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: 293/5/H2644    most recent 00748.2007v1 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 HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Welch, W. J. Articles by Wilcox, C. S. Search for Related Content PubMed PubMed Citation Articles by Welch, W. J. Articles by Wilcox, C. S.

CALL FOR PAPERS
Cardiovascular-Renal Mechanisms in Health and Disease

Roles of vasoconstrictor prostaglandins, COX-1 and -2, and AT₁, AT₂, and TP receptors in a rat model of early 2K,1C hypertension

Division of Nephrology and Hypertension, Georgetown University, Washington DC

Submitted 28 June 2007 ; accepted in final form 30 August 2007

Angiotensin (ANG) II activating type 1 receptors (AT₁Rs) enhances superoxide anion (O₂^–) and arachidonate (AA) formation. AA is metabolized by cyclooxygenases (COXs) to PGH₂, which is metabolized by thromboxane (Tx)A₂ synthase to TxA₂ or oxidized to 8-isoprostane PGF₂ (8-Iso) by O₂^–. PGH₂, TxA₂, and 8-Iso activate thromboxane-prostanoid receptors (TPRs). We investigated whether blood pressure in a rat model of early (3 wk) two-kidney, one-clip (2K,1C) Goldblatt hypertension is maintained by AT₁Rs or AT₂Rs, driving COX-1 or -2-dependent products that activate TPRs. Compared with sham-operated rats, 2K,1C Goldblatt rats had increased mean arterial pressure (MAP; 120 ± 4 vs. 155 ± 3 mmHg; P < 0.001), plasma renin activity (PRA; 22 ± 7 vs. 48 ± 5 ng·ml^–1·h^–1; P < 0.01), plasma malondialdehyde (1.07 ± 0.05 vs. 1.58 ± 0.16 nmol/l; P < 0.01), and TxB₂ excretion (26 ± 4 vs. 51 ± 7 ng/24 h; P < 0.01). Acute graded intravenous doses of benazeprilat (angiotensin-converting enzyme inhibitor) reduced MAP at 20 min (–36 ± 5 mmHg; P < 0.001) and excretion of TxA₂ metabolites. Indomethacin (nonselective COX antagonist) or SC-560 (COX-1 antagonist) reduced MAP at 20 min (–25 ± 5 and –28 ± 7 mmHg; P < 0.001), whereas valdecoxib (COX-2 antagonist) was ineffective (–9 ± 5 mmHg; not significant). Losartan (AT₁R antagonist) or SQ-29548 (TPR antagonist) reduced MAP at 150 min (–24 ± 6 and –22 ± 3 mmHg; P < 0.001), whereas PD-123319 (AT₂R antagonist) was ineffective. Acute blockade of TPRs, COX-1, or COX-2 did not change PRA, but TxB₂ generation by the clipped kidney was reduced by blockade of COX-1 and increased by blockade of COX-2. 2K,1C hypertension in rats activates renin, O₂^–, and vasoconstrictor PGs. Hypertension is maintained by AT₁Rs and by COX-1, but not COX-2, products that activate TPRs.

renovascular hypertension; angiotensin receptor blocker; thromboxane A₂; isoprostane; angiotensin-converting enzyme inhibition

This article has been cited by other articles:

				Z. Ying, F. R.C. Giachini, R. C. Tostes, and R. C. Webb Salicylates dilate blood vessels through inhibiting PYK2-mediated RhoA/Rho-kinase activation Cardiovasc Res, July 1, 2009; 83(1): 155 - 162. [Abstract] [Full Text] [PDF]

				A. Virdis, R. Colucci, D. Versari, N. Ghisu, M. Fornai, L. Antonioli, E. Duranti, E. Daghini, C. Giannarelli, C. Blandizzi, et al. Atorvastatin Prevents Endothelial Dysfunction in Mesenteric Arteries From Spontaneously Hypertensive Rats: Role of Cyclooxygenase 2-Derived Contracting Prostanoids Hypertension, June 1, 2009; 53(6): 1008 - 1016. [Abstract] [Full Text] [PDF]

				C. S. Wilcox and A. Pearlman Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides Pharmacol. Rev., December 1, 2008; 60(4): 418 - 469. [Abstract] [Full Text] [PDF]