Marked reduction of mortality in salt-loaded Dahl salt- sensitive rats by the new, selective endothelin ETA receptor antagonist, J-105859

Okada, Megumu; Nishino, Masaya; Saito, Masanori; Ikeda, Takanori; Uehara, Sayuri; Okada, Hiromasa; Niiyama, Kenji; Ohtake, Norikazu; Hayama, Takashi; Nishikibe, Masaru

doi:10.1097/00004872-200018120-00016

Cited by 13 publications

(12 citation statements)

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“…The inbred SS strains of rodents that were generated for this research exhibited a specific pattern of target organ damage and increased mortality. [346][347][348][349][350][351][352][353][354][355][356] However, these experiments were conducted in animals that had developed established hypertension. Therefore, it was not possible to tease out the relative roles of SSBP and an elevated BP itself in determining organ damage or mortality.…”

Section: Prognostic Significance Of Ssbpmentioning

confidence: 99%

Salt Sensitivity of Blood Pressure

Elijovich¹,

Weinberger²,

Anderson³

et al. 2016

Hypertension

370

230

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The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on January 23, 2016, and the American Heart Association Executive Committee on February 23, 2016. A copy of the document is available at http://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@ wolterskluwer.com.The American Heart Association requests that this document be cited as follows: Elijovich F, Weinberger MH, Anderson CAM, Appel LJ, Bursztyn M, Cook NR, Dart RA, Newton-Cheh CH, Sacks FM, Laffer CL; on behalf of the American Heart Association Professional and Public Education Committee of the Council on Hypertension; Council on Functional Genomics and Translational Biology; and Stroke Council. Salt sensitivity of blood pressure: a scientific statement from the American Heart Association. Hypertension. 2016;68:e7-e46. doi: 10.1161/HYP.0000000000000047.Expert peer review of AHA Scientific Statements is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit http://professional.heart.org/statements. Select the "Guidelines & Statements" drop-down menu, then click "Publication Development."Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/CopyrightPermission-Guidelines_UCM_300404_Article.jsp. A link to the "Copyright Permissions Request Form" appears on the right side of the page. Figure 2 shows the major effect of aging in increasing the prevalence of SSBP in both normotensive and hypertensive subjects. An important and encouraging observation is that the multiple phenotypic characteristics described in pure SS strains of rodents reproduce those observed in humans, indicating that the phenotypic cluster of SSBP can be brought out in humans by the current techniques used in carefully controlled research. Additionally, despite the unquestionable influence of environmental factors in the determination of SSBP in humans, estimates of its heritability have been as high as 74% in blacks 9 and 50% in Chinese subjects, 10 both higher than those for hypertension. Salt Sensitivity of Blood PressureAn important issue is the clinical significance of the SSBP phenotype. There was increasing understanding that it represents an abnormality. The reasons w...

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Section: Prognostic Significance Of Ssbpmentioning

confidence: 99%

Salt Sensitivity of Blood Pressure

Elijovich¹,

Weinberger²,

Anderson³

et al. 2016

Hypertension

370

230

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show abstract

“…This time pattern indicates that in the Dahl S rats studied, the pressor effect of a H-Na diet did not precede the increase in CSF [Na ϩ ]. In other studies in 6-to 8-wk-old male Dahl S rats using telemetry, hypertension also did not develop until several days on high salt intake (14,33).…”

Section: Discussionmentioning

confidence: 75%

Increases in CSF [Na⁺] precede the increases in blood pressure in Dahl S rats and SHR on a high-salt diet

Huang¹,

Vliet²,

Leenen³

2004

American Journal of Physiology-Heart and Circulatory Physiology

130

145

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In Dahl salt-sensitive (S) and salt-resistant (R) rats, and spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, at 5-6 wk of age, a cannula was placed in the cisterna magna, and cerebrospinal fluid (CSF) was withdrawn continuously at 75 microl/12 h. CSF was collected as day- and nighttime samples from rats on a regular salt intake (0.6% Na+; R-Na) and then on a high salt intake (8% Na+; H-Na). In separate groups of rats, the abdominal aorta was cannulated and blood pressure (BP) and heart rate (HR) measured at 10 AM and 10 PM, with rats first on R-Na and then on H-Na. On H-Na, CSF [Na+] started to increase in the daytime of day 2 in Dahl S rats and of day 3 in SHR. BP and HR did not rise until day 3 in Dahl S rats and day 4 in SHR. In Dahl R and WKY rats, high salt did not change CSF [Na+], BP, or HR. In a third set of Dahl S rats, sampling of both CSF and BP was performed in each individual rat. Again, significant increases in CSF [Na+] were observed 1-2 days earlier than the increases in BP and HR. In a fourth set of Dahl S rats, BP and HR were recorded continuously by means of radiotelemetry for 5 days on R-Na and 8 days on H-Na. On H-Na, BP (but not HR) increased first in the nighttime of day 2. In another set of Dahl S rats, intracerebroventricular infusion of antibody Fab fragments binding ouabain-like compounds (OLC) with high affinity prevented the increase in BP and HR by H-Na but further increased CSF [Na+]. Finally, in Wistar rats on H-Na, intracerebroventricular infusion of ouabain increased BP and HR but decreased CSF [Na+]. Thus, in both Dahl S and SHR on H-Na, increases in CSF [Na+] preceded the increases in BP and HR, consistent with a primary role of increased CSF [Na+] in the salt-induced hypertension. An increase in brain OLC in response to the initial increase in CSF [Na+] appears to attenuate further increases in CSF [Na+] but at the "expense" of sympathoexcitation and hypertension.

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“…1], a new selective and potent endothelin ET A receptor antagonist (Okada et al, 2000), underwent significant acyl glucuronidation and acyl glucosidation in human liver microsomes. To determine the mechanism of both conjugations, we evaluated the kinetics of the glucuronide and glucoside formation and mutual inhibition of UDPGA and UDPG on conjugation reactions.…”

mentioning

confidence: 99%

Acyl Glucuronidation and Glucosidation of a New and Selective Endothelin ET_AReceptor Antagonist in Human Liver Microsomes

Tang¹,

Hochman²,

Ma³

et al. 2003

Drug Metab Dispos

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Marked reduction of mortality in salt-loaded Dahl salt- sensitive rats by the new, selective endothelin ETA receptor antagonist, J-105859

Abstract: J-105859 is a selective, potent, orally active ETA-selective antagonist ETA antagonists may reduce morbidity as well as mortality in salt-sensitive hypertension.

Cited by 13 publications

References 31 publications

Salt Sensitivity of Blood Pressure

Salt Sensitivity of Blood Pressure

Increases in CSF [Na⁺] precede the increases in blood pressure in Dahl S rats and SHR on a high-salt diet

Acyl Glucuronidation and Glucosidation of a New and Selective Endothelin ET_AReceptor Antagonist in Human Liver Microsomes

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Marked reduction of mortality in salt-loaded Dahl salt- sensitive rats by the new, selective endothelin ETA receptor antagonist, J-105859

Abstract: J-105859 is a selective, potent, orally active ETA-selective antagonist ETA antagonists may reduce morbidity as well as mortality in salt-sensitive hypertension.

Cited by 13 publications

References 31 publications

Salt Sensitivity of Blood Pressure

Salt Sensitivity of Blood Pressure

Increases in CSF [Na+] precede the increases in blood pressure in Dahl S rats and SHR on a high-salt diet

Acyl Glucuronidation and Glucosidation of a New and Selective Endothelin ETAReceptor Antagonist in Human Liver Microsomes

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Product

Resources

About

Increases in CSF [Na⁺] precede the increases in blood pressure in Dahl S rats and SHR on a high-salt diet

Acyl Glucuronidation and Glucosidation of a New and Selective Endothelin ET_AReceptor Antagonist in Human Liver Microsomes