Male and female high-fat diet-fed Dahl SS rats are largely protected from vascular dysfunctions: PVAT contributions reveal sex differences

Am J Physiol Heart Circ Physiol. 2021 Jul 1;321(1):H15-H28. doi: 10.1152/ajpheart.00131.2021. Epub 2021 Apr 30.


Vascular dysfunctions are observed in the arteries from hypertensive subjects. The establishment of the Dahl salt-sensitive (SS) male and female rat models to develop a reproducible hypertension with high-fat (HF) diet feeding from weaning allows addressing the question of whether HF diet-associated hypertension results in vascular dysfunction similar to that of essential hypertension in both sexes. We hypothesized that dysfunction of three distinct vascular layers, i.e., endothelial, smooth muscle, and perivascular adipose tissue (PVAT), would be present in the aorta from HF diet-fed versus control diet-fed male and female rats. Dahl SS rats were fed a control (10% kcal of fat) or HF (60%) diet from weaning for 24 wk. Male and female Dahl SS rats became equally hypertensive when placed on a HF diet. For male and female rats, the thoracic aorta exhibited medial hypertrophy in HF diet-induced hypertension versus control, but neither displayed a hyperresponsive contraction to the α-adrenergic agonist phenylephrine nor an endothelial cell dysfunction as measured by acetylcholine-induced relaxation. A beneficial PVAT function, support of stress relaxation, was reduced in the male versus female rats fed a HF diet. PVAT in the aorta of males but not in females retained the anticontractile activity. We conclude that this HF model does not display the same vascular dysfunctions observed in essential hypertension. Moreover, both male and female show significantly different vascular dysfunctions in this HF feeding model.NEW & NOTEWORTHY Although the aorta exhibits medial hypertrophy in response to HF diet-induced hypertension, it did not exhibit hyperresponsive contraction to an α-adrenergic agonist nor endothelial cell dysfunction; this was true for both sexes. Unlike other hypertension models, PVAT around aorta from (male) rats on the HF diet retained significant anticontractile activity. PVAT around aorta of the male on a HF diet was modestly more fibrotic and lost the ability to assist in arterial stress relaxation.

Keywords: Dahl SS; PVAT remodeling; endothelial dysfunction; hypertension; vascular hyperresponsiveness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology*
  • Diet, High-Fat*
  • Female
  • Male
  • Rats
  • Rats, Inbred Dahl
  • Sex Factors
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology
  • Vasodilation / drug effects
  • Vasodilation / physiology*


  • Acetylcholine