Aims
Chronic increase of mineralocorticoids obtained by administration of deoxycorticosterone acetate (DOCA)
Conclusion
Overall, our study demonstrates that DOCA-salt requires an intact sympathetic drive to the spleen for priming of immunity and consequent BP increase. The coupling of nervous system and immune cells activation in the splenic marginal zone is established through a sympathetic-mediated PlGF release, suggesting that this pathway could be a valid therapeutic target for hypertension.
Results
To evaluate the role of the neurosplenic sympathetic drive in DOCA-salt hypertension, we challenged splenectomized mice or mice with left coeliac ganglionectomy with DOCA-salt, observing that they were both unable to increase BP. Then, we evaluated by immunofluorescence and ELISA levels of the placental growth factor (PlGF) upon DOCA-salt challenge, which significantly increased the growth factor expression, but only in the presence of an intact neurosplenic sympathetic drive. When PlGF KO mice were subjected to DOCA-salt, they were significantly protected from the increased BP observed in WT mice under same experimental conditions. In addition, absence of PlGF hampered DOCA-salt mediated T cells co-stimulation and their consequent deployment towards kidneys where they infiltrated tissue and provoked end-organ damage.