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Schoborg, Robert V., Donald B. Hoover, John D. Tompkins, and John C. Hancock. Increased ganglionic responses to substance P in hypertensive rats due to upregulation of [NK.sub.1] receptors. Am J Physiol Regulatory Integrative Comp Physiol 279: R1685-R1694, 2000.--Intravenous injection of substance P (SP) increases renal nerve firing and heart rate in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) by stimulating sympathetic ganglia. Blood pressure is increased in SHRs but lowered in WKYs. This study assesses the role of neurokinin-1 ([NK1.sub.1]) receptors in mediating the ganglion actions of SP. Rats for functional studies were anesthetized and then treated with chlorisondamine. Renal nerve, blood pressure, and heart rate responses to intravenous injection of the [NK.sub.1] receptor agonist GR-73632 were similar but less than those to equimolar doses of SP in SHRs. GR-73632 only slightly increased renal nerve firing and heart rate and lowered blood pressure in WKYs. The [NK.sub.1] receptor antagonist GR-82334 (200 nmol/kg iv) blocked the ganglionic actions of GR-73632 and the pressor response to SP in SHRs. It reduced the renal nerve and heart rate responses by 52 and 35%. This suggests that the pressor response to SP is mediated by ganglionic [NK.sub.1] receptors and that [NK.sub.1] receptors also have a prominent role in mediating the renal nerve and heart rate responses to SP. Quantitative autoradiography showed that [NK.sub.1] receptors are more abundant in the superior cervical ganglia of SHRs. RT-PCR showed increased abundance of [NK.sub.1] receptor mRNA in SHRs as well. These observations suggest that the greater ganglionic stimulation caused by SP in SHRs is due to upregulation of [NK.sub.1] receptors. neurokinin-1 receptors; hypertension; sympathetic nervous system; inbred spontaneously hypertensive rats

Focuses on a study which assessed the role of neurokinin-1 receptors in mediating the ganglion actions of substance P (SP) in rats. Details on SP; Materials and methods; Results of the study.

Altered gut microbial diversity has been associated with several chronic disease states, including heart failure. Stimulation of the vagus nerve, which innervates the heart and abdominal organs, is proving to be an effective therapeutic in heart failure. We hypothesized that cervical vagus nerve stimulation (VNS) could alter fecal flora and prevent aberrations observed in fecal samples from heart failure animals. To determine whether microbial abundances were altered by pressure overload (PO), leading to heart failure and VNS therapy, a VNS pulse generator was implanted with a stimulus lead on either the left or right vagus nerve before creation of PO by aortic constriction. Animals received intermittent, open-loop stimulation or sham treatment, and their heart function was monitored by echocardiography. Left ventricular end-systolic and diastolic volumes, as well as cardiac output, were impaired in PO animals compared with baseline. VNS mitigated these effects. Metagenetic analysis was then performed using 16S rRNA sequencing to identify bacterial genera present in fecal samples. The abundance of 10 genera was significantly altered by PO, 8 of which were mitigated in animals receiving either left- or right-sided VNS. Metatranscriptomics analyses indicate that the abundance of genera that express genes associated with ATP-binding cassette transport and amino sugar/nitrogen metabolism was significantly changed following PO. These gut flora changes were not observed in PO animals subjected to VNS. These data suggest that VNS prevents aberrant gut flora following PO, which could contribute to its beneficial effects in heart failure patients., (Copyright © 2016 the American Physiological Society.)