Genetic Effect of Endothelin and Angiotensin Receptor Blockade on Renal Injury in Salt-Sensitive and Salt-Resistant Hypertension

Tsung-Ming Lee, Nen-Chung Chang

Research output: Contribution to journalArticle

Abstract

Proteinuria was inhibited by angiotensin receptor antagonists with a variable response. It remained unclear whether failure of some experimental models of hypertension to respond to treatment with the angiotensin antagonists may be due to genetic background. To investigate genetic effects on renal injuries in response to endothelin-A blocker (ABT-627), endothelin-B blocker (A-192621), and angiotensin receptor blocker (valsartan), we compared deoxycorticosterone acetate (DOCA)-salt rats and spontaneously hypertensive rats (SHR) with the genetic control Wistar-Kyoto rats. Drugs were initiated after hypertension was established. Compared with controls, arterial pressure increased in both strains and was not decreased after 4 weeks’ drug intervention. In both hypertensive strains, renal creatinine clearance decreased, and urinary excretion of protein, interstitial fibrosis, and TGF-β mRNA levels were significantly increased. In vehicle-treated DOCA-salt rats, such damage was overcome by ABT-627 and substantially blunted by valsartan, but not with A-192621. The improvement degree of proteinuria in DOCA-salt rats was significantly greater in rats treated by ABT-627 than those treated by valsartan. In SHR, valsartan, but not ABT-627, can significantly attenuate the renal injury. These results strongly support the important role of genetic predisposition in different renal responses to treatments. In DOCA-salt rats, endothelin-A receptor– and angiotensin receptor-mediated action plays an important role in the pathogenesis of renal damage. On the other hand, only angiotensin receptor antagonist is useful for treatment in SHR.
Original languageEnglish
Pages (from-to)786.1-786.1
JournalFASEB Journal
Volume24
Issue number1 Supplement
Publication statusPublished - Apr 1 2010

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Valsartan
Endothelin Receptors
Angiotensin Receptors
Desoxycorticosterone
Rats
Salts
A 192621
Angiotensin Receptor Antagonists
Hypertension
Kidney
Acetates
Inbred SHR Rats
Wounds and Injuries
Endothelins
Proteinuria
Endothelin A Receptors
Inbred WKY Rats
Angiotensins
Genetic Predisposition to Disease
Pharmaceutical Preparations

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Genetic Effect of Endothelin and Angiotensin Receptor Blockade on Renal Injury in Salt-Sensitive and Salt-Resistant Hypertension. / Lee, Tsung-Ming; Chang, Nen-Chung.

In: FASEB Journal, Vol. 24, No. 1 Supplement, 01.04.2010, p. 786.1-786.1.

Research output: Contribution to journalArticle

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