angiotensinogen and imidapril

This study examined the association between T1198C polymorphism of the angiotensinogen (AGT) gene and the blood pressure response to ACE inhibitors in a Chinese hypertensive cohort. After a 2-week single-blind placebo run-in period, benazepril (10-20 mg/day) or imidapril (5-10 mg/day) was administered for 6 weeks to 509 patients with mild-to-moderate essential hypertension. Polymerase chain reaction combined with restriction enzyme digestion was used to detect the polymorphism, and the patients were classified as having the TT, TC, or CC genotype. The achieved changes in systolic and diastolic blood pressure (SBP and DBP) were analyzed to determine their association with genotypes at the AGT gene locus. In the total 509 patients, the TT genotype was observed in 44 patients (8.7%), the TC genotype in 214 patients (42.0%), and the CC genotype in 251 patients (49.3%). The SBP reductions in patients with the TT genotype, TC genotype, and CC genotype were -15.3+/-12.7 mmHg, -14.0+/-12.7 mmHg, and -14.4+/-12.4 mmHg, respectively (p=0.809). The DBP reductions in patients with the TT genotype, TC genotype, and CC genotype were -8.5+/-8.1 mmHg, -8.3+/-7.5 mmHg, and -8.9+/-6.6 mmHg, respectively (p=0.638). There were no significant differences in the changes in SBP or DBP after treatment among the three genotype groups. In conclusion, these results suggest that the AGT genotype does not predict the blood pressure-lowering response to antihypertensive treatment with ACE inhibitors in Chinese hypertensive patients.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Antihypertensive Agents; Benzazepines; Blood Pressure; China; Double-Blind Method; Female; Humans; Hypertension; Imidazolidines; Male; Middle Aged; Polymorphism, Genetic

It has been suggested that proangiotensin-12 (proang-12), a novel angiotensin peptide recently discovered in rat tissues, may function as a component of the tissue renin-angiotensin system (RAS). To investigate the role of proang-12 in the production of angiotensin II (Ang II), we measured its plasma and tissue concentrations in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, with and without RAS inhibition. The 15-week-old male WKY and SHR rats were left untreated or were treated for 7 days with 30 mg kg(-1) per day losartan, an angiotensin receptor blocker, or with 20 mg kg(-1) per day imidapril, an angiotensin-converting enzyme (ACE) inhibitor. Both treatments increased renin activity and the concentrations of angiotensin I (Ang I) and Ang II in the plasma of WKY and SHR rats, but neither affected plasma proang-12 levels. In contrast to the comparatively low level of proang-12 seen in plasma, cardiac and renal levels of proang-12 were higher than those of Ang I and Ang II. In addition, despite activation of the RAS in the systemic circulation, tissue concentrations of proang-12 were significantly reduced following treatment with losartan or imidapril. Similar reductions were also observed in the tissue concentrations of Ang II in both strains, without a reduction in Ang I. These results suggest that tissue concentrations of proang-12 and Ang II are regulated independently of the systemic RAS in WKY and SHR rats, which is consistent with the notion that proang-12 is a component of only the tissue RAS.

Topics: Angiotensin I; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Animals; Blood Pressure; Body Weight; Imidazolidines; Kidney; Losartan; Male; Myocardium; Organ Size; Peptide Fragments; Radioimmunoassay; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renin; Renin-Angiotensin System

Effects of isoproterenol (ISO) on the expression of cardiac angiotensinogen mRNA, angiotensin converting enzyme (ACE) activity, and mechanical functions in spontaneously hypertensive rats were investigated. In the acute phase, defined as within 24 h after the subcutaneous injection of ISO 85 mg/kg, cardiac angiotensinogen mRNA was slightly induced, but ACE activity was not. In the subacute phase, defined as within 8 d after ISO treatment on 2 successive d, both angiotensinogen mRNA expression and ACE activity in the heart were markedly induced. ACE activity in serum was not affected by ISO in either phase. In the subacute phase, ISO reduced body weight and blood pressure, increased ventricular weight and calcium content, and impaired cardiac mechanical function. Oral treatment with imidapril (10 mg/kg/d), an ACE inhibitor, 1 h before each ISO treatment and on the following 6 d, improved ventricular hypertrophy, the elevation of the left ventricular end diastolic pressure, the reduction in contractility, and the prolongation of the time constant. Imidapril significantly suppressed both serum and cardiac ACE activity but did not affect cardiac angiotensinogen mRNA expression in the subacute phase. These results indicate that enhancement of cardiac angiotensinogen mRNA and ACE activity is involved in ISO-induced cardiac dysfunction. Imidapril improved ISO-induced cardiac dysfunction, possibly by suppression of the local ACE activity as well as circulating ACE activity.

Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Animals; Blood Pressure; Body Weight; Cardiotonic Agents; Heart Rate; Hypertension; Imidazoles; Imidazolidines; Isoproterenol; Myocardium; Peptidyl-Dipeptidase A; Rats; Rats, Inbred SHR; RNA, Messenger