Site specific regulation in the kidney of endothelin and its receptor subtypes by cyclosporine

Iwasaki, Shigeki; Homma, Teiichi; Kon, Valentina

doi:10.1038/ki.1994.77

Cited by 61 publications

(29 citation statements)

References 23 publications

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“…Furthermore, the dog basilar artery exhibited an increase in ETB receptor binding sites after experimental subarachnoid haemorrhage (Roux et al, 1995). Increased intracellular calcium due to ETB receptor activation has been seen in aortic smooth muscle cells from spontaneous hypertensive rats as compared with controls (Batra et al, 1993), and rat kidney medulla demonstrated an upregulation of the ETB receptor mRNA after treatment with cyclosporin (Iwasaki et al, 1994). These data together with the present study suggest that the ETA receptor is more static as compared to the ETB receptor, and consequently the regulation of the ETB receptor may have physiological or pathophysiological implications.…”

Section: Resultsmentioning

confidence: 99%

Plasticity of contractile endothelin‐B receptors in human arteries after organ culture

Adner

Cantera

Ehlert

et al. 1996

British J Pharmacology

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1 The pharmacology and mRNA expression of endothelin (ET) receptors in human omental arteries were characterized by use of functional contractile assays and the reverse transcriptase-polymerase chain reaction (RT-PCR). 2 In freshly obtained segments of human omental arteries, ET-1 and ET-3 induced concentrationdependent contractions which were normalized to the response produced by 60 mM K+. ET 4 Two-site analysis of the ET-1 induced concentration-response curve from cultured arteries suggests that ETB receptors, at the high potency component, and ETA receptors, at the low potency component, contribute both to the contractile response in relative proportion of 70% and 30%, respectively. Further analysis suggested that the ETA receptor would be capable of evoking at least 75% of the ET-1 contraction in the absence of ETB receptors, although with a lower potency as compared to fresh arteries.5 Electrophoresis of RT-PCR products from the smooth muscle layer of freshly obtained human arteries indicated the presence of mRNA for both ETA and ETB receptors. Arteries cultured for 1 and 5 days demonstrated an increase of mRNA for the ETB receptor as compared to the ETA receptor. The identities of the PCR products were verified by restriction enzyme digestion. 6 In freshly obtained human omental arteries, the contractile effects of endothelins appear to be mediated predominantly by the ETA receptor subtype, with a negligible contribution by ETB receptors. Cultured arterial segments, however, exhibited a substantial ETB receptor mediated contractile response and an increase in ETB receptor mRNA content, consistent with an upregulation of functional ETB receptors. These in vitro data suggest plasticity in the smooth muscle cell expression of contractile ETB receptors.

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Section: Resultsmentioning

confidence: 99%

Plasticity of contractile endothelin‐B receptors in human arteries after organ culture

Adner

Cantera

Ehlert

et al. 1996

British J Pharmacology

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“…Endothelin 1 (ET-1) concentrations are higher in cyclosporin-A-treated patients compared to controls with comparable renal function [61, 62]. The increment in plasma endothelin concentrations is dose-dependent.…”

Section: What Are the Mechanisms Leading To Hypertension In The Graftmentioning

confidence: 99%

Hypertension in the Transplanted Patient

Zeier

Mandelbaum

Ritz

1998

Nephron

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Hypertension is a common finding after renal transplantation, and it has a variety of underlying mechanisms. One reason is the type of immunosuppressive therapy, with a higher prevalence of hypertension in cyclosporine-treated patients. Cyclosporine interferes with several humoral and neural systems which are involved in blood pressure regulation such as the renin-angiotensin system, endothelins, nitric oxide, prostaglandins and the sympathetic nervous system. Other pathomechanisms for posttransplant hypertension are uncontrolled renin secretion of the native kidneys, polycythemia, recurrence of renal disease in the graft and renal failure. Renal transplant artery stenosis is a potentially treatable cause of post-transplant hypertension and several techniques such MRT angiography, Doppler sonography and conventional angiography are available. The diagnosis and treatment of hypertension are of high importance in general for the transplanted patient, and especially for the long-term prognosis of graft function.

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“…Quantification of ET-1, ECE-1, and CNP mRNAs was performed using the competitive polymerase chain reaction (PCR) method as previously reported. 21 The sequences of sense and antisense primers for ET-1, 22 CNP, 23 ECE-1, 24 and eNOS 25 were designed as previously reported. The intra-and interassay variabilities of the competitive PCR were 11.9% and 12.9%, respectively, for ET-1, 12.2% and 13.4% for CNP, 12.0% and 13.1% for ECE-1, and 12.3% and 13.9% for eNOS.…”

Section: Competitive Polymerase Chain Reaction For Et-1 Ece-1 and Cmentioning

confidence: 99%

Mechanisms of FK 506–Induced Hypertension in the Rat

et al. 1999

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Abstract-Tacrolimus (FK 506) is a powerful, widely used immunosuppressant. The clinical utility of FK 506 is complicated by substantial hypertension and nephrotoxicity. To clarify the mechanisms of FK 506 -induced hypertension, we studied the chronic effects of FK 506 on the synthesis of endothelin-1 (ET-1), the expression of mRNA of ET-1 and endothelin-converting enzyme-1 (ECE-1), the endothelial nitric oxide synthase (eNOS) activity, and the expression of mRNA of eNOS and C-type natriuretic peptide (CNP) in rat blood vessels. In addition, the effect of the specific endothelin type A receptor antagonist FR 139317 on FK 506 -induced hypertension in rats was studied. FK 506, 5 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 given for 4 weeks, elevated blood pressure from 102Ϯ13 to 152Ϯ15 mm Hg and increased the synthesis of ET-1 and the levels of ET-1 mRNA in the mesenteric artery (240% and 230%, respectively). Little change was observed in the expression of ECE-1 mRNA and CNP mRNA. FK 506 decreased eNOS activity and the levels of eNOS mRNA in the aorta (48% and 55%, respectively). The administration of FR 139317 (10 mg ⅐ kg Ϫ1 ⅐ d Ϫ1) prevented FK 506 -induced hypertension in rats. These results indicate that FK 506 may increase blood pressure not only by increasing ET-1 production but also by decreasing NO synthesis in the vasculature. 1,2 FK 506 is 10 to 100 times more potent than cyclosporin (CysA). 3 The nephrotoxic side effects of CysA and the development of hypertension observed during CysA treatment also seem to be characteristic side effects of FK 506. 4 The incidence of hypertension in previously normotensive liver or heart transplant recipients treated with CysA has been reported to be 80% to 90%.5 A lower incidence (50% to 70%) of hypertension in FK 506 -treated recipients has been reported. 6 Although renal dysfunction is usually also present in transplant recipients treated with CysA or FK 506, blood pressure elevations have been observed in the absence of detectable renal dysfunction. 7,8 The exact mechanism of FK 506 -induced hypertension is unclear, but several researchers have suggested that the primary pathogenic mechanism may be vascular. 9 We have reported that CysA and FK 506 both increased the synthesis of endothelin-1 (ET-1) in cultured vascular endothelial cells. 10The natriuretic peptides organize a family of 3 distinct peptides (atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], and C-type natriuretic peptide [CNP]) and are involved in body fluid homeostasis and blood pressure control. CNP is reported to be synthesized in the vascular endothelial cells and to possess local effects of vascular tone and remodeling.11 Nitric oxide (NO) is synthesized from L-arginine by 2 enzymes. The generation of NO by constitutive, Ca 2ϩ -dependent NO synthase (NOS) from the vascular endothelium plays an important role in the homeostasis of the vascular system. Three isoforms of NOS have been cloned from rat brain (nNOS), vascular endothelium (eNOS), and inducible Ca 2ϩ -independent enzyme (iNOS). Vascular eNOS mainta...

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Site specific regulation in the kidney of endothelin and its receptor subtypes by cyclosporine

Cited by 61 publications

References 23 publications

Plasticity of contractile endothelin‐B receptors in human arteries after organ culture

Plasticity of contractile endothelin‐B receptors in human arteries after organ culture

Hypertension in the Transplanted Patient

Mechanisms of FK 506–Induced Hypertension in the Rat

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