From the First Department of Internal Medicine, Faculty of Medicine,
Kyushu University, Fukuoka (S.O., Y.N.), and the Department of Bioclimatology
and Medicine, Medical Institute of Bioregulation, Kyushu University, Oita
(M.S., N.M., S.S., T.H.), Japan.
Correspondence to M. Sugano, MD, Department of Bioclimatology and Medicine, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, Oita 874-0838, Japan.
Abstract—We administered
angiotensin II (Ang II) receptor type 1 (AT1)
blockade (losartan, 40 mg · kg-1 ·
d-1), type II receptor (AT2) blockade
(PD123319, 100 mg · kg-1 ·
d-1), or angiotensin-converting enzyme (ACE)
inhibitor (enalapril, 30 mg · kg-1
· d-1) to spontaneously hypertensive rats (SHR) from 10
to 20 weeks of age. Control SHR and Wister-Kyoto rats (WKY) received a
placebo for the same period. At the end of treatment, losartan
and enalapril were both found to have significantly reduced the
arterial systolic blood pressure and the collagen
concentration to the level of WKY, whereas PD123319 had no effect.
Enalapril and PD123319 significantly reduced the media cross-sectional
area of the aorta in comparison to that of untreated SHR, which was
still larger than that of the WKY; however, losartan did not
change it. Using reverse transcription–polymerase chain reaction, we
next examined the mRNA expressions for ACE, AT1 receptor,
and AT2 receptor in experimental animals. We observed
significantly enhanced mRNA expression for AT1 and
AT2 receptors and ACE in untreated SHR compared with WKY.
The AT1 mRNA level was also significantly decreased in the
SHR treated with either losartan or enalapril, whereas the
AT2 mRNA level was significantly decreased in the SHR
treated with either PD123319 or enalapril in comparison to untreated
SHR. The level of ACE mRNA was significantly decreased only in the SHR
treated with enalapril. These results indicate that AT1
receptor, but not AT2 receptor, plays a crucial role in the
remodeling of matrix tissue, while AT2 receptor may play a
role in the development of hypertrophy of smooth muscle in
aorta in SHR, and that the reduction of hypertrophy of
smooth muscle does not fully account for the suppression of
hypertension.
© 1998 American Heart Association, Inc.
Scientific Contributions
Interaction of mRNAs for Angiotensin II Type 1 and Type 2 Receptors to Vascular Remodeling in Spontaneously Hypertensive Rats
Key Words: angiotensin II • receptors, angiotensin • hypertrophy, vascular • collagen • rats, inbred SHR
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