Activation of both renin-angiotensin system (RAS) and the sympathetic system is the primary etiologic event in developing cardiovascular complications in diabetes mellitus (DM). However, the precise mechanisms for sympathetic activation in DM have not been elucidated. Here we attempted to investigate diabetes-linked cardiovascular dysregulation due to angiotensin II (Ang II)-mediated reduction in neuronal nitric oxide (NO) synthase (nNOS) within the paraventricular neuleus (PVN). In the present study, we used Ins2Akita (a spontaneous, insulin-dependent genetic diabetic non-obese murine model) and wild-type (WT) littermates mice as controls. At 14 weeks of age, we found the Akita mice had increased renal sympathetic nerve activity and elevated levels of plasma norepinephrine. There was decreased expression of nNOS protein (Akita 0.43 ± 0.11 vs. WT 0.75 ± 0.05, P < 0.05) in the PVN of Akita mice. Akita mice had increased expression of angiotensin-converting enzyme (ACE) (Akita 0.58 ± 0.05 vs. WT 0.34 ± 0.04, P < 0.05) and Ang II type 1 receptor (Akita 0.49 ± 0.03 vs. WT 0.29 ± 0.09, P < 0.05), decreased expressions of ACE2 (Akita 0.17 ± 0.05 vs. WT 0.27 ± 0.03, P < 0.05) and angiotensin (1-7) Mas receptor (Akita 0.46 ± 0.02 vs. WT 0.77 ± 0.07, P < 0.05). Futher, there were increased protein levels of protein inhibitor of nNOS (PIN) (Akita 1.75 ± 0.08 vs. WT 0.71 ± 0.09, P < 0.05) with concomitantly decreased catalytically active dimers of nNOS (Akita 0.11 ± 0.04 vs. WT 0.19 ± 0.02, P < 0.05) in the PVN in Akita mice. Our studies suggest that activation of the excitatory arm of RAS, leads to a decrease NO, causing an over-activation of the sympathetic drive in DM.
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http://dx.doi.org/10.1016/j.niox.2024.11.001 | DOI Listing |
Background: Senile dementia (SD) is a deteriorative organic brain disorder and it comprises Alzheimer's disease (AD) as a major variant. SD is shown impairment of mental capacities whereas AD is degeneration of neurons. According to World Health Organization (WHO) report; more than 55 million peoples have dementia and it is raising 10 million new cases every year.
View Article and Find Full Text PDFSheng Li Xue Bao
December 2024
College of Life Sciences, Fujian Normal University; Fujian Key Laboratory of Developmental and Neuro Biology, Fuzhou 350117, China.
Cancer pain is one of the most common symptoms in patients with advanced cancer. In this study, we aimed to investigate the effects of the -related gene C (MrgC) receptors on bone cancer pain. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured after the inoculation of Walker 256 mammary gland carcinoma cells into the tibia of adult Sprague-Dawley rats.
View Article and Find Full Text PDFAndrology
January 2025
Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey.
Background: Androgen deprivation is associated with erectile dysfunction (ED). In different animal models, sulfur dioxide (SO) donors NaSO and NaHSO reduced oxidative stress, fibrosis, and inflammation which contribute to the pathogenesis of androgen deprivation-induced ED, however the effect of SO donors on ED in castrated rats were not known.
Objective: To investigate the therapeutic effect of SO donors, NaSO/NaHSO, on ED in castrated rat model.
J Vet Res
December 2024
Institute of Biology, College of Natural Sciences, University of Rzeszów, 35-310 Rzeszów, Poland.
Introduction: The enteric nervous system (ENS) in the wall of the gastrointestinal tract is complex and comprises many neurons, which are differentiated in terms of structure, function and neurochemistry. Neuregulin 1 (NRG 1) is one of the neuronal factors synthesised in the ENS about the distribution and functions of which relatively little is known. The present study is the first description of the distribution of NRG 1 in the ENS in various segments of the porcine small intestine.
View Article and Find Full Text PDFNeuromolecular Med
January 2025
Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Chronic kidney disease (CKD) is a conceivable new risk factor for cognitive disorder and dementia. Uremic toxicity, oxidative stress, and peripheral-central inflammation have been considered important mediators of CKD-induced nervous disorders. Nitric oxide (NO) is a retrograde neurotransmitter in synapses, and has vital roles in intracellular signaling in neurons.
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