Early inflammatory response mediated by Angiotensin II in cardiac arteries of normotensive mice.

Oliveira, T. C. d. S.; Viegas, K. A. d. S.; Lima, R. S. d.; Campos, L. C. G.; Barauna, V. G.; Curi, R.; Irigoyen, M. C.; Lacchini, S.

doi:10.1101/2023.11.06.563831

bioRxiv · 10.1101/2023.11.06.563831

Early inflammatory response mediated by Angiotensin II in cardiac arteries of normotensive mice.

Oliveira, T. C. d. S.·Viegas, K. A. d. S.·Lima, R. S. d.·Campos, L. C. G.·Barauna, V. G.·Curi, R.·Irigoyen, M. C.·Lacchini, S.

View original source ↗Export metadata ↓

Abstract

To verify if a low dose of angiotensin II (Ang II) can induce an inflammatory response in cardiac arteries, even though blood pressure remains at normal values. Were used C57Bl/6J male mice treated with a low dose of Ang II (30ng/kg IP) and AT1R blockers. Blood pressure was recorded after 10, 30, 60min, 2 and 6hours after Saline or Ang II injection. Time curve (30 and 60min, 2, 6, 12, 24, and 48hours after treatment) for expression of inflammatory markers was evaluated in cardiac arteries (TGF-{beta}, IL-1{beta}, IL-6, TNF- and ICAM-1) by immunohistochemistry and western blot. Serum TNF- and IL-6 were analyzed by ELISA. Although Ang II did not alter blood pressure, local TGF- and IL-6 presented an early increase in cardiac arteries. IL-1{beta} and ICAM-1 participated in a late response to Ang II (12 hours). Ang II group showed a systemic increase of IL-6 30 to 60 minutes after treatment. AT1 and AT2 receptor blockers (losartan, 20mg/kg, and PD123.319, 15mg/kg) were given alone or concomitant to Ang II. This combination showed that Ang II increases TGF-{beta} and IL-6 by acting on the AT1 receptor in a fast response. IL-1{beta} regulation by Ang II seems to be mediated by both AT1 and AT2 receptors. The results suggest that, independently of hemodynamic influences, Ang II, acting on AT1R, leads to the expression of inflammatory markers in cardiac vessels. AT2 receptor seems to be involved in the counterbalance of AT1R during modulation of IL-1{beta} production in cardiac arteries.

Explore related subjects

physiology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Oliveira, T. C. d. S., Viegas, K. A. d. S., Lima, R. S. d., Campos, L. C. G., Barauna, V. G., Curi, R., Irigoyen, M. C., Lacchini, S.. 2023-11-07. Early inflammatory response mediated by Angiotensin II in cardiac arteries of normotensive mice.. https://doi.org/10.1101/2023.11.06.563831

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Thoracoabdominal pressure transmission during prone and supine cardiopulmonary resuscitation in fresh-frozen human cadavers

Background: Prone cardiopulmonary resuscitation (CPR) may be necessary when turning a prone patient supine would delay chest compressions. Although prone compressions can generate arterial pressures comparable with or greater than supine CPR, the pathway of pressure transmission is uncertain. We examined synchronized intrathoracic, intra-abdominal, and central arterial pressures in both supine and prone positions. Methods: Two thawed fresh-frozen adult cadavers underwent three, 2-minute mechanical CPR trials per position in a counterbalanced crossover sequence. Solid-state catheters recorded pleural, peritoneal, and central arterial pressures simultaneously. Trial-level outcomes included peak pressure, mean pressure, pressure-time area, and the mean peritoneal-to-pleural pressure gradient. Exploratory fixed-effects models included position, cadaver, and their interaction. Results: Prone CPR increased peak intrathoracic pressure by 7.04 mmHg, peak intra-abdominal pressure by 21.69 mmHg, and peak arterial pressure by 15.40 mmHg. Mean intra-abdominal and arterial pressures increased by 16.22 and 9.90 mmHg, respectively. The mean peritoneal-to-pleural gradient reversed direction from -8.46 mmHg supine to 4.85 mmHg prone. Intrathoracic pressure-time area increased 3.4-fold, from 1.62 to 5.46 mmHg{middle dot}s, and arterial pressure-time area increased 2.2-fold, from 2.96 to 6.42 mmHg{middle dot}s. Conclusions: Compared to supine, prone mechanical CPR generated higher arterial pressures and reversed the pressure relationship across the thoracoabdominal boundary in both cadavers. Higher abdominal pressure coincided with a larger intrathoracic pressure-time area, a pattern compatible with reduced caudal pressure dissipation.

physiology↗

bioRxiv2026

Hypothalamic Farnesoid X Receptor deficiency alters energy balance by modulating hepatic glucose production and adipose tissue metabolism through central insulin signaling.

Objectives: The bile acid nuclear receptor Farnesoid X Receptor (FXR, NR1H4) is a major regulator of metabolism and energy homeostasis in peripheral organs. It modulates bile acid, glucose, and lipid metabolism, as well as fat mass and body weight. However, FXR is also expressed in the brain, particularly in the hypothalamus, a key center for the regulation of energy homeostasis. Although one study has demonstrated a role for brain FXR activation in energy balance, its specific hypothalamic role is still unknown. Here, we examined the role of FXR in the mediobasal hypothalamus in the regulation of energy balance. Methods: We used a genetic approach combined with metabolic phenotyping to determine the effect of FXR invalidation in the mediobasal hypothalamus on metabolic parameters involved in the central regulation of energy homeostasis. Results: Our results demonstrate that hypothalamic FXR deficiency induces a positive energy balance, resulting in a reduction in energy expenditure due to alterations in glucose metabolism accompanied by structural changes in white adipose tissues. Conclusion: This study uncovers a previously unrecognized role for hypothalamic FXR in the central homeostatic control of energy balance, providing new insights into its contribution to peripheral glucose metabolism and adipose tissue structural remodeling.

physiology↗

bioRxiv2026

Rad and Phospholamban are Key Drivers of the Ventricular Adrenergic Response and Stress-Induced Arrhythmia

The adrenergic response is a fundamental mechanism that regulates heart rate (chronotropy), cardiac contractility (inotropy) and relaxation (lusitropy). Adrenergic stress is also a recognized trigger of arrhythmia in disease. Yet, our understanding of the underlying molecular basis remains incomplete. Protein kinase A (PKA) and the calcium/calmodulin-dependent kinase II (CaMKII) phosphorylate multiple targets proposed to participate in the adrenergic response, including the GTP-binding protein Rad, phospholamban (PLB) and ryanodine receptor 2 (RyR2). Here we demonstrate that phosphorylation of both Rad and PLB is necessary for inotropy and lusitropy. We show that changes in cardiac contractility and relaxation are primarily dependent on intracellular calcium handling. Finally, we report that Rad and PLB control stress-induced arrhythmogenesis, despite the phosphorylation of other pro-arrhythmic targets. We have identified the essential molecular components of the adrenergic response, resolving a long-standing debate in cardiac excitation-contraction coupling and refining current models of sympathetic regulation in health and disease.

physiology↗