JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Li, P.
Right arrow Articles by Brosnihan, K. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, P.
Right arrow Articles by Brosnihan, K. B.

Vol. 281, Issue 3, 1065-1070, 1997

Nonpeptide Angiotensin II Antagonist Losartan Inhibits Thromboxane A2-Induced Contractions in Canine Coronary Arteries1

Ping Li, Carlos M. Ferrario and K. Bridget Brosnihan

The Hypertension Center, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina

We investigated the selectivity of a nonpeptide angiotensin II AT1 receptor antagonist losartan for the vascular thromboxane A2 (TxA2)/prostaglandin endoperoxide (PGH2) receptor in canine coronary arteries. Isometric tension was measured in canine coronary artery rings suspended in organ chambers perfused with 95% O2/5% CO2. The TxA2 analog, U46619, produced dose-dependent vasoconstriction in coronary rings (EC50, 10.6 ± 0.9 nmol/l). Pretreatment with losartan (10-8-10-5 mol/l) inhibited the contractile response of U46619 and shifted the concentration-response curve to the right in dose-dependent manner. The EC50 of U46619 was increased 3- and 13-fold in the presence of both 1 and 10 µmol/l of losartan without a change in maximal contraction. The selective TxA2/PGH2 receptor antagonist SQ29548 blocked U46619-induced contraction with greater potency than losartan in isolated coronary arteries. The active metabolite of losartan EXP3174 at 1 µmol/l did competitively block U46619-induced contractions in canine coronary rings. In contrast, the contractile responses produced by U46619 were unaffected by exposure to the nonpeptide AT1 receptor antagonist CV11974, the AT2 receptor antagonist PD123319 or the nonselective peptide angiotensin II antagonist Sar1Thr8-Ang II, each at 1 µmol/l concentration. These data indicate that losartan and its active metabolite EXP3174 are antagonists to the TxA2/PGH2 receptor in canine coronary arteries. The antagonistic effect of losartan and EXP3174 on the vascular TxA2/PGH2 receptor may contribute to the long-term blood pressure-lowering effects of angiotensin antagonists in hypertension.

Copyright © by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Journal of Renin-Angiotensin-Aldosterone SystemHome page
J. L Reid
Review: Molecular-specific effects of angiotensin II antagonists: clinical relevance to treating hypertension?
Journal of Renin-Angiotensin-Aldosterone System, March 1, 2005; 6(1): 15 - 24.
[Abstract] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. Nakamura, D. B. Averill, M. C. Chappell, D. I. Diz, K. B. Brosnihan, and C. M. Ferrario
Angiotensin receptors contribute to blood pressure homeostasis in salt-depleted SHR
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2003; 284(1): R164 - R173.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
I. Kucharewicz, R. Pawlak, T. Matys, D. Pawlak, and W. Buczko
Antithrombotic Effect of Captopril and Losartan Is Mediated by Angiotensin-(1-7)
Hypertension, November 1, 2002; 40(5): 774 - 779.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. Raiden, K. Nahmod, V. Nahmod, G. Semeniuk, Y. Pereira, C. Alvarez, M. Giordano, and J. R. Geffner
Nonpeptide Antagonists of AT1 Receptor for Angiotensin II Delay the Onset of Acute Respiratory Distress Syndrome
J. Pharmacol. Exp. Ther., October 1, 2002; 303(1): 45 - 51.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
J. Sadoshima
Novel AT1 Receptor-Independent Functions of Losartan
Circ. Res., April 19, 2002; 90(7): 754 - 756.
[Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
M.-H. Liu, H. S. Floten, A. P. Furnary, A. P.C. Yim, and G.-W. He
Inhibition of vasoconstriction by angiotensin receptor antagonist GR117289C in arterial grafts
Ann. Thorac. Surg., December 1, 2000; 70(6): 2064 - 2069.
[Abstract] [Full Text] [PDF]

Home page
 Journal of Renin-Angiotensin-Aldosterone SystemHome page
A. Nunez, J. Gomez, L. R. Zalba, M. Monton, A. Jimenez, S. Velasco, A. Lopez-Blaya, A. Celdran Uriarte, S. Casado, and A. Lopez-Farre
Losartan inhibits in vitro platelet activation: comparison with candesartan and valsartan
Journal of Renin-Angiotensin-Aldosterone System, June 1, 2000; 1(2): 175 - 179.
[Abstract] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
P. Li, M. Fukuhara, D. I. Diz, C. M. Ferrario, and K. B. Brosnihan
Novel Angiotensin II AT1 Receptor Antagonist Irbesartan Prevents Thromboxane A2-Induced Vasoconstriction in Canine Coronary Arteries and Human Platelet Aggregation
J. Pharmacol. Exp. Ther., January 1, 2000; 292(1): 238 - 246.
[Abstract] [Full Text]

Home page
 Cardiovasc ResHome page
J. Kalliovalkama, P. Jolma, J.-P. Tolvanen, M. Kahonen, N. Hutri-Kahonen, X. Wu, P. Holm, and I. Porsti
Arterial function in nitric oxide-deficient hypertension: influence of long-term angiotensin II receptor antagonism
Cardiovasc Res, June 1, 1999; 42(3): 773 - 782.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics.