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Renoprotective effects of neuronal NOS-derived nitric oxide and cyclooxygenase-2 metabolites in transgenic rats with inducible malignant hypertension.
Am J Physiol Renal Physiol. 2008 Jan; 294(1):F205-11.AJ

Abstract

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 x min(-1) x 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 i.v.), 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 x min(-1) x g(-1), P < 0.01) and GFR (0.9 +/- 0.1 to 0.4 +/- 0.1 ml x min(-1) x 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.

Authors+Show Affiliations

Department of Physiology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17977909

Citation

Patterson, Matthew E., et al. "Renoprotective Effects of Neuronal NOS-derived Nitric Oxide and Cyclooxygenase-2 Metabolites in Transgenic Rats With Inducible Malignant Hypertension." American Journal of Physiology. Renal Physiology, vol. 294, no. 1, 2008, pp. F205-11.
Patterson ME, Mullins JJ, Mitchell KD. Renoprotective effects of neuronal NOS-derived nitric oxide and cyclooxygenase-2 metabolites in transgenic rats with inducible malignant hypertension. Am J Physiol Renal Physiol. 2008;294(1):F205-11.
Patterson, M. E., Mullins, J. J., & Mitchell, K. D. (2008). Renoprotective effects of neuronal NOS-derived nitric oxide and cyclooxygenase-2 metabolites in transgenic rats with inducible malignant hypertension. American Journal of Physiology. Renal Physiology, 294(1), F205-11.
Patterson ME, Mullins JJ, Mitchell KD. Renoprotective Effects of Neuronal NOS-derived Nitric Oxide and Cyclooxygenase-2 Metabolites in Transgenic Rats With Inducible Malignant Hypertension. Am J Physiol Renal Physiol. 2008;294(1):F205-11. PubMed PMID: 17977909.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renoprotective effects of neuronal NOS-derived nitric oxide and cyclooxygenase-2 metabolites in transgenic rats with inducible malignant hypertension. AU - Patterson,Matthew E, AU - Mullins,John J, AU - Mitchell,Kenneth D, Y1 - 2007/10/31/ PY - 2007/11/6/pubmed PY - 2008/3/5/medline PY - 2007/11/6/entrez SP - F205 EP - 11 JF - American journal of physiology. Renal physiology JO - Am. J. Physiol. Renal Physiol. VL - 294 IS - 1 N2 - 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 x min(-1) x 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 i.v.), 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 x min(-1) x g(-1), P < 0.01) and GFR (0.9 +/- 0.1 to 0.4 +/- 0.1 ml x min(-1) x 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. SN - 1931-857X UR - https://www.unboundmedicine.com/medline/citation/17977909/Renoprotective_effects_of_neuronal_NOS_derived_nitric_oxide_and_cyclooxygenase_2_metabolites_in_transgenic_rats_with_inducible_malignant_hypertension_ L2 - http://www.physiology.org/doi/full/10.1152/ajprenal.00150.2007?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -