In spontaneously hypertensive rats, AT1 receptor blockade and ACE inhibition reduced systolic blood pressure and collagen concentration, whereas AT2 blockade had no effect.
Does AT1 blockade, AT2 blockade, or ACE inhibition improve vascular remodeling and hypertension in spontaneously hypertensive rats?
AT1 receptor plays a crucial role in matrix tissue remodeling, while AT2 receptor may play a role in smooth muscle hypertrophy development in the aorta of spontaneously hypertensive rats.
We administered angiotensin II (Ang II) receptor type 1 (AT1) blockade (losartan, 40 mg x kg-1 x d-1), type II receptor (AT2) blockade (PD123319, 100 mg x kg-1 x d-1), or angiotensin-converting enzyme (ACE) inhibitor (enalapril, 30 mg x kg-1 x 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.
Otsuka et al. (Tue,) conducted a other in Hypertension. Losartan, PD123319, or enalapril vs. Placebo was evaluated on Arterial systolic blood pressure, collagen concentration, media cross-sectional area of the aorta, and mRNA expressions. In spontaneously hypertensive rats, AT1 receptor blockade and ACE inhibition reduced systolic blood pressure and collagen concentration, whereas AT2 blockade had no effect.