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Department of Physiology, University of Western Ontario, London, Ontario, Canada N6A 5C1
The present study
assessed the short- and long-term effect of tempol, a
membrane-permeable mimetic of superoxide dismutase, on renal medullary
hemodynamics in spontaneously hypertensive rats (SHR). Tempol was given
in the drinking 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 means of laser-Doppler flowmetry in anesthetized
rats. In addition, the response of the medullary circulation to
angiotensin II (5-50 ng · kg
1 · min1 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 ~20 mmHg and increased MBF by 35-50% without altering total renal blood flow (RBF) or autoregulation of RBF. Angiotensin II decreased RBF and MBF dose dependently (~30% at the
highest dose) in control SHR. In SHR treated with tempol, angiotensin
II decreased RBF (~30% at the highest dose) but did not alter MBF
significantly. These data indicate that the antihypertensive effect of
short- and long-term administration of tempol in SHR is associated with
a selective increase in MBF. Tempol also reduced the sensitivity of MBF
to angiotensin II. Taken together, these data support the idea that
tempol enhances vasodilator mechanisms of the medullary circulation,
possibly by interacting with the nitric oxide system. Increased MBF and
reduced sensitivity of MBF to angiotensin II may contribute to the
antihypertensive action of tempol in SHR.
arterial pressure; nitric oxide; renal medulla; kidney; hypertension; angiotensin II
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