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Age-dependent decrease in endothelium-dependent hyperpolarizations to endothelin-3 in the rat mesenteric artery

M Nakashima1, P M Vanhoutte

  • 1Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas.

Journal of Cardiovascular Pharmacology
|January 1, 1993
PubMed
Summary
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Aging significantly reduces the endothelium-dependent hyperpolarizing effects of endothelin-3 (ET-3) and acetylcholine in rat mesenteric arteries. This age-related decline impacts vascular smooth muscle cell responses.

Area of Science:

  • Vascular Biology
  • Cardiovascular Physiology
  • Aging Research

Background:

  • Endothelium-derived hyperpolarizing factors (EDHFs) play a crucial role in regulating vascular tone.
  • Endothelin-3 (ET-3) is implicated in endothelium-dependent relaxations.
  • Age-related changes in vascular function are a significant concern in cardiovascular health.

Purpose of the Study:

  • To investigate the impact of aging on the endothelium-dependent hyperpolarizing effect of ET-3 in rat mesenteric arteries.
  • To compare the effects of ET-3 and acetylcholine on vascular smooth muscle cell membrane potential across different age groups.

Main Methods:

  • Superior mesenteric arteries from young, adult, and old Wistar-Kyoto rats were utilized.
  • Vascular smooth muscle cell membrane potential was measured using glass microelectrodes.

Related Experiment Videos

  • Experiments were conducted in the presence of indomethacin and NG-nitro-L-arginine (NLA) to isolate specific signaling pathways.

    • Main Results:

    • ET-3 induced concentration-dependent hyperpolarization in young rats, with diminished responses in adult and absent responses in old rats.
    • Acetylcholine also caused hyperpolarization, but its maximal amplitude was reduced in old rats.
    • Aging decreased endothelium-dependent hyperpolarizations evoked by both ET-3 and acetylcholine.

    Conclusions:

    • Aging significantly impairs endothelium-dependent hyperpolarization in rat mesenteric arteries.
    • The responsiveness to ET-3 is particularly sensitive to age-related vascular changes.
    • These findings highlight age-associated alterations in vascular smooth muscle cell signaling pathways.