(Hypertension. 2001;37:77.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Systemic and Regional Hemodynamic Responses to Tempol in Angiotensin II–Infused Hypertensive Rats
From the Department of Pharmacology (A.N., T.F., M.R., R.-X.T., S.K., Y.A.) and Research Equipment Center (Y.F.), Kagawa Medical University, Kagawa, Japan.
Correspondence to Youichi Abe, MD, PhD, Department of Pharmacology, Kagawa Medical University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. E-mail yakuri{at}kms.ac.jp
Abstract—Recent studies have
indicated that angiotensin II (Ang II) can stimulate
oxidative stress. The present study was conducted to assess the
contribution of oxygen radicals to hypertension and regional
circulation during Ang II–induced hypertension. With radioactive
microspheres, the responses of systemic and regional
hemodynamics to the membrane-permeable,
metal-independent superoxide dismutase mimetic
4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol) were assessed in
conscious Ang II–infused hypertensive rats. Ang II–infused rats (80
ng/min SC for 12 days: n=25) showed higher mean arterial
pressure (MAP: 161±4 mm Hg) and total peripheral
resistance (TPR: 1.59±0.08 mm Hg ·
min-1 · mL-1) than vehicle-infused
normotensive rats (116±3 mm Hg and 0.95±0.04 mm Hg
· min-1 · mL-1, respectively; n=23).
The blood flow rates in the brain, spleen, large intestine, and skin
were significantly reduced in Ang II–infused rats compared with
vehicle-infused rats, whereas rates in the lung, heart, liver, kidney,
stomach, small intestine, mesenterium, skeletal muscle, and testis were
similar. Vascular resistance was significantly increased in every organ
studied except the lung, in which the resistance was similar. Tempol
(216 µmol/kg IV) significantly reduced MAP by 30±4% from
158±7 to 114±5 mm Hg and TPR by 35±6% from 1.57±0.17 to
0.95±0.04 mm Hg · min-1 ·
g-1 in Ang II–infused rats (n=9) but had no effect on
these parameters in vehicle-infused rats (n=8). In Ang
II–infused rats, tempol did not affect regional blood flow but
significantly decreased vascular resistance in the brain (29±6%),
heart (31±6%), liver (37±7%), kidney (30±7%), small intestine
(38±6%), and large intestine (47±7%). Ang II–infused hypertensive
rats showed doubled vascular superoxide production (assessed
with lucigenin chemiluminescence), which was normalized by treatment
with tempol (3 mmol/L, n=7). Further studies showed that the NO
synthase inhibitor,
N
-nitro-L-arginine methyl
ester (11 µmol · kg-1 ·
min-1 IV, n=11) markedly attenuated the systemic and
regional hemodynamic responses of tempol in Ang
II–infused rats. These results suggest that in this model of
hypertension, oxidative stress may have contributed to the alterations
in systemic blood pressure and regional vascular resistance through
inactivation of NO.
Key Words: angiotensin II • oxygen radicals • hypertension, renovascular • nitric oxide • hemodynamics • microspheres • tempol
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