The endothelium in health and disease - A target for therapeutic intervention

Chris R. Triggle, Morley Hollenberg, Todd J. Anderson, Hong Ding, Yan Fen Jiang, Lisa Ceroni, William B. Wiehler, S. S.M. Ng Ella, Anthie Ellis, Karen Andrews, John J. Mcguire, Malarvannan Pannirselvam

Research output: Contribution to journalArticle


In this review we discuss the contribution of NO, prostacyclin and endotheliumderived 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 endotheliumdependent vasodilatation results primarily from a decreased synthesis of endotheliumderived 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
Issue number3
Publication statusPublished - 1 Dec 1996



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

ASJC Scopus subject areas

  • Physiology

Cite this

Triggle, C. R., Hollenberg, M., Anderson, T. J., Ding, H., Jiang, Y. F., Ceroni, L., Wiehler, W. B., Ng Ella, S. S. M., Ellis, A., Andrews, K., Mcguire, J. J., & Pannirselvam, M. (1996). The endothelium in health and disease - A target for therapeutic intervention. Journal of Smooth Muscle Research, 32(3), 249-267.