Renal actions of endothelin: interaction with prostacyclin

Chou, Shyan–Yih; Dahhan, Ali; Porush, Jerome G.

doi:10.1152/ajprenal.1990.259.4.f645

Cited by 21 publications

(14 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…29 In low dosage, intravenous bolus injections of endothelin can also decrease systemic and RVR in anesthetized cats. 30 Vasodilation results mainly from release of EDRF caused by ET-1, which would explain the decreased TPR that we observed in both DS and DR rats; release of prostacyclin (PGI2) 31 and ANP 32 may possibly contribute to a vasodilatory response to ET-1.…”

Section: Figure 3 Bar Graphs Show Effect Of Vasodilators (Atrial Natmentioning

confidence: 85%

Impaired renal vascular reactivity in prehypertensive Dahl salt-sensitive rats.

et al. 1992

View full text Add to dashboard Cite

We have previously shown that renal vascular resistance is less in Dahl salt-sensitive rats than salt-resistant rats fed 1% NaCI diets; however, renal vascular resistance increases before nonrenal vascular resistance as salt-sensitive rats develop hypertension when fed 8% NaCI diets. When saltresistant rats are given 8% NaCI diets, renal vascular resistance decreases. The current study reports effects of atrial natriuretic peptide, nitroprusside, norepinephrine, angiotensin II, and endothelin-1 on renal and nonrenal vascular resistance in prehypertensive salt-sensitive and salt-resistant rats given 1% NaCI diets; doses used did not affect blood pressure. Resistance of nonrenal vessels in salt-sensitive and salt-resistant rats responded similarly to dilators or constrictors. However, atrial natriuretic peptide and nitroprusside decreased renal vascular resistance of salt-resistant rats (by 65%, p< 0.01) but not that of salt-sensitive rats. Noreplnephrine, angiotensin H, and endothelin-1 increased renal vascular resistance in salt-sensitive rats by 126%, 135%, and 135%, respectively (p<0.01); norepinephrine and angiotensin II did not change renal vascular resistance of salt-resistant rats, but endothelin-1 decreased renal vascular resistance in salt-resistant rats by 30% (p<0.01). Reactivity of nonrenal blood vessels in prehypertensive salt-sensitive and salt-resistant rats was similar when infused with dilators or constrictors in doses used. By contrast, renal vessels of salt-sensitive rats did not dilate in response to atrial natriuretic peptide and nitroprusside but were hypersensitive to norepinephrine and angiotensin II. Endothelin-1 caused renal vasoconstriction in salt-sensitive rats and renal vasodilation in salt-resistant rats. Inappropriate renal vascular reactivity in prehypertensive salt-sensitive rats may play an important role in salt-induced hypertension. (Hypertension 1992^20:524-532) KEY WORDS • cardiac output • microspheres • renal circulation • vascular resistance • hypertension, sodium-dependent • rats, inbred strains T here is compelling evidence indicating an important role for the kidney and salt (NaCI) in the genesis of hypertension 1 ; however, the precise mechanism whereby salt elevates blood pressure remains unknown. The strain of salt-sensitive (DS) and salt-resistant (DR) rats developed by Dahl and coworkers 2 has been especially useful as an animal model for studying experimental hypertension. Some evidence implicates humoral factors, 34 neurogenic mechanisms, 5 and a deficient natriuretic capacity of the kidney 6 " 8 as possible causes of salt-induced hypertension in DS rats.Studies by Dahl et al 9 demonstrated that transplanting kidneys from DR rats into DS rats prevented salt-induced hypertension, whereas transplanting kidneys from DS rats into DR rats permitted salt-induced hypertension. From these results, they concluded that genetically determined characteristics of DS kidneys were responsible for salt sensitivity and the develop- Tobian et al, 8 Roman, 6 and Roman and Osborn 7 ...

show abstract

Section: Figure 3 Bar Graphs Show Effect Of Vasodilators (Atrial Natmentioning

confidence: 85%

Impaired renal vascular reactivity in prehypertensive Dahl salt-sensitive rats.

et al. 1992

View full text Add to dashboard Cite

show abstract

“…In animal models the vasoconstrictor peptide endothelin-1 stimulates the production of both vasodilatory and vasoconstrictor prostanoids, 18 -20 whereas the vasodilators prostacyclin (PGI2) and PGE2 inhibit ET-1 production. 21 In cultured endothelial cells, PGE2 and PGI2 cause an Ϸ40% inhibition of basal ET-1 secretion and a 50% inhibition of serum-stimulated ET-1 secretion in a dose-related and time course fashion by possibly stimulating particulate guanylate cyclase. 22 There is one study showing an effect of prostacyclin on endothelin in patients with PPH so far.…”

Section: Discussionmentioning

confidence: 97%

Influence of Inhaled Iloprost on Transpulmonary Gradient of Big Endothelin in Patients With Pulmonary Hypertension

et al. 2003

View full text Add to dashboard Cite

Background-The pulmonary circulation is an important site for the production and clearance of endothelin (ET)-1, a potent vasoactive and mitogenic peptide. In healthy individuals, 40% to 50% of circulating ET-1 is removed on each passage through the lungs resulting in an arteriovenous ratio of Ͻ1, whereas many patients with pulmonary arterial hypertension (PAH) have ratios Ͼ1, indicating reduced clearance or increased release of endothelin. The influence of inhaled prostanoids on endothelin clearance is unknown. Methods and Results-In a prospective investigation, plasma concentrations of big endothelin-1 (big ET-1, Elisa) were measured in 15 patients with pulmonary hypertension undergoing right heart catheterization with iloprost inhalation (4 m, 11 f, aged 35 to 75 years, mean pulmonary arterial pressure (PAPm) 54Ϯ2.3 mm Hg, pulmonary vascular resistance (PVR) 1061Ϯ141 dyn ϫ sec ϫ cm -5 ). There was a significant transpulmonary gradient for big ET-1 with 31% Ϯ11% higher concentrations in the radial artery than in the pulmonary artery (PϽ0.001). After inhalation of iloprost a significant decrease in the AV-ratio from 1.31Ϯ0.11 to 0.92Ϯ0.06 (PϽ0.007) was observed. The pulmonary net release of 3.10Ϯ0.65 pmol/min big ET-1 at baseline decreased to -1.24Ϯ1.32 pmol/min (Pϭ0.013) within 15 minutes indicating a restored balance. Patients under long-term treatment with iloprost (nϭ7) tended to have a lower net release and AV-ratio for big ET-1 than patients without pretreatment. Conclusion-An increase in pulmonary clearance of big-ET could be a mechanism contributing to the beneficial effects of inhaled prostanoids in the treatment of PAH.

show abstract

“…Endothelin is produced by, and binds to, most renal cell types [6]. ET-1 is known to cause a profound and prolonged renal vasoconstriction [7, 8]. ET-1 is also known to cause mesangial cell contraction [9, 10]and inhibition of sodium and water reabsorption by the nephron [11, 12, 13, 14], to enhance glomerular cell proliferation [15, 16], and to stimulate extracellular matrix accumulation [17].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of Endothelin A Receptor Sites in the Rabbit Diabetic Kidney: Potential Relevance to the Early Pathogenesis of Diabetic Nephropathy

Khan

Dashwood²,

Mumtaz³

et al. 1999

Nephron

View full text Add to dashboard Cite

Background/Aim: Nephropathy is an important complication of diabetes mellitus (DM). The plasma endothelin 1 (ET-1) levels are increased in DM, and ET-1 may cause deleterious effects on renal function. We, therefore, investigated whether changes in ET receptors occur in the DM rabbit kidney. Methods: Nine adult New Zealand White rabbits were injected with alloxan, of which 6 became diabetic; the other 3 acted as alloxan-treated controls. Six age-matched healthy rabbits served as controls. At 6 months, following cervical dislocation, the kidneys were removed, and sections (cortex and medulla) were incubated with ET_A and ET_B radioligands to produce low- and high-resolution autoradiographs. Immunohistochemical localization of ET-1 immunoreactivity was also performed. Results: There was greater ET_A and ET_B receptor binding in the control (ET_A p = 0.0003; ET_B p < 0.0001) and DM (ET_A p = 0.001; ET_B p < 0.0001) rabbits in the medulla as compared with the cortex. DM kidneys showed a significant increase in ET_A, but not ET_B, binding in the cortex (p < 0.0001) and in the medulla (p < 0.0001). High-resolution autoradiographs revealed striking [¹²⁵I]-ET-1 receptor binding predominantly to the glomeruli. Immunohistochemistry revealed dense ET-1 immunoreactivity associated with the renal tubules, but the glomeruli exhibited no staining. Alloxan-treated controls had similar results to age-matched controls. Conclusion: There are regional differences in both ET_A and ET_B binding in control and DM kidneys. ET_A receptor binding sites are increased in the DM kidney (cortex and medulla). ET-1 may act in a paracrine fashion on the glomeruli. These changes may contribute to the pathogenesis of diabetic nephropathy.

show abstract

Renal actions of endothelin: interaction with prostacyclin

Cited by 21 publications

References 0 publications

Impaired renal vascular reactivity in prehypertensive Dahl salt-sensitive rats.

Impaired renal vascular reactivity in prehypertensive Dahl salt-sensitive rats.

Influence of Inhaled Iloprost on Transpulmonary Gradient of Big Endothelin in Patients With Pulmonary Hypertension

Upregulation of Endothelin A Receptor Sites in the Rabbit Diabetic Kidney: Potential Relevance to the Early Pathogenesis of Diabetic Nephropathy

Contact Info

Product

Resources

About