Perirenal Adipose Afferent Nerves Sustain Pathological High Blood Pressure

Hypertension is a pathological condition of persistent high blood pressure (BP) of which the underlying mechanisms remain largely obscure. Here, we show that the afferent nerves in perirenal adipose tissue are a regulatory site in triggering and maintaining pathological high BP, without affecting physiological BP. Bilateral perirenal adipose tissue (PRAT) ablation leads to a long-term and effective reduction of BP in spontaneous hypertensive rats (SHR) and high fat and high salt diet fed rats, but has no effect on normal BP in control Wistar-Kyoto or control SD rats. Moreover, gain- and loss-of-function studies show that augmented activities of L1-L2 dorsal root ganglia (DRG) neurons are responsible for hypertension in SHR. Further, L1-L2 DRG neuron transcriptomics uncovers significant changes in neuron development, remodeling, and plasticity. Importantly, calcitonin gene-related peptide (CGRP), a systemic vasodilator, is induced after PRAT ablation. We went on to show that CGRP antagonist blocks the BP-lowering effect of PRAT ablation. CGRP is therefore a key endogenous suppressor of hypertension that is sequestered by anti-hypertensive PRAT in SHRs. Taken together, we identify PRAT afferent nerves as a pathological node of hypertension that sustains high BP via suppressing CGRP, thereby providing a therapeutic target to tackle primary hypertension. Examination of mRNA profiles in DRG tissues from three PRATA spontaneously hypertensive rats and three sham-operated spontaneously hypertensive rats by Illumina RNA sequencing.