Perirenal adipose afferent nerves sustain pathological high blood pressure in rats

Abstract

Hypertension is a pathological condition of persistent high blood pressure (BP) of which the underlying neural mechanisms remain obscure. Here, we show that the afferent nerves in perirenal adipose tissue (PRAT) contribute to maintain pathological high BP, without affecting physiological BP. Bilateral PRAT ablation or denervation leads to a long-term reduction of high BP in spontaneous hypertensive rats (SHR), but has no effect on normal BP in control rats. Further, gain- and loss-of-function and neuron transcriptomics studies show that augmented activities and remodeling of L1-L2 dorsal root ganglia neurons are responsible for hypertension in SHR. Moreover, we went on to show that calcitonin gene-related peptide (CGRP) is a key endogenous suppressor of hypertension that is sequestered by pro-hypertensive PRAT in SHRs. Taken together, we identify PRAT afferent nerves as a pro-hypertensive node that sustains high BP via suppressing CGRP, thereby providing a therapeutic target to tackle primary hypertension.

Effect of focused power ultrasound-mediated perirenal fat modification on primary hypertension: protocol of a multicenter, randomized, double-blinded, sham-controlled study

“…Cumulating evidence showed that perirenal adipose tissue (PRAT) was significantly associated with high BP [ 7 – 9 ] Recently, it was revealed that perirenal adipose afferent nerves played a key role in sustaining pathological high BP in rats [ 10 ]. Long-term reduction of BP was observed in spontaneously hypertensive rats by bilateral PRAT ablation [ 10 ]. Thus, we hypothesize that the PRAT can be a potential target for lowing BP in clinical practice.…”

Effect of focused power ultrasound mediated perirenal fat modification on primary hypertension: protocol of a multicenter, randomized, double-blinded, sham-controlled study

“…However, observational studies failed to clari ed the pathological mechanism of hypertension caused by perirenal fat. Recently, researchers nd that bilateral perirenal fat ablation leads to a long-term reduction of high blood pressure in spontaneous hypertensive rats, and has no in uences on normal blood pressure in control rats, they further indicate that perirenal afferent nerves serve as a pathological node of hypertension that sustains elevated blood pressure via suppressing CGRP, thereby being a potential therapeutic target to tackle primary hypertension [10]. And the perirenal fat is so distinguished that no other fat pad such as inguinal, pararenal or epididymal adipose tissue, is associated with the maintenance of high blood pressure in their research.…”

“…Notably, perirenal fat is a unique connected tissue that is well vascularized and innervated [7]. Cumulating evidence showed that perirenal adipose tissue (PRAT) was signi cantly associated with high BP [7][8][9] Recently, it was revealed that perirenal adipose afferent nerves played a key role in sustaining pathological high BP in rats [10]. Long-term reduction of BP was observed in spontaneous hypertensive rats by bilateral PRAT ablation [10].…”

“…Cumulating evidence showed that perirenal adipose tissue (PRAT) was signi cantly associated with high BP [7][8][9] Recently, it was revealed that perirenal adipose afferent nerves played a key role in sustaining pathological high BP in rats [10]. Long-term reduction of BP was observed in spontaneous hypertensive rats by bilateral PRAT ablation [10]. Thus, we hypothesize that the PRAT can be a potential target for lowing BP in clinical practice.…”

Kidney-Protective Effects of SGLT2 Inhibitors

“…In addition, leptin production in the depot was decreased, a protein implicated in the development of glomerulosclerosis (59). Decreased leptin interaction with afferent nerves within perirenal fat may explain the decrease in kidney sympathetic nerve activity associated with SGLT2is (60,61). PPAR- δ , peroxisome proliferator–activated receptor- δ .…”