From the Graduate Institute of Life Sciences and Departments of Medical
Research (T.-C.C.), Pharmacology (M.-H.Y.), Anesthesiology (C.-Y.L.),
Tri-Service General Hospital; the National Defense Medical Center; and the
Division of Cardiology, Veterans General Hospital (Y.-A.D.), Taipei, Republic
of China.
Correspondence to Yu-An Ding, Division of Cardiology, Veterans General Hospital, 201, Sec. 2, Shih-Pai Rd. Taipei, Taiwan, ROC.
Abstract—The activity and protein
expression of endothelial nitric oxide synthase (eNOS)
and inducible NOS (iNOS) were investigated during the development of
hypertension in spontaneously hypertensive rats (SHR). SHR and
Wistar-Kyoto rats (WKY) were studied at three different ages: 4, 14 to
17, and 63 weeks of age. After treatment with saline or
lipopolysaccharide (LPS, 10 mg/kg IV) for 3 hours, the aortas
were removed for measurement of NOS activity and protein expression
assay by [3H]-L-citrulline formation method
and Western blot analysis, respectively. Plasma levels of
nitrite/nitrate
(NO2-/NO3-) and tumor
necrosis factor-
© 1998 American Heart Association, Inc.
Scientific Contributions
Alterations of Nitric Oxide Synthase Expression With Aging and Hypertension in Rats
(TNF-) were also determined. At 14 to 17 weeks
and 63 weeks, the basal activity and protein expression of eNOS in the
aortas were significantly lower in SHR than in WKY. In addition, the
aged WKY exhibited lower eNOS activity than that of adult WKY, but this
change was not seen in SHR. By comparison, the basal activity and
protein expression of iNOS were only observed in SHR of the
14-to-17-week group and in the 63-week group; SHR still exhibited
higher activities, and these differences were further exaggerated by
treatment with LPS. The basal and LPS-induced
NO2-/NO3- and TNF-
levels in the plasma were also higher in the SHR except the 4-week
group. After treatment with quinapril, the basal and LPS-induced
expressions of iNOS in SHR were significantly attenuated. Our results
demonstrated that alterations of activity and protein expression of
eNOS and iNOS occurred in SHR. In addition, aging may reduce the
activity of eNOS in WKY but not in SHR. The decline of eNOS activity
and/or expression may contribute to the development of hypertension,
whereas the increase of iNOS expression may be a consequence of the
pathological state of vessels associated with hypertension in SHR.
However, the augmented expression of iNOS in SHR was attenuated by
antihypertensive therapy, suggesting that the abnormal expression of
iNOS is associated with hypertension.
Key Words: nitric oxide synthase • hypertension, experimental • rats, inbred SHR
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