title: Integration of renal sensory afferents at the level of the paraventricular nucleus dictating sympathetic outflow.
abstract: The sympathetic nervous system has been identified as a major contributor to the pathophysiology of chronic heart failure (CHF) and other diseases such as hypertension and diabetes, both in experimental animal models and patients. The kidneys have a dense afferent sensory innervation positioning it to be the origin of multimodal input to the central nervous system. Afferent renal nerve (ARN) signals are centrally integrated, and their activation results in a general increase in sympathetic tone, which is directed toward the kidneys as well as other peripheral organs innervated by the sympathetic nerves. In the central nervous system, stimulation of ARN increases the neuronal discharge frequency and neuronal activity in the paraventricular nucleus (PVN) of the hypothalamus. The activity of the neurons in the PVN is attenuated during iontophoretic application of glutamate receptor blocker, AP5. An enhanced afferent renal input to the PVN may be critically involved in dictating sympathoexcitation in CHF. Furthermore, renal denervation abrogates the enhanced neuronal activity within the PVN in rats with CHF, thereby possibly contributing to the reduction in sympathetic tone. Renal denervation also restores the decreased endogenous levels of neuronal nitric oxide synthase (nNOS) in the PVN of rats with CHF. Overall, these data demonstrate that sensory information originating in the kidney excites pre-autonomic sympathetic neurons within the PVN and this "renal-PVN afferent pathway" may contribute to elevated sympathetic nerve activity in hyper-sympathetic disease conditions such as CHF and hypertension.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, United States. Electronic address: kpatel@unmc.edu.
authors.forename: Kaushik P
authors.initials: KP
authors.lastname: Patel
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D006801:Humans; D007668:Kidney / Q000294:innervation* / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*
keywords: Afferent renal nerves; Cardiovascular; Paraventricular nucleus; Sympathetic activity