Selective Activation of ETB Receptors Within the Paraventricular Nucleus Attenuates Hypertensive Cardiac Remodelling in DOCA-Salt Hypertensive Rats
Year: 2026
Type: article
Abstract: Hypertensive cardiac remodelling results from the interaction of hemodynamic overload, sympathetic dysregulation, and inflammation. The paraventricular nucleus (PVN) is a critical regulator of sympathetic outflow, but the contribution of PVN endothelin B (ETB) receptors to cardiac remodelling remains unknown. We investigated whether selective PVN ETB receptor activation protects against cardiac injury in DOCA-salt hypertension. Male Sprague-Dawley rats underwent DOCA-salt hypertension for five weeks and received chronic bilateral PVN infusion of the selective ETB receptor agonist BQ-3020 (52 ng/h) during the final 7 days. Blood pressure and heart rate were monitored longitudinally. Cardiac remodelling was evaluated by echocardiography, histology, immunofluorescence, Western blotting, and RT-qPCR. DOCA-salt hypertension increased PVN ETA and ETB receptor immunoreactivity and produced sustained hypertension, left ventricular hypertrophy, cardiomyocyte enlargement, myocardial fibrosis, and enhanced cardiac sympathetic remodelling, evidenced by increased TH, pTH/TH, and GAP-43. Myocardial TLR4/NF-κB signalling and TNF-α were increased, whereas IL-10 was reduced. PVN ETB receptor activation attenuated blood pressure elevation and markedly reduced hypertrophic, fibrotic, sympathetic remodelling, and inflammatory alterations. BQ-3020 also reduced heart rate AUC in both normotensive and hypertensive rats, without significant changes in the systolic function indices assessed. Selective activation of central ETB receptors attenuates hypertension and cardiac remodelling in DOCA-salt hypertensive rats. These findings support a role for PVN ETB signalling in the modulation of hypertensive cardiac remodelling, with changes in sympathetic remodelling markers suggesting a possible autonomic contribution.
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7225643379