Heterogeneous effect of aging on vasorelaxation responses in large and small arteries

Physiol Rep. 2020 Jan;8(1):e14341. doi: 10.14814/phy2.14341.

Abstract

Aging is associated with impaired vascular function characterized in part by attenuated vasorelaxation to acetylcholine (ACh) and sodium nitroprusside (SNP). Due to structural and functional differences between conduit and resistance arteries, the effect of aging on vasorelaxation responses may vary along the arterial tree. Our purpose was to determine age-related differences in vasorelaxation responses in large and small arteries. Responses to the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were assessed in abdominal aorta (AA), iliac arteries (IA), femoral arteries (FA), and gastrocnemius feed arteries (GFA) from young and old male rats. ACh-mediated vasorelaxation was significantly impaired in old AA and IA. SNP-mediated vasorelaxation was impaired in old AA. To investigate a potential mechanism for impaired relaxation responses in AA and IA, we assessed eNOS protein content and interactions with caveolin-1 (Cav-1), and calmodulin (CaM) via immunoprecipitation and immunoblot analysis. We found no age differences in eNOS content or interactions with Cav1 and CaM. Combined data from all rats revealed that eNOS content was higher in IA compared to AA and FA (p < .001), and was higher in GFA than AA (p < .05). Cav1:eNOS interaction was greater in FA than in AA and IA (p < .01), and in GFA compared to IA (p < .05). No differences in CaM:eNOS were detected. In conclusion, age-related impairment of vasorelaxation responses occurred in the large conduit, but not small conduit or resistance arteries. These detrimental effects of age were not associated with changes in eNOS or its interactions with Cav-1 or CaM.

Keywords: acetylcholine; calmodulin; caveolin-1; endothelial nitric oxide synthase; sodium nitroprusside.

Publication types

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

MeSH terms

  • Acetylcholine / pharmacology
  • Aging / metabolism
  • Aging / physiology*
  • Animals
  • Aorta, Abdominal / drug effects
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / physiopathology*
  • Arteries / drug effects
  • Arteries / metabolism
  • Arteries / physiopathology
  • Calmodulin / metabolism
  • Caveolin 1 / metabolism
  • Femoral Artery / drug effects
  • Femoral Artery / metabolism
  • Femoral Artery / physiopathology*
  • Iliac Artery / drug effects
  • Iliac Artery / metabolism
  • Iliac Artery / physiopathology*
  • Male
  • Muscle, Skeletal / blood supply
  • Nitric Oxide Synthase Type III / metabolism
  • Nitroprusside / pharmacology
  • Rats
  • Vasodilation / drug effects
  • Vasodilation / physiology*
  • Vasodilator Agents / pharmacology*

Substances

  • Calmodulin
  • Cav1 protein, rat
  • Caveolin 1
  • Vasodilator Agents
  • Nitroprusside
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Acetylcholine