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: 294/1/F205    most recent 00150.2007v1 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 Patterson, M. E. Articles by Mitchell, K. D. Search for Related Content PubMed PubMed Citation Articles by Patterson, M. E. Articles by Mitchell, K. D.

Renoprotective effects of neuronal NOS-derived nitric oxide and cyclooxygenase-2 metabolites in transgenic rats with inducible malignant hypertension

¹Department of Physiology, Tulane University Health Sciences Center, New Orleans, Louisiana; and ²Centre for Cardiovascular Science, The University of Edinburgh Medical School, Edinburgh, United Kingdom

Submitted 30 March 2007 ; accepted in final form 26 October 2007

The present study was performed to determine the effects of neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) inhibition on blood pressure and renal hemodynamics in transgenic rats with inducible ANG II-dependent malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Male Cyp1a1-Ren2 rats (n = 7) were fed a normal diet containing indole-3-carbinol (I3C; 0.3%) for 6–9 days to induce malignant hypertension. Mean arterial pressure (MAP) and renal hemodynamics were assessed in pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats before and during intravenous infusion of the nNOS inhibitor S-methyl-L-thiocitrulline (L-SMTC; 1 mg/h). In hypertensive Cyp1a1-Ren2 rats, L-SMTC increased MAP from 169 ± 3 to 188 ± 4 mmHg (P < 0.01), which was a smaller increase than in noninduced rats (124 ± 9 to 149 ± 9 mmHg, P < 0.01, n = 5). Additionally, L-SMTC decreased renal plasma flow (RPF) to a similar extent (–34 ± 13 vs. –35 ± 12%) in the hypertensive and normotensive rats (4.1 ± 0.2 to 2.7 ± 0.5 and 3.1 ± 0.3 to 2.0 ± 0.3 ml·min^–1·g^–1, respectively, P < 0.01) but did not alter glomerular filtration rate (GFR) in either group. In additional experiments, administration of the COX-2 inhibitor, nimesulide (3 mg/kg iv), during simultaneous infusion of L-SMTC decreased MAP in both hypertensive and noninduced rats (182 ± 2 to 170 ± 3 mmHg and 153 ± 3 to 140 ± 3 mmHg, respectively, P < 0.01). Nimesulide also decreased RPF (1.9 ± 0.2 to 0.8 ± 0.1 ml·min^–1·g^–1, P < 0.01) and GFR (0.9 ± 0.1 to 0.4 ± 0.1 ml·min^–1·g^–1, P < 0.01) in hypertensive rats but did not alter RPF or GFR in noninduced rats. The present findings demonstrate that both nNOS-derived NO and COX-2 metabolites exert pronounced renal vasodilator influences in hypertensive Cyp1a1-Ren2 rats. The data also indicate that the renal vasodilator effects of COX-2-derived prostanoids in hypertensive Cyp1a1-Ren2 rats are not dependent on nNOS activity.

kidney; nimesulide; S-methyl-L-thiocitrulline; renal hemodynamics; renin-angiotensin system; glomerular filtration rate; renal plasma flow