Adrenergic neurotransmission increases in obesity‐associated hypertension

Abstract

Obesity‐related hypertension (HTN) is a risk factor for cardiovascular disease, stroke, type 2 diabetes, and kidney failure. Adrenergic neurotransmission is mediated by norepinephrine (NE) released from sympathetic nerve terminals onto effector tissues. Neuroeffector junctions on vascular smooth muscle in the mesenteric artery (MA) are an essential site whereby adrenergic neurotransmission regulates vascular tone, blood pressure, and blood flow distribution. The effect of obesity on adrenergic control of blood pressure in the MA is not well established, so our aim was to elucidate if and how adrenergic neurotransmission is altered during the development of obesity. We hypothesized that adrenergic‐mediated arterial constriction increases in obese male Dahl salt‐sensitive (Dahl SS) rats. Male Dahl SS rats were fed control diet (CD; 10% fat) or high‐fat diet (HFD; 60% fat) beginning at 3 weeks (wks) of age. Experiments were conducted after rats were fed for 10, 17, and 24 wks to establish a relationship between adrenergic neurotransmission and HTN development. Body weight (BW) was greater in HFD rats at all time points. Mean arterial pressure (MAP; measured by tail‐cuff) was greater in HFD rats at only 17 and 24 wks. Neurogenic constriction of MA was studied ex vivo using electrical field stimulation, a pressure myograph, and video imaging. Constriction response curves were left‐shifted in MA only from 24‐week HFD rats compared to 10‐ and 17‐week HFD rats. Constriction was similar between CD and HFD rats at all time points. MA reactivity to exogenous NE was decreased in the 24‐week CD and HFD rats compared to younger rats. There was no difference in MA reactivity between CD and HFD rats. Adrenergic nerve density was higher in HFD rats compared to CD rats at 10 and 24 wks. It also increased in a 24‐week CD and HFD rats compared to younger rats. TH (NE marker)‐immunoreactive nerve intensity was similar between CD and HFD rats at all time points. Plasma NE was increased at 24 wks in CD and HFD rats compared to 10 and 17‐week rats. However, plasma NE was similar between CD and HFD at all time points. Tissue NE content (measured by HPLC) was not different between CD and HFD rats, although decreased at the 24‐week CD and HFD rats compared to 10 and 17‐week rats. α2‐adrenergic autoreceptor and NE transporter functions were not altered by the HFD. We conclude that HTN in HFD‐induced obesity is partly mediated by overactivity of adrenergic nerves in a time‐dependent manner.Support or Funding InformationMichigan State UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.