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 language | English |
|---|---|
| Pages (from-to) | 249-267 |
| Number of pages | 19 |
| Journal | Journal of Smooth Muscle Research |
| Volume | 39 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Dec 2003 |
| Externally published | Yes |
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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 journal › Review article
}
TY - JOUR
T1 - The Endothelium in Health and Disease - A Target for Therapeutic Intervention
AU - Triggle, Christopher
AU - Hollenberg, Morley
AU - Anderson, Todd J.
AU - Ding, Hong
AU - Jiang, Yanfen
AU - Ceroni, Lisa
AU - Wiehler, William B.
AU - Ng, Ella S M
AU - Ellis, Anthie
AU - Andrews, Karen
AU - McGuire, John J.
AU - Pannirselvam, Malarvannan
PY - 2003/12
Y1 - 2003/12
N2 - 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.
AB - 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.
KW - Diabetes
KW - EDHF
KW - Endothelial dysfunction
KW - Nitric oxide
KW - Potassium channels
UR - http://www.scopus.com/inward/record.url?scp=12144289742&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12144289742&partnerID=8YFLogxK
U2 - 10.1540/jsmr.39.249
DO - 10.1540/jsmr.39.249
M3 - Review article
VL - 39
SP - 249
EP - 267
JO - Journal of Smooth Muscle Research
JF - Journal of Smooth Muscle Research
SN - 0916-8737
IS - 6
ER -