HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/F1096    most recent 00369.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Francois, H. Articles by Coffman, T. M. Search for Related Content PubMed PubMed Citation Articles by Francois, H. Articles by Coffman, T. M.

A role for the thromboxane receptor in L-NAME hypertension

Divisions of ¹Nephrology and ³Cardiology, Department of Medicine, Duke University and Durham Veterans Affairs Medical Centers, Durham, North Carolina; and ²Department of Pathology, University of Miami, Miami, Florida

Submitted 6 August 2007 ; accepted in final form 4 August 2008

Actions of the lipid mediator thromboxane (Tx) A₂ acting through the TP receptor contribute to the pathogenesis of cardiovascular disease. To further explore the role of TxA₂ in hypertension, we examined the consequences of deficiency of the TP receptor on the course of hypertension associated with endothelial dysfunction and salt sensitivity. To this end, the nitric oxide synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) was administered to TP-deficient (Tp^–/–) and wild-type (Tp^+/+) control mice in drinking water for 21 wk along with a high-salt (HS; 6% NaCl) diet. Administration of L-NAME increased urinary excretion of TxB₂ to a similar extent in both Tp^+/+ and Tp^–/– animals. L-NAME also caused significant and sustained elevations in blood pressure that reached a maximum between weeks 3 and 6. However, the severity of hypertension was attenuated in the Tp^–/– mice throughout the study period (P < 0.001). At the end of the study, the wild-type mice developed significant cardiac hypertrophy (23.6 ± 2% increase in heart-to-body weight ratio). The severity of cardiac hypertrophy was attenuated in the TP-deficient group (11.1 ± 2.6%; P < 0.05). In contrast, kidney hypertrophy was exaggerated in the Tp^–/– mice compared with controls (37.1 ± 5.4 vs. 12.3 ± 2.3%; P < 0.01). Moreover, the severity of glomerulosclerosis, tubule vacuolization, and interstitial chronic inflammation was also enhanced in the Tp^–/– group (P < 0.01). Thus, in L-NAME hypertension, TP receptors contribute to elevated blood pressure and cardiac hypertrophy. In this model, TP receptors also provided unexpected protection against kidney injury.

cardiovascular disease; cardiac hypertrophy; prostanoids; renal injury