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Aging and hypertension decrease endothelial NO-related dilating function and gamma-glutamyl transferase activity but

Caroline Perrin-Sarrado1, Fatima Dahboul1, Pierre Leroy1

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Aging and hypertension impair nitric oxide (NO) function and decrease vascular gamma-glutamyl transferase (GGT) activity. However, S-nitrosoglutathione (GSNO) may still offer therapeutic benefits for vascular protection.

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Area of Science:

  • Cardiovascular Physiology
  • Pharmacology
  • Biochemistry

Background:

  • Nitric oxide (NO) is crucial for vasodilation.
  • Aging and hypertension are associated with impaired NO-mediated vasodilation.
  • S-nitrosoglutathione (GSNO) is an NO donor requiring gamma-glutamyl transferase (GGT) for cellular NO transfer.

Purpose of the Study:

  • To investigate the impact of aging and hypertension on vascular GGT activity.
  • To assess the vasorelaxant effects of GSNO in aging and hypertensive rat models.
  • To determine if impaired NO-related vasodilation affects GSNO efficacy.

Main Methods:

  • Thoracic aortic rings from aged and adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were used.
  • Vasorelaxant responses to GSNO and carbachol were measured.
  • Vascular GGT activity was quantified using a chromogenic substrate.

Main Results:

  • Both aging and hypertension significantly reduced carbachol-induced vasodilation, indicating NO-related dilating dysfunction.
  • Aortic GGT activity decreased with aging and hypertension.
  • While NO-related vasodilation was impaired, the vasorelaxant response (pD2) to GSNO was not diminished in aged hypertensive rats.

Conclusions:

  • Aging and hypertension reduce NO-mediated vasodilation and vascular GGT activity.
  • Despite endothelial dysfunction, GSNO retains its vasorelaxant efficacy.
  • GSNO holds potential as a therapeutic agent to restore NO bioavailability and protect vasculature in conditions of endothelial dysfunction.