NO-independent mechanism mediates tempol-induced renal vasodilation in SHR.
We investigated whether tempol, a superoxide dismutase mimetic, affected renal hemodynamics and arterial pressure in spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats. We also examined whether tempol affected exaggerated renal vasoconstrictor responses to ANG II in SHR. To test whether the effects of tempol were due to a restored NO system, we used the NOS inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME). Renal blood flow (RBF) and mean arterial pressure (MAP) were measured in vivo by electromagnetic flowmetry and arterial catheterization in 10- to 12-wk-old anesthetized SHR and SD rats. Systolic arterial pressure (SAP) was measured in conscious rats using the tail cuff method. Tempol (1 mM) was given in the drinking water to SD (SD-T) and SHR (SHR-T) 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 intravenously for 15-20 min. Renal vascular resistance (RVR) was elevated in SHR-C compared with SD-C. In SHR-T, baseline RVR was not different from SD-C and SD-T rats. Tempol had no effect on RVR in SD. L-NAME 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 rats but had no effect on the ANG II responses in the other groups. Thus L-NAME treatment did not influence tempol's effects on baseline RVR or ANG II responses. 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 greater in SHR-T rats, it is not likely that the elevated renal resistance and ANG II sensitivity in SHR are due to reactive oxygen species-induced quenching of nitric oxide.
de Richelieu
Louise Tilma
LT
Division of Renal and Cardiovascular Research, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Denmark.
Sorensen
Charlotte Mehlin
CM
Holstein-Rathlou
Niels-Henrik
NH
Salomonsson
Max
M
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects*; D013113:Spin Labels; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D003497:Cyclic N-Oxides; D013113:Spin Labels; D000804:Angiotensin II; D009569:Nitric Oxide; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester