Endothelin contributes differently to peripheral vascular tone and blood pressure in human obesity and diabetes

Yoon, Nancy M.; Lteif, Amale; Han, Kyung-Ah; Mather, Kieren J.

doi:10.1016/j.jash.2007.10.006

Cited by 3 publications

(4 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This allows isolated assessment of the contribution of obesity per se to vascular and metabolic dysfunction, without confounding effects of contributions from other metabolic conditions. In prior studies in our lab where such vascular and metabolic dysfunction has been evident (1,2,42,43,57) this has provided an advantage in interpreting the findings. In the current study, however, we did not see baseline defects in adenosine‐stimulated vasodilation in obese subjects.…”

Section: Discussionmentioning

confidence: 99%

“…The 1 µmol/min exposure revealed significantly different peripheral vascular responses between lean and obese subjects. We have therefore used this infusion rate with other studies of systemic as well as limb exposures (1,42,43), and this rate was applied under the current protocol. Due to a recognized slow turnover of the pool of available ET A receptors, a prolonged exposure to the antagonist is required for full action (1,44,45).…”

Section: Methods and Proceduresmentioning

confidence: 99%

See 1 more Smart Citation

Role of Endogenous ET‐1 in the Regulation of Myocardial Blood Flow in Lean and Obese Humans

Mather

Lteif

Veeneman

et al. 2010

Obesity

Self Cite

View full text Add to dashboard Cite

Endothelin is an important determinant of peripheral vascular tone, and increased endogenous endothelin activity contributes to peripheral vascular dysfunction in human obesity. The contributions of endothelin to the regulation of coronary vascular tone in health in humans have not been well studied. We hypothesized that the contribution of endothelin to the regulation of myocardial perfusion would be augmented in human obesity. Using [NH3]ammonia positron emission tomography (PET), we measured myocardial perfusion under resting and adenosine‐stimulated conditions on two separate days, with and without concurrent exposure to BQ123, an antagonist of type A endothelin receptors (1 µmol/min IV beginning 90 min before measurement). We studied 10 lean and 9 obese subjects without hypertension, hyperlipidemia, or diabetes mellitus. We observed a BQ123‐induced increase in resting myocardial perfusion of ∼40%, not different between lean and obese subjects (BQ123‐induced increase in flow: lean 0.12 ± 0.20, obese 0.32 ± 0.51 ml/g/min, P = 0.02 BQ123 effect, P = 0.27 comparing response across groups). Although basal flow rates varied by region of the myocardium, the BQ123 effect was seen in all regions. BMI and cholesterol were significantly related to BQ123‐induced increases in basal tone in multivariable analysis. There was no baseline difference in the adenosine‐stimulated increase in blood flow between lean and obese subjects, and BQ123 failed to augment these responses in either group. These observations suggest that endothelin is an important contributor to the regulation of myocardial perfusion under resting conditions in healthy lean and obese humans, with increased contributions in proportion to increasing obesity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methods and Proceduresmentioning

confidence: 99%

Role of Endogenous ET‐1 in the Regulation of Myocardial Blood Flow in Lean and Obese Humans

Mather

Lteif

Veeneman

et al. 2010

Obesity

Self Cite

View full text Add to dashboard Cite

show abstract

“…Subjects with elevated body mass index (BMI) (both overweight and obese) present a chronic metabolic disorder with a distinct detriment of their cardiovascular health along with increased morbidity and mortality [ 226 , 227 ]. Characterised by an increased BP and an incidence of hypertension [ 228 ], this threat may result from endocrine and paracrine dysregulation and chronic inflammatory state that derive from irregularities in adipose tissue function [ 229 ]. This consequently elicits an instability amidst the NO pathway and ET-1 system resulting from a disruption in vascular homeostasis [ 229 ].…”

Section: Et-1 Association With Adverse Health Effects Related To Abnormal Body Weightmentioning

confidence: 99%

“…Yoon et al performed a study with obese patients, observing increased peripheral vasodilation in this group when compared to lean subjects. This revealed endothelin as a potent vasoconstrictor affecting vascular tone and diastolic blood pressure [ 228 ]. Another study investigated the relationship between elevated ET-1 activity in hypertensive subjects and increased body index.…”

Section: Et-1 Association With Adverse Health Effects Related To Abnormal Body Weightmentioning

confidence: 99%

Endothelin-1 axes in the framework of predictive, preventive and personalised (3P) medicine

et al. 2021

View full text Add to dashboard Cite

Endothelin-1 (ET-1) is involved in the regulation of a myriad of processes highly relevant for physical and mental well-being; female and male health; in the modulation of senses, pain, stress reactions and drug sensitivity as well as healing processes, amongst others. Shifted ET-1 homeostasis may influence and predict the development and progression of suboptimal health conditions, metabolic impairments with cascading complications, ageing and related pathologies, cardiovascular diseases, neurodegenerative pathologies, aggressive malignancies, modulating, therefore, individual outcomes of both non-communicable and infectious diseases such as COVID-19. This article provides an in-depth analysis of the involvement of ET-1 and related regulatory pathways in physiological and pathophysiological processes and estimates its capacity as a predictor of ageing and related pathologies, a sensor of lifestyle quality and progression of suboptimal health conditions to diseases for their targeted prevention and as a potent target for cost-effective treatments tailored to the person.

show abstract

Endothelial dysfunction and vascular disease - a 30th anniversary update

Vanhoutte¹,

et al. 2016

View full text Add to dashboard Cite

The endothelium can evoke relaxations of the underlying vascular smooth muscle, by releasing vasodilator substances. The best-characterized endothelium-derived relaxing factor (EDRF) is nitric oxide (NO) which activates soluble guanylyl cyclase in the vascular smooth muscle cells, with the production of cyclic guanosine monophosphate (cGMP) initiating relaxation. The endothelial cells also evoke hyperpolarization of the cell membrane of vascular smooth muscle (endothelium-dependent hyperpolarizations, EDH-mediated responses). As regards the latter, hydrogen peroxide (H O ) now appears to play a dominant role. Endothelium-dependent relaxations involve both pertussis toxin-sensitive G (e.g. responses to α -adrenergic agonists, serotonin, and thrombin) and pertussis toxin-insensitive G (e.g. adenosine diphosphate and bradykinin) coupling proteins. New stimulators (e.g. insulin, adiponectin) of the release of EDRFs have emerged. In recent years, evidence has also accumulated, confirming that the release of NO by the endothelial cell can chronically be upregulated (e.g. by oestrogens, exercise and dietary factors) and downregulated (e.g. oxidative stress, smoking, pollution and oxidized low-density lipoproteins) and that it is reduced with ageing and in the course of vascular disease (e.g. diabetes and hypertension). Arteries covered with regenerated endothelium (e.g. following angioplasty) selectively lose the pertussis toxin-sensitive pathway for NO release which favours vasospasm, thrombosis, penetration of macrophages, cellular growth and the inflammatory reaction leading to atherosclerosis. In addition to the release of NO (and EDH, in particular those due to H O ), endothelial cells also can evoke contraction of the underlying vascular smooth muscle cells by releasing endothelium-derived contracting factors. Recent evidence confirms that most endothelium-dependent acute increases in contractile force are due to the formation of vasoconstrictor prostanoids (endoperoxides and prostacyclin) which activate TP receptors of the vascular smooth muscle cells and that prostacyclin plays a key role in such responses. Endothelium-dependent contractions are exacerbated when the production of nitric oxide is impaired (e.g. by oxidative stress, ageing, spontaneous hypertension and diabetes). They contribute to the blunting of endothelium-dependent vasodilatations in aged subjects and essential hypertensive and diabetic patients. In addition, recent data confirm that the release of endothelin-1 can contribute to endothelial dysfunction and that the peptide appears to be an important contributor to vascular dysfunction. Finally, it has become clear that nitric oxide itself, under certain conditions (e.g. hypoxia), can cause biased activation of soluble guanylyl cyclase leading to the production of cyclic inosine monophosphate (cIMP) rather than cGMP and hence causes contraction rather than relaxation of the underlying vascular smooth muscle.

show abstract

Endothelin contributes differently to peripheral vascular tone and blood pressure in human obesity and diabetes

Cited by 3 publications

References 47 publications

Role of Endogenous ET‐1 in the Regulation of Myocardial Blood Flow in Lean and Obese Humans

Role of Endogenous ET‐1 in the Regulation of Myocardial Blood Flow in Lean and Obese Humans

Endothelin-1 axes in the framework of predictive, preventive and personalised (3P) medicine

Endothelial dysfunction and vascular disease - a 30th anniversary update

Contact Info

Product

Resources

About