ArticleCirculation research2012
Neurohormonal modulation of the innate immune system is proinflammatory in the prehypertensive spontaneously hypertensive rat, a genetic model of essential hypertension.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 107 citations in OpenAlex.
- Sex differences in TLR4 expression in SHR do not contribute to sex differences in blood pressure or the renal T cell profile.American journal of physiology. Regulatory, integrative and comparative physiology · 2022Trial
- Uncoupling Protein 2 and Nitric Oxide Deficiency Favor Glycolytic Pathways and Organ Growth in the Rat Spleen.Current issues in molecular biology · 2026Article
- Anti-hyperplastic effects of Acmella oleracea flower and leaf extracts in prostate cell lines and in spontaneously hypertensive rats.Journal of molecular histology · 2026Article
- The immune-microbiome axis in salt-sensitive hypertension: a focus on renal and neural mechanisms.Frontiers in physiology · 2025Review
- Immune Mechanisms in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Cholinergic Stimulation Exerts Cardioprotective Effects and Alleviates Renal Inflammatory Responses after Acute Myocardial Infarction in Spontaneous Hypertensive Rats (SHRs).Pharmaceuticals (Basel, Switzerland) · 2024Article
- Carotid Baroreceptor Stimulation Improves Pulmonary Arterial Remodeling and Right Ventricular Dysfunction in Pulmonary Arterial Hypertension.JACC. Basic to translational science · 2024Article
- Placental TLR recognition of salivary and subgingival microbiota is associated with pregnancy complications.Microbiome · 2024Article
- Dynamic dysregulation of transcriptomic networks in brainstem autonomic nuclei during hypertension development in the female spontaneously hypertensive rat.Physiological genomics · 2024Article
- Inflammation Resolution in the Cardiovascular System: Arterial Hypertension, Atherosclerosis, and Ischemic Heart Disease.Antioxidants & redox signaling · 2024Review
- Possible organ-protective effects of renal denervation: insights from basic studies.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Review
- Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease.Biomedicines · 2022Review
- Pathogenetic Mechanisms of Hypertension-Brain-Induced Complications: Focus on Molecular Mediators.International journal of molecular sciences · 2022Review
- Identification of biomarkers, pathways and potential therapeutic agents for salt-sensitive hypertension using RNA-seq.Frontiers in cardiovascular medicine · 2022Article
- Molecular biochemical aspects of salt (sodium chloride) in inflammation and immune response with reference to hypertension and type 2 diabetes mellitus.Lipids in health and disease · 2021Review
- Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats.Scientific reports · 2021Article
- Pathophysiology of Hypertension: The Mosaic Theory and Beyond.Circulation research · 2021Review
- Toll-Like Receptors in the Pathogenesis of Essential Hypertension. A Forthcoming Immune-Driven Theory in Full Effect.International journal of molecular sciences · 2021Review
- Immunity and Hypertension.Acta physiologica (Oxford, England) · 2021Review
- Nicotine Alleviates Cortical Neuronal Injury by Suppressing Neuroinflammation and Upregulating Neuronal PI3K-AKT Signaling in an Eclampsia-Like Seizure Model.Neurotoxicity research · 2020Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
rationaleInflammation and autonomic dysfunction contribute to the pathophysiology of hypertension. Cholinergic stimulation suppresses innate immune responses. Angiotensin II (Ang II) induces hypertension and is associated with proinflammatory immune responses.
objectiveOur goal was to define the innate immune response in a model of genetic hypertension and the influences of cholinergic stimulation and Ang II. METHODS AND
resultsStudies were conducted on 4- to 5-week-old prehypertensive spontaneously hypertensive rats (SHRs) and age-matched normotensive control, Wistar Kyoto (WKY) rats. Isolated splenocytes were preexposed to nicotine or Ang II before Toll-like receptor (TLR) activation. Culture supernatants were tested for cytokines (tumor necrosis factor-α, interleukin [IL]-10, and IL-6). TLR-mediated cytokine responses were most pronounced with TLR7/8 and TLR9 activation and similar between WKY rats and SHRs. Nicotine and Ang II enhanced this TLR-mediated IL-6 response in prehypertensive SHR splenocytes. In contrast, nicotine suppressed the TLR-mediated IL-6 response in WKY rats, whereas Ang II had no effect. In vivo, nicotine enhanced plasma levels of TLR7/8-mediated IL-6 and IL-1β responses in prehypertensive SHRs but suppressed these responses in WKY rats. Flow cytometry revealed an increase in a CD161+ innate immune cell population, which was enhanced by nicotine in the prehypertensive SHR spleen but not in WKY.
conclusionsThere is a pronounced anti-inflammatory nicotinic/cholinergic modulation of the innate immune system in WKY rats, which is reversed in prehypertensive SHRs. The results support the novel concept that neurohormonal regulation of the innate immune system plays a role in the pathogenesis of genetic hypertension and provide putative molecular targets for treatment of hypertension.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.