Premium
Sex Differences in Sympathetic Neuronal Control of Mesenteric Arteries from Obese Dahl SS Hypertensive Rats
Author(s) -
Gebremedhin Kibrom,
Galligan James,
Xu Hui
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1011.6
Subject(s) - medicine , endocrinology , constriction , myograph , mesenteric arteries , vasodilation , blood pressure , vasoconstriction , sympathetic nervous system , norepinephrine , mean arterial pressure , artery , heart rate , dopamine
Obesity‐associated hypertension is a risk factor for stroke, type 2 diabetes and kidney failure. Hypertension is less common in premenopausal women than in age‐matched men possibly due estrogen induced vasodilation in women. Sympathetic nerve activity increases in obesity‐related hypertension via the elevated norepinephrine (NE) and ATP release and increased constriction in resistance mesenteric arteries (MA). We hypothesized that the causes of obesity‐related hypertension differ between male and female Dahl salt‐sensitive (ss) rats. Rats were fed control and high fat (HF) diet beginning at 3 weeks of age. Body weight and mean arterial pressure (MAP) were measured until they were sacrificed at 24–26 weeks. Males (450 g) gained more weight than females (300 g) irrespective of diet and all HF fed rats became hypertensive (MAP>140 mmHg). The estrus cycle stage in female rats was determined cytologically by vaginal lavage before euthanasia. Mesenteric arteries (Inner diameter; male=275–350 μm, female=245–315 μm) were harvested and mounted on a pressure (60 mmHg) myograph and inner diameter was measured continuously. MA contractile responses to electrical field stimulation (30 stimuli at 0.2–30Hz) and drug applications were measured. MA neurogenic constriction was greater in HF‐fed male (n=9) compared to HF‐fed female arteries (n=3). Neurogenic constriction was similar in control animals while HF‐fed males had greater constriction than females. Neurogenic constriction did not vary with the estrus cycle in female rats regardless of diet. Neurogenic constrictions were blocked by combined application of prazosin (0.1 μM, α1‐adrenergic receptor antagonist) and PPADS (10 μM, P2X‐purinergic receptor antagonist) as well as suramin (100μM, P2X and P2Y‐purinergic receptor antagonist) in arteries from male and female rats. PPADS/Suramin inhibited ATP‐induced MA contraction. Constrictions caused by exogenous NE and ATP were similar in MA from HF‐fed male and female rats. Immunostaining for tyrosine hydroxylase (NE marker) and vesicular nucleotide transporter (ATP marker) revealed greater nerve distribution in HF‐fed MA from male and female rats. NE HPLC shows similar levels in male and female MA; however females have greater NE level in the perivascular fat. Our data indicate that the mechanisms of neurogenic vasoconstriction differ in MA from obese male and female rats. Differences in neurotransmission and/or nerve fiber distribution in obese male and in female rats might explain the sex differences in hypertension prevalence between human males and females. Support or Funding Information NIH PPG: P01HL070687