB) rats, we found that sleep affects BP and heart period (HP) baroreflex gain similarly. This finding is consistent with baroreflex modulation of HP and BP before divergence of the sympathetic and parasympathetic pathways. Therefore, we hypothesized that the gain modulation occurs in the dorsal medial nucleus of the solitary tract (dmNTS). The present study used long-term dmNTS recordings in NMB rats and single-pulse aortic depressor nerve stimulation. Under these conditions, the magnitude of A-fiber evoked responses (ERs), recorded from second- or higher-order dmNTS baroreflex neurons, was reliably augmented during high-amplitude low-frequency EEG activity (slow-wave sleep) and reduced during low-amplitude high-frequency EEG activity (arousal; DeltaER = 11%, t = 9.49, P < 0.001, degrees of freedom = 1,016). This result has methodological implications for techniques that use changes in HP to estimate baroreflex BP gain and general implications for understanding the relationship between sleep and cardiovascular control.

Neural control of arterial pressure variability in the neuromuscularly blocked rat

The baroreflexes stabilize moment-to-moment arterial pressure. Sinoaortic denervation (SAD) of the baroreflexes results in a large increase in arterial pressure variability (APV) across various species. Due to an incomplete understanding of the nonlinear interactions between central and peripheral systems, the major source of APV remains controversial. While some studies suggested that the variability is endogenous to the central nervous system (CNS), others argued that peripheral influences may be the main source. For decades, abnormal cardiovascular variability has been associated with a number of cardiovascular diseases including hypertension, heart failure, and stroke. Delineating mechanisms of the APV is critical for the improvement of current strategies that use APV as a clinical tool for the diagnosis and prognosis of cardiovascular diseases. In this study, with a unique chronic neuromuscularly blocked (NMB) rat preparation that largely constrains peripheral influences, we determined the CNS contribution to the post-SAD APV. First, we confirmed that SAD significantly increased APV in the NMB rat, then demonstrated that post-SAD ganglionic blockade substantially reduced APV, and subsequent intravenous infusions of phenylephrine and epinephrine (in presence of ganglionic blockade) only slightly increased APV. These data suggest that the CNS is an important source, and skeletal activity, thermal challenges or other forms of peripherally generated cardiovascular stress are not required for the post-SAD APV. In addition, we showed that bilateral aortic denervation produced a larger increase in APV than bilateral carotid sinus denervation, suggesting that the aortic baroreflex plays a more dominant role in the control of APV than the carotid sinus.

Absence of Neuropathology With Prolonged Isoflurane Sedation in Healthy Adult Rats.

Background: The use of isoflurane sedation for prolonged periods in the critical care environment is increasing. However, isoflurane-mediated neurotoxicity has been widely reported. The goal of the present study was to determine whether long-term exposure to low-dose isoflurane in mechanically ventilated rodents is associated with evidence of neurodegeneration or neuroinflammation. Methods: Adult female Sprague-Dawley rats were used in this study. Experimental animals (n=11) were induced with 1.5% isoflurane, intubated, and given a neuromuscular blockade with &agr;-cobratoxin. EEG electrodes were surgically implanted, subcutaneous precordial EKG Ag wire electrodes, and bladder, femoral artery, and femoral vein cannulas permanently placed. After these procedures, the isoflurane concentration was reduced to 0.5% and, in conjunction with the neuromuscular blockade, continued for 7 days. Arterial blood gases and chemistry were measured at 3 time points and core body temperature servoregulated and maintenance IV fluids were given during the 7 days. Experimental animals and untreated controls (n=9) were euthanized on day 7. Results: Immunohistochemical and cytochemical assays did not detect evidence of microgliosis, astrocytosis, neuronal apoptosis or necrosis, amyloidosis, or phosphorylated-tau accumulation. Blood glucose levels were significantly reduced on days 3/4 and 6/7 and partial pressure of oxygen was significantly reduced, but still within the normal range, on day 6/7. All other blood measurements were unchanged. Conclusions: No neuropathologic changes consistent with neurotoxicity were detected in the brain after 1 week of continuous exposure to 0.5% isoflurane in healthy rats. These data suggest that even long exposures to low concentrations of isoflurane have no overt consequences on neuropathology.