perfusion is mainly regulated by the RAAS during hemorrhage, topical application of losartan, a specific antagonist to the AT 1 R, might be a promising concept to improve gastric perfusion at the microvascular level with markedly reduced systemic adverse
Richard Truse, Fabian Voß, Anna Herminghaus, Jan Schulz, Andreas P M Weber, Tabea Mettler-Altmann, Inge Bauer, Olaf Picker, and Christian Vollmer
Tetsuhiro Kakimoto, Kinya Okada, Yoshihiro Hirohashi, Raissa Relator, Mizue Kawai, Taku Iguchi, Keisuke Fujitaka, Masashi Nishio, Tsuyoshi Kato, Atsushi Fukunari, and Hiroyuki Utsumi
application to objectively and rapidly quantify the increase in desmin immunoreactivity in SDT rat glomeruli in the early stages of diabetes. We also examined the ameliorative effect of early treatment with an angiotensin II receptor blocker (ARB), losartan
Bao-Wei Wang, Hang Chang, Peiliang Kuan, and Kou-Gi Shyu
44 MAP kinase. Wortmannin is a potent and specific inhibitor of PI-3 kinase. In experiments involving the AngII receptor antagonist, losartan at 100 nM was added 30 min before AngII stimulation. Western blot analysis Western blot was performed as
Suwattanee Kooptiwut, Wanthanee Hanchang, Namoiy Semprasert, Mutita Junking, Thawornchai Limjindaporn, and Pa-thai Yenchitsomanus
using Annexin V–FITC/propidium iodide staining INS-1 cells were cultured in 11.1 mM or 40 mM glucose in the presence or absence of 1 μM Ang II, with or without 0.05 μg/ml testosterone or 1 μM losartan or a combination of both. After incubation for 72 h
Tusty-Jiuan Hsieh, Pierre Fustier, Chih-Chang Wei, Shao-Ling Zhang, Janos G Filep, Shiow-Shiu Tang, Julie R Ingelfinger, I George Fantus, Pavel Hamet, and John S D Chan
). Losartan (a non-peptide angiotensin II type 1 receptor (AT 1 R) blocker) and perindopril (an angiotensin-converting enzyme (ACE) inhibitor) were gifts from Dr Ronald D Smith (Dupont Merck, Wilmington, DE, USA) and Dr Serge Carrière (Servier Amérique
Hongyu Su, Xueyi Chen, Yueming Zhang, Linglu Qi, Yun He, Juanxiu Lv, Yingying Zhang, Xiang Li, Jiaqi Tang, and Zhice Xu
7. Potassium chloride (0.12 mol/L) was used to measure maximum contractile capability and served as an internal reference. Ang II (10 −11 –10 −5 mol/L) was added in the presence or absence of losartan (10 −5 mol/L) or PD123,319 (10 −5 mol
Hitesh Soni and Adebowale Adebiyi
urantide (20 μg/kg), losartan (1 mg/kg), U-73122 (10 μg/kg), and 2-APB (2 mg/kg) in newborn pigs. Data are expressed as mean± s.e.m. ΔMAP (mmHg) ΔRBF (ml/min) ΔRVR (mmHg/ml per min) ΔCBF (LDF PU) ΔMBF (LDF PU) Urantide *−3.5±0.9 ( n =6) −0.1±0.1 ( n =4
H Kobori, A Ichihara, Y Miyashita, M Hayashi, and T Saruta
It is well known that renal hypertrophy is induced by hyperthyroidism; however, the mechanism is not fully understood. We recently reported that cardiac hypertrophy in hyperthyroidism is mediated by enhanced cardiac expression of renin mRNA. The present study addresses the hypothesis that renal hypertrophy in hyperthyroidism is mediated by amplification of renal expression of renin mRNA. Twenty Sprague-Dawley rats were divided into control (n=5) and hyperthyroid groups by daily intraperitoneal injections of saline vehicle or thyroxine. The hyperthyroid group was subdivided further into hyperthyroid-vehicle (n=5), hyperthyroid-losartan (n=5), and hyperthyroid-nicardipine (n=5) groups by daily intraperitoneal injections of saline vehicle, losartan, or nicardipine. All rats were killed at 4 weeks, and the blood and kidneys were collected. The kidney-to-body weight ratio increased in the hyperthyroid groups (+34%). Radioimmunoassays and reverse transcriptase-polymerase chain reaction revealed increased renal renin (+91%) and angiotensin II (+65%) levels and enhanced renal renin mRNA expression (+113%) in the hyperthyroid groups. Losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced renal hypertrophy. These results suggest that thyroid hormone activates the intrarenal renin-angiotensin system via enhancement of renal renin mRNA expression, which then leads to renal hypertrophy.
J A García-Sáinz, M Martínez-Alfaro, M T Romero-Avila, and C González-Espinosa
In guinea pig hepatocytes angiotensin II induced phosphorylase a activation. This effect was mimicked by other angiotensins with the potency order: angiotensin II (EC50 ≈1 nm)>angiotensin III (EC50 ≈30 nm)>angiotensin I (EC50 ≈300 nm). The effect of 10 nm angiotensin II was blocked by the angiotensin II receptor AT1-selective antagonists irbesartan and losartan (K i values of ≈1 nm and ≈10 nm for irbesartan and losartan respectively) but not by the AT2-selective antagonist PD123177.
Similar data were obtained when the production of [3H]IP3 from [3H]myo-inositol-labeled cells was studied. Angiotensin II induced a dose-dependent increase in [3H]IP3 production; the maximal effect (≈3-fold) was observed at a concentration of 10 μm. This effect of angiotensin II was completely blocked by the AT1-selective antagonists irbesartan and losartan, but only in a very limited fashion by PD123177. [125I][Sar1-Ile8]angiotensin II bound with high affinity (≈3·8 nm) to a moderately abundant number of sites (≈660 fmol/mg protein) in guinea pig liver membranes. Binding competition experiments indicate the following orders of potency for agonists: angiotensin II (≈1·5 nm)>angiotensin III (≈7 nm)>angiotensin I (≈176 nm), and for antagonists: irbesartan (≈0·5 nm)>losartan (≈36 nm)>> PD123177 (>> 10 000 nm).
The functional and binding data strongly indicate that the effects of angiotensin II were mediated through AT1 receptors. Expression of the mRNA for these receptors was confirmed by RT-PCR and hybridization of the reaction product with a radiolabeled rat AT1 receptor cDNA probe.
Journal of Endocrinology (1997) 154, 133–138
ME Fabiani, M Sourial, WG Thomas, CI Johnston, and AG Frauman
The renin-angiotensin system (RAS) is present in the human prostate and may be activated in benign prostatic hyperplasia (BPH), possibly contributing to the pathophysiology of this disorder by enhancing local sympathetic tone and cell growth. The functional role of the RAS in the prostate, however, is unknown. The present study was undertaken to determine whether angiotensin (Ang) II enhances sympathetic transmission in the prostate. The neuronal stores of the rat prostate were labelled with [(3)H]noradrenaline (NA). Ang II and Ang I enhanced [(3)H]NA release in a concentration-dependent manner. The Ang II receptor subtype 1 (AT(1) receptor) antagonist losartan and the AT(2) receptor antagonist PD123319 inhibited this facilitatory effect of Ang II and Ang I, whereas the other AT(2) receptor antagonist, CGP42112, was without effect. Bradykinin also increased [(3)H]NA release, which was inhibited by the B(2) receptor antagonist Hoe140. The angiotensin-converting enzyme inhibitor captopril inhibited the effect of Ang I, but potentiated that of bradykinin. Interestingly, captopril alone produced an increase in [(3)H]NA release which was inhibited by Hoe140. Losartan, but not PD123319 or CGP42112, inhibited [(125)I]-Ang II binding in Chinese hamster ovary cells transfected with the AT(1a) or AT(1b) receptor. In contrast, in cells expressing the AT(2) receptor, PD123319 and CGP42112, but not losartan, inhibited [(125)I]-Ang II binding. In conclusion, Ang II enhances the release of NA from sympathetic nerves of the rat prostate via a novel functional receptor distinct from the cloned AT(1a), AT(1b) or AT(2). These data provide direct evidence in support of a functional role for the local RAS in modulating sympathetic transmission in the prostate, which may have important implications for the pathophysiology of BPH.