Selective effect of tempol on renal medullary hemodynamics in spontaneously hypertensive rats

The present study assessed the short- and long-term effect of tempol, a mem brane-permeable mimetic of superoxide dismutase, on renal medullary hemodyn amics in spontaneously hypertensive rats (SHR). Tempol was given in the dri nking water (1 mM) for 4 days or 7 wk (4-11 wk of age), and medullary blood flow (MBF) was measured over a wide range of renal arterial pressure by me ans of laser-Doppler flowmetry in anesthetized rats. In addition, the respo nse of the medullary circulation to angiotensin II (5-50 ng . kg(-1) . min( -1) iv) was determined in SHR treated for 4 days with tempol. Compared with control SHR, short- and long-term treatment with tempol decreased arterial pressure by similar to 20 mmHg and increased MBF by 35-50% without alterin g total renal blood flow (RBF) or autoregulation of RBF. Angiotensin II dec reased RBF and MBF dose dependently (similar to 30% at the highest dose) in control SHR. In SHR treated with tempol, angiotensin II decreased RBF (sim ilar to 30% at the highest dose) but did not alter MBF significantly. These data indicate that the antihypertensive effect of short- and long-term adm inistration of tempol in SHR is associated with a selective increase in MBF . Tempol also reduced the sensitivity of MBF to angiotensin II. Taken toget her, these data support the idea that tempol enhances vasodilator mechanism s of the medullary circulation, possibly by interacting with the nitric oxi de system. Increased MBF and reduced sensitivity of MBF to angiotensin II m ay contribute to the antihypertensive action of tempol in SHR.