Kyle M Ware 1 , Jay C Vance 2 , Navin Muni 1 , Lee A Hebert 2 , Anjali A Satoskar 1 , Gyongyi Nadasdy 1 , Iouri Ivanov 1 , Tibor Nadasdy 1 , Brad H Rovin 2 , Sergey V Brodsky 3 Show Affiliations »
Abstract
BACKGROUND: Hypertension is a common comorbidity in patients with chronic kidney disease (CKD). We reported earlier that oral anticoagulants, including warfarin and dabigatran, may induce acute kidney injury. No effects of oral anticoagulants on blood pressure (BP) have been previously reported. The aim of this study was to examine in detail the relationship of anticoagulant therapy and BP in rats. METHODS: Sham-operated and 5/6 nephrectomy rats were treated with different doses of oral anticoagulants (warfarin and dabigatran), superoxide scavenger N-acetylcysteine (NAC), vitamin K, and protease activated receptor 1 (PAR-1) inhibitor SCH79797. BP was measured by a tail cuff daily. RESULTS: Warfarin and dabigatran both increased systolic BP in sham-operated and 5/6 nephrectomy rats in a dose-dependent manner. SCH79797 also increased systolic BP in a dose-dependent manner. Vitamin K prevented warfarin-induced increase in BP but did not affect BP when administered alone. NAC delayed the warfarin-associated increase in BP. Warfarin effects on BP were similar in 5/6 nephrectomy rats with different CKD stages. CONCLUSIONS: Both warfarin and dabigatran increase systolic BP in rats. The mechanism of this effect is not clear, but our data suggest that it is related to decreased thrombin activity associated with anticoagulant treatment. The superoxide scavenger NAC delayed, but did not prevent, warfarin-induced hypertension. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
BACKGROUND: Hypertension is a common comorbidity in patients with chronic kidney disease (CKD ). We reported earlier that oral anticoagulants, including warfarin and dabigatran , may induce acute kidney injury . No effects of oral anticoagulants on blood pressure (BP) have been previously reported. The aim of this study was to examine in detail the relationship of anticoagulant therapy and BP in rats . METHODS: Sham-operated and 5/6 nephrectomy rats were treated with different doses of oral anticoagulants (warfarin and dabigatran ), superoxide scavenger N-acetylcysteine (NAC ), vitamin K , and protease activated receptor 1 (PAR-1 ) inhibitor SCH79797 . BP was measured by a tail cuff daily. RESULTS: Warfarin and dabigatran both increased systolic BP in sham-operated and 5/6 nephrectomy rats in a dose-dependent manner. SCH79797 also increased systolic BP in a dose-dependent manner. Vitamin K prevented warfarin -induced increase in BP but did not affect BP when administered alone. NAC delayed the warfarin -associated increase in BP. Warfarin effects on BP were similar in 5/6 nephrectomy rats with different CKD stages. CONCLUSIONS: Both warfarin and dabigatran increase systolic BP in rats . The mechanism of this effect is not clear, but our data suggest that it is related to decreased thrombin activity associated with anticoagulant treatment. The superoxide scavenger NAC delayed, but did not prevent, warfarin -induced hypertension . © American Journal of Hypertension , Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Entities: Chemical
Disease
Gene
Species
Keywords:
5/6 nephrectomy.; blood pressure; chronic kidney injury; dabigatran; hypertension; warfarin
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Year: 2014
PMID： 25023204 DOI： 10.1093/ajh/hpu129
Source DB: PubMed Journal: Am J Hypertens ISSN： 0895-7061 Impact factor: 2.689