Inflammation of some visceral sensory systems and autonomic dysfunction in cardiovascular disease.

The sensitization and hypertonicity of visceral afferents are highly relevant to the development and progression of cardiovascular and respiratory disease states. In this review, we described the evidence that the inflammatory process regulates visceral afferent sensitivity and tonicity, affecting the control of the cardiovascular and respiratory system. Some inflammatory mediators like nitric oxide, angiotensin II, endothelin-1, and arginine vasopressin may inhibit baroreceptor afferents and contribute to the baroreflex impairment observed in cardiovascular diseases. Cytokines may act directly on peripheral afferent terminals that transmit information to the central nervous system (CNS). TLR-4 receptors, which recognize lipopolysaccharide, were identified in the nodose and petrosal ganglion and have been implicated in disrupting the blood-brain barrier, which can potentiate the inflammatory process. For example, cytokines may cross the blood-brain barrier to access the CNS. Additionally, pro-inflammatory cytokines such as IL-1ß, IL-6, TNF-α and some of their receptors have been identified in the nodose ganglion and carotid body. These pro-inflammatory cytokines also sensitize the dorsal root ganglion or are released in the nucleus of the solitary tract. In cardiovascular disease, pro-inflammatory mediators increase in the brain, heart, vessels, and plasma and may act locally or systemically to activate/sensitize afferent nervous terminals. Recent evidence demonstrated that the carotid body chemoreceptor cells might sense systemic pro-inflammatory molecules, supporting the novel proposal that the carotid body is part of the afferent pathway in the central anti-inflammatory reflexes. The exact mechanisms of how pro-inflammatory mediators affects visceral afferent signals and contribute to the pathophysiology of cardiovascular diseases awaits future research.

Baroreceptor and chemoreceptor contributions to the hypertensive response to bilateral carotid occlusion in conscious mice.

This study aimed to characterize the role played by baroreceptors and chemoreceptors in the hypertensive response to bilateral carotid occlusion (BCO) in conscious C57BL mice. On the day before the experiments the animals were implanted with pneumatic cuffs around their common carotid arteries and a femoral catheter for measurement of arterial pressure. Under the same surgical approach, groups of mice were submitted to aortic or carotid sinus denervation or sham surgery. BCO was performed for 30 or 60 s, promoting prompt and sustained increase in mean arterial pressure and fall in heart rate. Compared with intact mice, the hypertensive response to 30 s of BCO was enhanced in aortic-denervated mice (52 ± 4 vs. 41 ± 4 mmHg; P < 0.05) but attenuated in carotid sinus-denervated mice (15 ± 3 vs. 41 ± 4 mmHg; P < 0.05). Suppression of peripheral chemoreceptor activity by hyperoxia [arterial partial pressure of oxygen (Pa(O(2))) > 500 mmHg] attenuated the hypertensive response to BCO in intact mice (30 ± 6 vs. 51 ± 5 mmHg in normoxia; P < 0.05) and abolished the bradycardia. It did not affect the hypertensive response in carotid sinus-denervated mice (20 ± 4 vs. 18 ± 3 mmHg in normoxia; P < 0.05). The attenuation of the hypertensive response to BCO by carotid sinus denervation or hyperoxia indicates that the hypertensive response in conscious mice is mediated by both baro- and chemoreceptors. In addition, aortic denervation potentiates the hypertensive response elicited by BCO in conscious mice.