MOLECULAR MECHANISM OF ANGIOTENSIN-II TYPE-I AND TYPE-II RECEPTORS INCARDIAC-HYPERTROPHY OF SPONTANEOUSLY HYPERTENSIVE RATS

We administered angiotensin (Aug) II receptor type 1 (AT(1)) blockade (losartan; 10 or 40 mg/kg per day), type IT receptor (AT(1)) blockades (PD123319; 100 mg/kg per day), or angiotensin-converting enzyme (ACE) inhibitor (enalapril; 30 mg/kg per day) to spontaneously hypertensive rats (SHR) from 10 to 20 weeks of age. At the end of the treatment, h igh doses of losartan and enalapril significantly reduced the arterial systolic blood pressure compared with the untreated SHR to the level of WKY rats. But low doses of losartan and PD123319 were without effec t. High doses of losartan and enalapril also significantly reduced bot h the left ventricular (LV) weight and the ratio of LV to body weight compared with the untreated SHR, which were still larger than that of WKY rats. However, the collagen concentration of SHR treated with high doses of losartan or enalapril was completely reduced to the level of WKY rats. Using reverse transcription polymerase chain reaction, we e xamined the mRNA expression for ACE, AT(1), and AT(2) in experimental animals. The enhanced AT(1) mRNA expression was significantly decrease d in the SHR treated with a high dose of losartan or PD123319 compared with the untreated SHR. The level of ACE mRNA was also decreased in t he SHR treated with a high dose of losartan or enalapril. The level of AT(2) mRNA was nor significantly different between the Wistar-Kyoto r ats and the SHR; however, this expression was decreased significantly after the treatment with a high dose of losartan or PD123319. These re sults indicate that AT(1) receptor and ACE, but not AT(2) receptor, pl ay a crucial role in the remodeling of matrix tissue but a smaller rol e in the development of the hypertrophy of LV myocyte in SHR and that the LV/body weight changes do not fully account for the complete suppr ession of hypertension.