Angiotensin peptide synthesis and cyclic nucleotide modulation in sympathetic stellate ganglia

Abstract

Chronically elevated angiotensin II is a widely-established contributor to hypertension and heart failure via its action on the kidneys and vasculature. It also augments the activity of peripheral sympathetic nerves through activation of presynaptic angiotensin II receptors, thus contributing to sympathetic over-activity. Although some cells can synthesise angiotensin II locally, it is not known if this machinery is present in neurons closely coupled to the heart. Using a combination of RNA sequencing and quantitative real-time polymerase chain reaction, we demonstrate evidence for a renin-angiotensin synthesis pathway within human and rat sympathetic stellate ganglia, where significant alterations were observed in the spontaneously hypertensive rat stellate ganglia compared with Wistar stellates. We also used Förster Resonance Energy Transfer to demonstrate that administration of angiotensin II and angiotensin 1-7 peptides significantly elevate cyclic guanosine monophosphate in the rat stellate ganglia. Whether the release of angiotensin peptides from the sympathetic stellate ganglia alters neurotransmission and/or exacerbates cardiac dysfunction in states associated with sympathetic over activity remains to be established.

Human pluripotent stem cell-derived functional sympathetic neurons express ACE2 and RAAS components: a framework for studying the effect of COVID-19 on sympathetic responsiveness

“…Here, we propose an hPSC-based model of symNs that may be useful for studying SNS-associated effects of SARS-CoV-2 infection and could provide a platform for future drug testing and screening. Using this model, we confirmed previous reports [ 6 ] that ACE2/RAAS components are expressed in human symNs. We further showed that their electrical activity is sensitive to Ang II, ACE2 downregulation, and SARS-CoV-2 pseudovirus infection.…”

“…Sympathetic hyperactivation has been reported in the aging population and in people with pre-existing comorbidities such as chronic lung disease and hypertension, as well as in SARS-CoV-2 infected patients [ 1 ]. ACE2 and RAAS components have been detected in human and rodent stellate ganglia [ 6 ] and in human dorsal root ganglia [ 7 ]. However, to our knowledge, it has not yet been shown whether SARS-CoV-2 infects human symNs.…”

Efficacy of phentolamine combined with ambroxol aerosol inhalation in the treatment of pediatric severe pneumonia and its effect on serum IL-10 and CRP levels

“…Children are susceptible to pathogenic bacteria due to their low immunity and immature respiratory tract, which can trigger pneumonia (1,2). Pediatric pneumonia, a common respiratory disease with acute onset and rapid progression, often occurs in infants and young children due to genetic, environmental, nutritional, and other factors.…”

SARS-CoV-2 spike protein inhibits megalin-mediated albumin endocytosis in proximal tubule epithelial cells

“…Angiotensin II (Ang II) concentrations were determined by ELISA as previously published [25] , [26] . After treatment, the cell supernatants were harvested and clarified by centrifugation at 1000 ×g for 10 min to remove any cell debris.…”