The Endothelium in Health and Disease - A Target for Therapeutic Intervention

Christopher Triggle, Morley Hollenberg, Todd J. Anderson, Hong Ding, Yanfen Jiang, Lisa Ceroni, William B. Wiehler, Ella S M Ng, Anthie Ellis, Karen Andrews, John J. McGuire, Malarvannan Pannirselvam

Research output: Contribution to journalReview article

85 Citations (Scopus)

Abstract

In this review we discuss the contribution of NO, prostacyclin and endothelium-derived relaxing factor - endothelium-derived hyperpolarizing factor, or EDHF, to vascular function. We also explore the hypotheses (1): that tissues can store NO as nitrosothiols (RSNOs) and (2) that such RSNO stores can be modulated by physiological and pathophysiological processes. Notably in the microcirculation, EDHF appears to play an important role in the regulation of vascular tone. Leading candidates for EDHF include extracellular potassium (K+), an epoxygenase product, hydrogen peroxide and/or a contribution from myoendothelial gap junctions. Data from our laboratory indicate that in mouse vessels, different endothelium-dependent vasodilators, such as acetylcholine and protease-activated receptor (PAR) agonists, release different endothelium-derived relaxing factors. The combination of two K-channel toxins, apamin and charybdotoxin, inhibits EDHF activity in most protocols. Endothelial dysfunction is considered as the major risk factor and a very early indicator of cardiovascular disease including the cardiovascular complications of type I & types II diabetes. Impaired endothelium-dependent vasodilatation results primarily from a decreased synthesis of endothelium-derived nitric oxide (NO) and/or an increase in the production of reactive oxygen species such as superoxide. We have shown that the administration of tetrahydrobiopterin, an important co-factor for nitric oxide synthase (NOS) partially restores endothelial function (1) in leptin-deficient mice (db/db) with spontaneous type II diabetes, as well as (2) in human vascular tissue harvested for coronary artery bypass grafting (CABG). These data suggest that a deficiency in the availability of tetrahydrobiopterin plays an important role in vascular dysfunction associated with Type II diabetes. In addition, changes in the contribution of EDHF occur in vascular tissue from the db/db mice suggesting a compensatory increase in EDHF production; whether this alteration in EDHF production is physiological or pathophysiological remains controversial.

Original languageEnglish
Pages (from-to)249-267
Number of pages19
JournalJournal of Smooth Muscle Research
Volume39
Issue number6
DOIs
Publication statusPublished - Dec 2003
Externally publishedYes

Fingerprint

Endothelium
Blood Vessels
Endothelium-Dependent Relaxing Factors
Health
Nitric Oxide
Type 2 Diabetes Mellitus
Therapeutics
Proteinase-Activated Receptors
Physiological Phenomena
Charybdotoxin
Apamin
Gap Junctions
Epoprostenol
Microcirculation
Leptin
endothelium-dependent hyperpolarization factor
Vasodilation
Coronary Artery Bypass
Nitric Oxide Synthase
Superoxides

Keywords

  • Diabetes
  • EDHF
  • Endothelial dysfunction
  • Nitric oxide
  • Potassium channels

ASJC Scopus subject areas

  • Physiology

Cite this

The Endothelium in Health and Disease - A Target for Therapeutic Intervention. / Triggle, Christopher; Hollenberg, Morley; Anderson, Todd J.; Ding, Hong; Jiang, Yanfen; Ceroni, Lisa; Wiehler, William B.; Ng, Ella S M; Ellis, Anthie; Andrews, Karen; McGuire, John J.; Pannirselvam, Malarvannan.

In: Journal of Smooth Muscle Research, Vol. 39, No. 6, 12.2003, p. 249-267.

Research output: Contribution to journalReview article

Triggle, C, Hollenberg, M, Anderson, TJ, Ding, H, Jiang, Y, Ceroni, L, Wiehler, WB, Ng, ESM, Ellis, A, Andrews, K, McGuire, JJ & Pannirselvam, M 2003, 'The Endothelium in Health and Disease - A Target for Therapeutic Intervention', Journal of Smooth Muscle Research, vol. 39, no. 6, pp. 249-267. https://doi.org/10.1540/jsmr.39.249
Triggle, Christopher ; Hollenberg, Morley ; Anderson, Todd J. ; Ding, Hong ; Jiang, Yanfen ; Ceroni, Lisa ; Wiehler, William B. ; Ng, Ella S M ; Ellis, Anthie ; Andrews, Karen ; McGuire, John J. ; Pannirselvam, Malarvannan. / The Endothelium in Health and Disease - A Target for Therapeutic Intervention. In: Journal of Smooth Muscle Research. 2003 ; Vol. 39, No. 6. pp. 249-267.
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