Disease relevance of EDN1

• Filarial dogs, which commonly develop serious pulmonary hypertension, exhibited by far the highest ET-1 levels of the disease states examined [1].
• Elevated endothelin-1 expression in dogs with heartworm disease [1].
• Endothelin (ET) is a potent vasoconstrictor peptide which is elevated in plasma in congestive heart failure [2].
• BACKGROUND: Plasma levels of endothelin-1 (ET-1) increase during ischemia and could potentially contribute to impairment of myocardial blood flow (MBF) [3].
• This suggests that endothelin-1 plays a role in the pathophysiology of hypertension but contributes to a lesser extent to the maintenance of normal blood pressure [4].

High impact information on EDN1

• Angiotensin converting enzyme inhibition modulates endogenous endothelin in chronic canine thoracic inferior vena caval constriction [2].
• These results indicate that endothelin is a potent vasoconstrictor that elevates systemic blood pressure in association with marked decreases in cardiovascular and renal function [5].
• Intravenous infusion of endothelin (50 ng/kg per min) increases arterial pressure by increasing peripheral vascular resistance but in association with an increase in coronary vascular resistance and decreases in cardiac output [5].
• Endothelin, a newly discovered endothelial-derived peptide, has been demonstrated in vitro to have potent vasocontractile properties and has been speculated to play a role in vivo in arterial pressure-volume homeostasis [5].
• Administration of phenylephrine to the myocytes increased endothelin-1 levels in the supernatant, but only to subthreshold concentrations [6].

Chemical compound and disease context of EDN1

• ET-1 receptor antagonism by bosentan lowers blood pressure in hypertension [7].
• Hepatoprotective effect of the endothelin receptor antagonist TAK-044 against ischemia-reperfusion injury in the canine liver [8].
• Efficacy of administering an endothelin-receptor antagonist (SB209670) in ameliorating ischemia-reperfusion injury in lung allografts [9].
• Neither group showed any change in body weight, fasting plasma glucose, atrial natriuretic factor, or endothelin-1 levels [10].
• Angiotensin II and endothelin-1 receptor antagonists have cumulative hypotensive effects in canine Page hypertension [11].

Biological context of EDN1

• Based on the fact that ET-1 is a potent bioactive mediator that induces vasoconstriction and promotes vascular remodeling, these findings suggest that ET-1 plays an important role in the pathophysiology of dog dirofilariasis as an aggravating factor by inducing pulmonary hypertension [1].
• Endothelin (ET)-1 is involved in the pathophysiology of various renal disorders, promoting renal cellular proliferation and extracellular matrix protein accumulation, and, thus, diminishing fundamental renal function, including filtration [12].
• BACKGROUND: Cyclosporin A is reported to impair endothelium-mediated vasorelaxation and induce endothelin release in some noncoronary vascular beds [13].
• Coronary endothelial production of prostacyclin in response to increasing concentrations of ET-1 represents an important means of blunting the vasoconstrictor properties of ET-1 in the canine coronary circulation [3].
• Moreover, within the group with experimental CHF, right atrial pressure and pulmonary capillary wedge pressure correlated independently with circulating endothelin levels [14].

Anatomical context of EDN1

• METHODS AND RESULTS: ET-1 (group 1, n = 5) or sarafotoxin, a specific ET-B receptor agonist (group 3, n = 6) (each at 2 ng/kg per minute), was infused into the left circumflex coronary artery in the anesthetized dog [15].
• The endothelium possesses the ability to modulate vascular tone by the release of vasodilators and vasoconstrictors, among them endothelium-derived relaxing factor (EDRF) and endothelin (ET) [16].
• CONCLUSIONS: Blood flow to normal myocardium is increased at moderate plasma elevations of ET-1, whereas collateral blood flow is unchanged [3].
• Surprisingly, endothelin-induced increases of Ca2+ were not different in smooth muscle of collateral and noncollateral arteries (P > .05) [17].
• CONCLUSIONS: Cardiac myocytes have a requisite role in constriction of coronary resistance vessels to alpha1-adrenergic stimuli, which may be mediated by endothelin-1 and other unidentified myocyte-derived vasoconstrictors [6].

Associations of EDN1 with chemical compounds

• We conclude that the hemodynamic and hormonal adaptation after xenon plus remifentanil and isoflurane plus remifentanil anesthesia does not depend on the endothelin system, because it is unaffected by ET(A) receptor inhibition [18].
• BACKGROUND: Mature coronary collateral arteries are hyperresponsive to vasopressin; in contrast, contractile responses of collaterals to endothelin are attenuated [17].
• In the present study, we examined the effects of intravenous bosentan, a nonpeptide, competitive endothelin-1 receptor antagonist, on hemodynamics in dogs with chronic heart failure [19].
• Coronary collateral vessels demonstrate a much greater dependence on prostacyclin production in blunting the vasoconstrictor properties of ET-1 [3].
• After indomethacin administration, ET-1 (10 ng/min) caused a 120 +/- 23% increase in collateral vascular resistance (P < .05) and abolished the vasodilation that this dose produced in the normal zone [3].

Regulatory relationships of EDN1

• Cardiotrophin-1 stimulates endothelin-1 via gp130 in vascular endothelial cells [20].
• The selective endothelin-A-receptor antagonist LU 135.252 inhibits the direct arrhythmogenic action of endothelin-1 [21].
• Endothelin-1 promotes vascular structural remodeling during the progression of heart failure prevention of vascular remodeling using a specific endothelin-converting enzyme inhibitor [22].
• The renal prostacyclin synthesis was augmented by endothelin without stimulating the renal renin release or norepinephrine output [23].

Other interactions of EDN1

• PURPOSE: Experiments were designed to determine whether angiotensin converting enzyme inhibition with quinaprilat can prevent endothelin-mediated decreases in renal blood flow and the glomerular filtration rate in the anesthetized dog [24].
• Endothelin at pathophysiological concentrations mediates coronary vasoconstriction via the endothelin-A receptor [15].
• This study was designed to investigate the changes in plasma and tissue endothelin-1/endothelin-2 (ET) after liver ischemia and to assess the protective effect of anti-ET 1/ET 2 monoclonal antibody (ET antibody) against ischemia-reperfusion injury [25].
• Endothelin-1 infusion also produced an inhibitory effect on renin release [26].
• Stimulation of the renin-angiotensin system by endothelin subtype A receptor blockade in conscious dogs [27].

Analytical, diagnostic and therapeutic context of EDN1

• MBF was measured with radioactive microspheres at baseline and during 30-minute infusions of ET-1 (1, 10, and 100 ng/min) into the left main coronary artery [3].
• Accordingly, the role of endothelin was assessed using the nonpeptidyl, dual ETA/ETB endothelin antagonist L-754,142 in a model of renal insufficiency in the anesthetized dog induced by cross-clamping the suprarenal aorta for 60 min, followed by 2 h of reperfusion [28].
• During electrical stimulation (1 Hz, 9 V, 2 msec), the contractions to endothelin-1 were reduced significantly [29].
• We conclude that treatment of lung allografts with the mixed endothelin A/endothelin B (ETA/ETB) receptor antagonist SB209670 can ameliorate ischemia-reperfusion injury, resulting in improved graft function and survival after lung transplantation [9].
• Arterial and venous plasma ET-1 concentrations increased after transplantation; however, they were significantly higher in the treatment group [9].

References