Capsaicin‐Induced Stimulation of Sensory Neurons in Adipose Tissue Promotes Increases in Blood Pressure in Mice Exposed to Early Life Stress

Abstract

Visceral adiposity has been largely implicated in increased sympathetic activation, and pathogenesis and target organ damage associated with the development of obesity‐induced hypertension. It has been shown that the experimental stimulation of afferent excitatory signals from adipose tissue contribute to increased sympathetic activation associated with obesity‐induced hypertension as part of a mechanism called the adipose afferent reflex (AAR). Previously, we have demonstrated that mice exposed to maternal separation and early weaning (MSEW) display increased sympathetic tone and mean arterial pressure (MAP) when fed high fat diet chronically. Thus, the aim of this study was to determine: 1) the contribution of subcutaneous white adipose tissue (scWAT) vs. gonadal WAT (gWAT) after acute capsaicin stimulation in MAP increases, and 2) the effect of MSEW on acute AAR response. Six‐months‐old control male C57BL/6 were implanted with carotid catheter for mean arterial pressure (MAP) measurements and subcutaneous or gonadal white adipose tissue were exposed for 0.9% saline and capsaicin injections (0.5 nmol/ul; 4 sites; 4ul/min; 2 min; bilateral; n=5). MAP did not change from baseline after saline injections in scWAT (79±2 vs. 78±3 mmHg, respectively; p=NS) nor after capsaicin injections in scWAT (75±3 vs. 76±3 mmHg, respectively; p=NS). In a different set of mice, saline injections in gWAT did not increase MAP from baseline (83±3 vs. 82±3 mmHg respectively; p=NS). However, MAP significantly increased from baseline during 10 minutes after capsaicin stimulation in gWAT (88±2 mmHg vs. 84±3 mmHg, respectively; p<0.05). Furthermore, MSEW mice showed a greater change in the capsaicin‐induced MAP increases compared to controls (delta MAP: 6±1 vs. 4±1 mmHg, p=0.053).After MAP responses, fat depots from control mice were removed to measure capsaicin‐induced calcitonin gene‐related peptide (CGRP) release in tissue explants (0, 0.1, 1, 10 uM capsaicin) by EIA bioassay. While capsaicin‐induced CGRP release from scWAT was increased in a dose‐dependent manner (143±33, 161±18, and 382±39 ng/mg tissue, p<0.05), in vitro gWAT stimulation did not induce any significant CGRP release at these doses.In additional studies, a different set of C57BL/6 mice were fed a high fat diet (60% kcal from fat, 16 weeks) and implanted with radiotelemeters to measure hemodynamic parameters at baseline and after gWAT chemical denervation with resiniferatoxin (RTX; 20 pmol/ul, 6 sites, 1 ul per site; bilateral). After 4 days, RTX sensory ablation decreased MAP (~3 mmHg) and HR (~50 bpm) in MSEW mice compared with controls.Thus, these results demonstrate that male mice show depot‐specific afferent signals that influence acute and chronic MAP control. In addition, mice exposed to MSEW seem to display a greater MAP response to capsaicin‐induced gWAT stimulation. These data suggest that AAR could play an important role in the exacerbated response to high fat diet‐induced increases in sympathetic tone and MAP observed in male MSEW mice.Support or Funding InformationR01HF135158 to ASL.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.