Transient Increase in Sympathetic Constriction of Mesenteric Arteries from High Fat Diet‐Fed Dahl Salt‐sensitive Female Rats

Abstract

Obesity (BMI ≥ 30) is a risk factor for hypertension. Obesity‐associated hypertension is a risk factor for cardiovascular disease, stroke, type 2 diabetes and kidney failure. Hypertension is less common in premenopausal women compared to age‐matched men. This disparity fades away after the onset of menopause. Increased sympathoexcitation in the neuroeffector junction leads to increase in constriction of blood vessels. Differences in the mechanism/s neurogenic arterial constriction in male and female are not well understood. We hypothesized that sympathetic nerve activity in high fat diet‐induced hypertension is greater in male than female rat mesenteric arteries (MA). Rats were fed either control (C) or high fat (HF) diet beginning at 3 weeks of age, and used at 10, 17 and 24 weeks on diet. Body weight and systolic blood pressure (SBP) were measured weekly. HF males gained more weight than HF females at all time points. SBP was higher in HF rats compared to C rats in both sexes and across all time points. The estrus cycle stage was determined cytologically by vaginal lavage prior to euthanasia. Mesenteric arteries (Inner diameter; male=275–350 μm, female=245–315 μm) were harvested and mounted in a pressure (60 mmHg) myograph and inner diameter was measured continuously. MA contractile responses to electrical field stimulation (30 stimuli at 0.2–30 Hz) and drug applications were measured. Neurogenic constriction of MA from HF females was greater than HF males at 5 and 10 Hz at 10 wks, and at 5–30 Hz at 17 wks. At 24 wks the difference disappears. Constrictions caused by norepinephrine (NE) and ATP were similar in MA from HF male and female rats. Immunostaining for tyrosine hydroxylase (sympathetic nerve marker) and vesicular nucleotide transporter (ATP marker) revealed greater sympathetic nerve intensity in HF male than female rats at 10 and 24 wks. There was also greater intensity in MA from HF males than HF females at 10 and 17 wks. Moreover, HF males have higher NE and ATP nerve density than HF females at 10 and 17 but not for ATP at 24 wks. MA NE levels were similar in male and female rats. Prejunctional α2‐AR and NE transporter functions were not impaired in MA from HF Dahl salt‐sensitive rats. Taken together, despite sex differences in sympathetic nerve density in MA, we detected only transient sex differences in sympathetic neurogenic arterial constrictions. Contrary to our hypothesis, we found that HF females transiently have an upregulation of neurogenic sympathetic activity and this warrants further investigation into the mechanism.Support or Funding InformationResearch supported by PPG NIH Grant P01HL070687This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.