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Am J Physiol Renal Physiol (July 20, 2005). doi:10.1152/ajprenal.00116.2005
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Submitted on March 23, 2005
Accepted on July 14, 2005

NO independent mechanism mediates tempol induced renal vasodilation in SHR

Louise Tilma de Richelieu1, Charlotte Mehlin Sorensen1, Niels-Henrik Holstein-Rathlou1, and Max Salomonsson1*

1 Division of Renal and Cardiovascular Research, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

* To whom correspondence should be addressed. E-mail: maxsalomon{at}mfi.ku.dk.

Objectives: We investigated if tempol, a superoxide dismutase mimetic, affected renal hemodynamics and arterial pressure in spontaneously hypertensive rats (SHR) and Spague-Dawley (SD) rats. We also examined whether tempol affected exaggerated renal vasoconstrictor responses to Angiotensin II (Ang II) in SHR. To test whether the effects of tempol were due to a restored NO system we used the NOS inhibitor Nw-nitro-L-arginin methyl ester (L-NAME). Methods: Renal blood flow (RBF) and mean arterial pressure (MAP) were measured in vivo by electromagnetic flowmetry and arterial catheterization in 10-12 week old anesthetized SHR and SD rats. Systolic arterial pressure (SAP) was measured in conscious rats using the tail cuff method. Tempol was given in the drinking water to SD (SD-T) and SHR (SHR-T) (1 mM) for 5-7 days for RBF measurements and for 15 days for SAP measurements. Age matched SD (SD-C) and SHR (SHR-C) were used as controls. Ang II (1-4 ng) was administered as a bolus via a renal artery catheter. L-NAME was administered i.v. for 15-20 minutes. Results: RVR was elevated in SHR-C compared to SD-C. In SHR-T baseline RVR was not different from SD-C and SD-T. Tempol had no effect on RVR in SD. L-NA-ME elevated RVR to the same extent in all four groups. Arterial pressure was not affected by tempol. The RVR responses to Ang II were higher in SHR-C than in the SD-C group. Ang II responses were not different between SHR-T and SD-T. Overall tempol reduced the renovascular responses to Ang II in SHR. L-NAME elevated the effects of Ang II in SD-C, but had no effect on the Ang II responses in the other groups. Thus, L-NAME treatment did not influence the tempol effects on baseline RVR or Ang II responses. Conclusions: We conclude, that in SHR, tempol has a significant renal vasodilator effect, and that it normalizes the increased renovascular Ang II sensitivity. As the effects of L-NAME are not larger in SHR-T, it is not likely that the elevated renal resistance and Ang II sensitivity in SHR is due to ROS induced quenching of NO.




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