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

M. E. Patterson, J. J. Mullins, K. D. Mitchell

Research output: Contribution to journalArticlepeer-review

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 Cyp1a1Ren2 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 center dot min(-1)center dot 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 center dot min(-1)center dot g(-1), P <0.01) and GFR (0.9 +/- 0.1 to 0.4 +/- 0.1 ml center dot min(-1)center dot 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.
Original languageEnglish
Pages (from-to)F205-F211
JournalAmerican Journal of Physiology - Renal Physiology
Volume294
Issue number1
DOIs
Publication statusPublished - Jan 2008

Keywords

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

Fingerprint Dive into the research topics of 'Renoprotective effects of neuronal NOS-derived nitric oxide and cyclooxygenase-2 metabolites in transgenic rats with inducible malignant hypertension'. Together they form a unique fingerprint.

Cite this