Antihypertensive and anti-inflammatory actions of combined azilsartan and chlorthalidone in Dahl salt-sensitive rats on a high-fat, high-salt diet

Chunhua Jin, Sean O'Boyle, Daniel T Kleven, Jennifer S. Pollock, David M. Pollock, John Jason White

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Metabolic syndrome (MetS) and chronic kidney disease are global health issues. Metabolic syndrome induces hypertension and commonly results in renal damage. The optimal therapy for hypertension in MetS is unknown. Thiazide diuretics are first-line therapy; however, these drugs may have untoward effects. In the present study we investigated the effects of azilsartan (AZL), chlorthalidone (CLTD) and their combination on blood pressure and renal injury in a rodent model with features of MetS. Dahl salt-sensitive rats were fed high-fat (36% fat), high-salt (4% NaCl) diet. Groups were then treated with vehicle, AZL (3 mg/kg per day), CLTD (5 mg/kg per day) or AZL + CLTD. Mean arterial pressure was recorded continuously by telemetry. After 26 days, rats were killed humanely and their kidneys were harvested for histology. Both AZL and CLTD attenuated the rise in blood pressure compared with vehicle and the combination further reduced blood pressure compared with CLTD alone. All treatments reduced proteinuria and albuminuria. Nephrinuria was prevented only in groups treated with AZL. Nephrinuria was 57% lower and proteinuria was 47% lower with combination therapy compared with AZL alone. All treatments reduced the number of inflammatory cells in the kidney. In conclusion, in our model, AZL and CLTD lower blood pressure and exhibit renal protective effects. Treatment with AZL offers additional protection, as evidenced by lower nephrinuria and plasma monocyte chemoattractant protein-1 levels. Combination therapy afforded the greatest protective effects and may be the best choice for hypertensive therapy in MetS.

Original languageEnglish (US)
Pages (from-to)579-588
Number of pages10
JournalClinical and Experimental Pharmacology and Physiology
Volume41
Issue number8
DOIs
StatePublished - Jan 1 2014

Fingerprint

Chlorthalidone
Inbred Dahl Rats
High Fat Diet
Antihypertensive Agents
Anti-Inflammatory Agents
Salts
Kidney
Blood Pressure
Therapeutics
Proteinuria
Fats
Hypertension
Sodium Chloride Symporter Inhibitors
Telemetry
Albuminuria
azilsartan
Chemokine CCL2
Chronic Renal Insufficiency
Blood Proteins
Rodentia

Keywords

  • Angiotensin receptor antagonists
  • Chronic kidney failure
  • Metabolic syndrome X

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

Cite this

Antihypertensive and anti-inflammatory actions of combined azilsartan and chlorthalidone in Dahl salt-sensitive rats on a high-fat, high-salt diet. / Jin, Chunhua; O'Boyle, Sean; Kleven, Daniel T; Pollock, Jennifer S.; Pollock, David M.; White, John Jason.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 41, No. 8, 01.01.2014, p. 579-588.

Research output: Contribution to journalArticle

@article{7007913e48aa4ca59c9d9bb706eadbd6,
title = "Antihypertensive and anti-inflammatory actions of combined azilsartan and chlorthalidone in Dahl salt-sensitive rats on a high-fat, high-salt diet",
abstract = "Metabolic syndrome (MetS) and chronic kidney disease are global health issues. Metabolic syndrome induces hypertension and commonly results in renal damage. The optimal therapy for hypertension in MetS is unknown. Thiazide diuretics are first-line therapy; however, these drugs may have untoward effects. In the present study we investigated the effects of azilsartan (AZL), chlorthalidone (CLTD) and their combination on blood pressure and renal injury in a rodent model with features of MetS. Dahl salt-sensitive rats were fed high-fat (36{\%} fat), high-salt (4{\%} NaCl) diet. Groups were then treated with vehicle, AZL (3 mg/kg per day), CLTD (5 mg/kg per day) or AZL + CLTD. Mean arterial pressure was recorded continuously by telemetry. After 26 days, rats were killed humanely and their kidneys were harvested for histology. Both AZL and CLTD attenuated the rise in blood pressure compared with vehicle and the combination further reduced blood pressure compared with CLTD alone. All treatments reduced proteinuria and albuminuria. Nephrinuria was prevented only in groups treated with AZL. Nephrinuria was 57{\%} lower and proteinuria was 47{\%} lower with combination therapy compared with AZL alone. All treatments reduced the number of inflammatory cells in the kidney. In conclusion, in our model, AZL and CLTD lower blood pressure and exhibit renal protective effects. Treatment with AZL offers additional protection, as evidenced by lower nephrinuria and plasma monocyte chemoattractant protein-1 levels. Combination therapy afforded the greatest protective effects and may be the best choice for hypertensive therapy in MetS.",
keywords = "Angiotensin receptor antagonists, Chronic kidney failure, Metabolic syndrome X",
author = "Chunhua Jin and Sean O'Boyle and Kleven, {Daniel T} and Pollock, {Jennifer S.} and Pollock, {David M.} and White, {John Jason}",
year = "2014",
month = "1",
day = "1",
doi = "10.1111/1440-1681.12250",
language = "English (US)",
volume = "41",
pages = "579--588",
journal = "Clinical and Experimental Pharmacology and Physiology",
issn = "0305-1870",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Antihypertensive and anti-inflammatory actions of combined azilsartan and chlorthalidone in Dahl salt-sensitive rats on a high-fat, high-salt diet

AU - Jin, Chunhua

AU - O'Boyle, Sean

AU - Kleven, Daniel T

AU - Pollock, Jennifer S.

AU - Pollock, David M.

AU - White, John Jason

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Metabolic syndrome (MetS) and chronic kidney disease are global health issues. Metabolic syndrome induces hypertension and commonly results in renal damage. The optimal therapy for hypertension in MetS is unknown. Thiazide diuretics are first-line therapy; however, these drugs may have untoward effects. In the present study we investigated the effects of azilsartan (AZL), chlorthalidone (CLTD) and their combination on blood pressure and renal injury in a rodent model with features of MetS. Dahl salt-sensitive rats were fed high-fat (36% fat), high-salt (4% NaCl) diet. Groups were then treated with vehicle, AZL (3 mg/kg per day), CLTD (5 mg/kg per day) or AZL + CLTD. Mean arterial pressure was recorded continuously by telemetry. After 26 days, rats were killed humanely and their kidneys were harvested for histology. Both AZL and CLTD attenuated the rise in blood pressure compared with vehicle and the combination further reduced blood pressure compared with CLTD alone. All treatments reduced proteinuria and albuminuria. Nephrinuria was prevented only in groups treated with AZL. Nephrinuria was 57% lower and proteinuria was 47% lower with combination therapy compared with AZL alone. All treatments reduced the number of inflammatory cells in the kidney. In conclusion, in our model, AZL and CLTD lower blood pressure and exhibit renal protective effects. Treatment with AZL offers additional protection, as evidenced by lower nephrinuria and plasma monocyte chemoattractant protein-1 levels. Combination therapy afforded the greatest protective effects and may be the best choice for hypertensive therapy in MetS.

AB - Metabolic syndrome (MetS) and chronic kidney disease are global health issues. Metabolic syndrome induces hypertension and commonly results in renal damage. The optimal therapy for hypertension in MetS is unknown. Thiazide diuretics are first-line therapy; however, these drugs may have untoward effects. In the present study we investigated the effects of azilsartan (AZL), chlorthalidone (CLTD) and their combination on blood pressure and renal injury in a rodent model with features of MetS. Dahl salt-sensitive rats were fed high-fat (36% fat), high-salt (4% NaCl) diet. Groups were then treated with vehicle, AZL (3 mg/kg per day), CLTD (5 mg/kg per day) or AZL + CLTD. Mean arterial pressure was recorded continuously by telemetry. After 26 days, rats were killed humanely and their kidneys were harvested for histology. Both AZL and CLTD attenuated the rise in blood pressure compared with vehicle and the combination further reduced blood pressure compared with CLTD alone. All treatments reduced proteinuria and albuminuria. Nephrinuria was prevented only in groups treated with AZL. Nephrinuria was 57% lower and proteinuria was 47% lower with combination therapy compared with AZL alone. All treatments reduced the number of inflammatory cells in the kidney. In conclusion, in our model, AZL and CLTD lower blood pressure and exhibit renal protective effects. Treatment with AZL offers additional protection, as evidenced by lower nephrinuria and plasma monocyte chemoattractant protein-1 levels. Combination therapy afforded the greatest protective effects and may be the best choice for hypertensive therapy in MetS.

KW - Angiotensin receptor antagonists

KW - Chronic kidney failure

KW - Metabolic syndrome X

UR - http://www.scopus.com/inward/record.url?scp=84906219674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906219674&partnerID=8YFLogxK

U2 - 10.1111/1440-1681.12250

DO - 10.1111/1440-1681.12250

M3 - Article

VL - 41

SP - 579

EP - 588

JO - Clinical and Experimental Pharmacology and Physiology

JF - Clinical and Experimental Pharmacology and Physiology

SN - 0305-1870

IS - 8

ER -