Published Online
on May 31, 2005

A more recent version of this article appeared on July 1, 2005

This Article Full Text (PDF) All Versions of this Article: 46/1/82    most recent 01.HYP.0000169152.59854.36v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by LaMarca, B. B. D. Articles by Granger, J. P. Search for Related Content PubMed PubMed Citation Articles by LaMarca, B. B. D. Articles by Granger, J. P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure High Risk Pregnancy Related Collections Animal models of human disease Growth factors/cytokines Endothelium/vascular type/nitric oxide

Submitted on November 30, 2004
Revised on January 5, 2005

Role of Endothelin in Mediating Tumor Necrosis Factor-Induced Hypertension in Pregnant Rats

B. Babbette D. LaMarca; Kathy Cockrell; Elizabeth Sullivan; William Bennett; and Joey P. Granger^*

From the Departments of Physiology and Obstetrics/Gynecology and Center for Excellence in Cardiovascular-Renal Research University of Mississippi Medical Center, Jackson, Miss.

^* To whom correspondence should be addressed. E-mail: jgranger{at}physiology.umsmed.edu.

Abstract--Hypertension during preeclampsia is associated with an increase in plasma levels of tumor necrosis factor (TNF)-, a cytokine known to contribute to endothelial dysfunction. Recently, our laboratory reported that a 2-fold increase in plasma TNF- produces hypertension in pregnant rats. Endothelin is also elevated in preeclampsia and endothelin synthesis is enhanced by TNF-. The purpose of this study was to determine the role of endothlelin in mediating TNF--induced hypertension in pregnant rats. To achieve this goal, TNF- (50 ng/d for 5 days) was infused into control pregnant rats and pregnant rats treated with an endothelin receptor A antagonist, ABT 627 (5 mg/kg per day for 5 days). At day 19 of gestation, arterial pressure was measured and aorta, kidneys, and placentas were harvested. Infusion of TNF- into pregnant rats increased plasma concentration of TNF- (13.5±0.8 to 28.0±3.7 pg/mL) and arterial pressure (101±2 to 122±1 mm Hg). The increase in arterial pressure was associated with an increase in preproendothelin mRNA expression in placenta, aorta, and kidneys measured by real-time polymerase chain reaction (PCR). Pretreatment with the endothelin receptor A antagonist completely abolished the blood pressure response to TNF- in pregnant rats (105±1 versus 97±2 mm Hg). In sharp contrast, the ET_A receptor antagonist had no effect on arterial pressure in normal pregnant rats (97±2 versus 101±2 mm Hg). Moreover, chronic infusion of TNF- had no significant effect on arterial pressure or renal preproendothelin levels in virgin rats. These results suggest an important role for endothelin in mediating TNF--induced hypertension in pregnant rats.

Key words: blood pressure • endothelin • preeclampsia • pregnancy

This article has been cited by other articles:

				D. D. Briana and A. Malamitsi-Puchner Reviews: Adipocytokines in Normal and Complicated Pregnancies Reproductive Sciences, October 1, 2009; 16(10): 921 - 937. [Abstract] [PDF]

				W. Wang, S. Bansal, S. Falk, D. Ljubanovic, and R. Schrier Ghrelin protects mice against endotoxemia-induced acute kidney injury Am J Physiol Renal Physiol, October 1, 2009; 297(4): F1032 - F1037. [Abstract] [Full Text] [PDF]

				B. LaMarca, M. Parrish, L. F. Ray, S. R. Murphy, L. Roberts, P. Glover, G. Wallukat, K. Wenzel, K. Cockrell, J. N. Martin Jr, et al. Hypertension in Response to Autoantibodies to the Angiotensin II Type I Receptor (AT1-AA) in Pregnant Rats: Role of Endothelin-1 Hypertension, October 1, 2009; 54(4): 905 - 909. [Abstract] [Full Text] [PDF]

				M. Venegas-Pont, J. C. Sartori-Valinotti, C. Maric, L. C. Racusen, P. H. Glover, G. R. McLemore Jr., A. V. Jones, J. F. Reckelhoff, and M. J. Ryan Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2009; 296(4): R1282 - R1289. [Abstract] [Full Text] [PDF]

				F. R. C. Giachini, S. M. Zemse, F. S. Carneiro, V. V. Lima, Z. N. Carneiro, G. E. Callera, A. Ergul, R. C. Webb, and R. C. Tostes Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H489 - H496. [Abstract] [Full Text] [PDF]

				B. LaMarca, J. Speed, L. Fournier, S. A. Babcock, H. Berry, K. Cockrell, and J. P. Granger Hypertension in Response to Chronic Reductions in Uterine Perfusion in Pregnant Rats: Effect of Tumor Necrosis Factor-{alpha} Blockade Hypertension, December 1, 2008; 52(6): 1161 - 1167. [Abstract] [Full Text] [PDF]

				B. D. LaMarca, J. Gilbert, and J. P. Granger Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia Hypertension, April 1, 2008; 51(4): 982 - 988. [Full Text] [PDF]

				H. I. Abdullah, P. L. Pedraza, J. C. McGiff, and N. R. Ferreri CaR activation increases TNF production by mTAL cells via a Gi-dependent mechanism Am J Physiol Renal Physiol, February 1, 2008; 294(2): F345 - F354. [Abstract] [Full Text] [PDF]

				J. S. Gilbert, M. J. Ryan, B. B. LaMarca, M. Sedeek, S. R. Murphy, and J. P. Granger Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H541 - H550. [Abstract] [Full Text] [PDF]

				A. A. Elmarakby, J. E. Quigley, J. D. Imig, J. S. Pollock, and D. M. Pollock TNF-{alpha} inhibition reduces renal injury in DOCA-salt hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R76 - R83. [Abstract] [Full Text] [PDF]

				F. Herse, R. Dechend, N. K. Harsem, G. Wallukat, J. Janke, F. Qadri, L. Hering, D. N. Muller, F. C. Luft, and A. C. Staff Dysregulation of the Circulating and Tissue-Based Renin-Angiotensin System in Preeclampsia Hypertension, March 1, 2007; 49(3): 604 - 611. [Abstract] [Full Text] [PDF]

				G. Gadonski, B. B. D. LaMarca, E. Sullivan, W. Bennett, D. Chandler, and J. P. Granger Hypertension Produced by Reductions in Uterine Perfusion in the Pregnant Rat: Role of Interleukin 6 Hypertension, October 1, 2006; 48(4): 711 - 716. [Abstract] [Full Text] [PDF]

				J. P. Granger An emerging role for inflammatory cytokines in hypertension Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H923 - H924. [Full Text] [PDF]

				L. Roberts, B. B. D. LaMarca, L. Fournier, J. Bain, K. Cockrell, and J. P. Granger Enhanced Endothelin Synthesis by Endothelial Cells Exposed to Sera From Pregnant Rats With Decreased Uterine Perfusion Hypertension, March 1, 2006; 47(3): 615 - 618. [Abstract] [Full Text] [PDF]