Non-alcoholic fatty liver disease and portal hypertension
Nizar Zein, Bret Lashner in The Year in Gastroenterology and Hepatology, 2005
(25 mg) of losartan to propranolol (40 mg twice daily, with further titration based on pulse rate changes). The impact of these agents on portal pressure 14 days after initiation of therapy was the principle end-point. Table 17.3 identifies changes in haemodynamics for each drug. Bleeding rates were also measured. Baseline hepatic and haemodynamic findings in the two groups were comparable. Each drug caused a significant reduction in wedged hepatic pressure gradient. In neither group was there a significant reduction in systemic blood pressure. Reductions in wedged hepatic vein pressure gradient below 12 mmHg (a level at which variceal haemorrhage risk disappears) was equally likely in each group (35-42%).There were no significant side effects in either group. Losartan may have been more effective than propranolol in those who had ascites. It also appeared to be more
Renal, Cardiovascular, and Pulmonary Functions of Dopamine
Nira Ben-Jonathan in Dopamine, 2020
The antihypertensive effect of DA in the kidney is also exemplified by its interactions with losartan, a nonpeptide angiotensin II receptor antagonist with high affinity and selectivity for the AT1 receptor. Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by inhibiting its binding to the AT1 receptor. In cultured rat proximal tubule cells that express endogenous AT1R and D1R, losartan causes D1R activation [18]. Moreover, administration of a D1R antagonist to rats with renal hypertension significantly attenuates the antihypertensive effect of losartan. These data indicate that losartan exerts its strong antihypertensive effects by inhibiting AT1R signaling, and this is reinforced by the enhancement of D1R signaling.
Practice Paper 4: Answers
Anthony B. Starr, Hiruni Jayasena, David Capewell, Saran Shantikumar in Get ahead! Medicine, 2016
Losartan is an angiotensin II receptor antagonist. In health, the activation of angiotensin II receptors by angiotensin II results in peripheral vasoconstriction, stimulation of aldosterone release, and reabsorption of sodium and water from the renal tubules. Inhibition of these actions by angiotensin II receptor antagonists helps reduce blood pressure in hypertensive patients. They are usually used as second-line agents in patients who are intolerant to the side effects of angiotensin-converting enzyme (ACE) inhibitors, e.g. ramipril.
Increased levels of angiotensin II type 1 receptor autoantibodies in female infertility
Published in Systems Biology in Reproductive Medicine, 2021
Fang Liu, Guifang Yang, Ruixia Guo, Li Xue, Lijuan Wang, Jingjing Guo, Xiaoli Yang
AT1-AA plays a role in infertility. Prevention and treatment of its pathological role may improve the outcome of infertility, e.g., the use of AT1R blocker. Studies have shown that the use of AT1R antagonist losartan can improve follicular development in obese women (Wallukat et al. 1999), but other studies have suggested that the use of AT1R antagonist in late pregnancy puts offspring at risk of kidney damage (Griendling et al. 2000), which may cause side effects during use. It is necessary to develop effective and safe blockers of AT1-AA. However, by examining epidemiological factors leading to high levels of AT1-AA in infertile women their reduction may effectively prevent and improve the level of AT1-AA in women of childbearing age. Logistic regression analysis was conducted to further analyze such factors as age, BMI, type of infertility, infertile years, adverse pregnancy history, fallopian tube condition, and polycystic ovary syndrome. The results showed that none of the above factors affected the in vivo level of AT1-AA in infertile patients. It is suggested that the production of AT1-AA and the possible effect of oocyte maturation disorder are closely related to individual differences. However, the response of age to ovarian function is an important factor, and the age of the subjects in this study is relatively concentrated, so it does not reflect this phenomenon very well.
Protective effects of combined Losartan and Nilotinib on carbon tetrachloride (CCl4)-induced liver fibrosis in rats
Published in Drug and Chemical Toxicology, 2020
Jamshid Karimi, Adel Mohammadalipour, Nasrin Sheikh, Iraj Khodadadi, Mohammad Hashemnia, Farjam Goudarzi, Vahid Khanjarsim, Ghasem Solgi, Mehrdad Hajilooi, Majid Bahabadi, Nejat Kheiripour, Keshvad Hedayatyanfard
Twelve weeks’ intoxication of CCl4 showed weakness, emaciation, and fatigue in the rats. The serum parameters changes due to intoxication of CCl4 recorded by a significant increase in ALT, AST, and ALP activities along with an increase in total bilirubin above the normal limit of control groups (p < 0.001, versus Groups N, O, NN10, NL10). These high levels were declined gradually in rats treated with Losartan, Nilotinib and their combination (p < 0.01 versus Group F). Although the effect of combined treatment was not superior compared with single agent to normalize ALP and BilT, but the more beneficial effects of combined treatment was evidenced by remarkable attenuation of ALT (p < 0.001, versus Group FL10) and AST activity (p < 0.001, versus Group FL10, p < 0.01, versus Group FN10). The mediocre of CCl4 intoxication was further reconfirmed by a significant reduction in weight gain within 12 weeks (p < 0.001, versus groups N, O, NN10, NL10). Interestingly, significant weight gain was seen in Nilotinib (p < 0.01 versus Group F), Losartan (p < 0.05 versus Group F) and their combined treatment (p < 0.001 versus Group F) (Table 1).
Effects of quercetin on the pharmacokinetics of losartan and its metabolite EXP3174 in rats
Published in Xenobiotica, 2019
Qingling Zhao, Jinlan Wei, Hongying Zhang
Losartan is the first non-peptide angiotensin II receptor blocker used for the treatment of hypertension (Klishadi et al., 2015). After oral administration, losartan can be absorbed quickly and transformed into its active metabolite EXP3174 mediated by cytochrome P450 enzymes CYP3A4 and CYP2C9, and EXP3174 is about 10-fold more potent than its parent drug (Rincon et al., 2015). Losartan is also a substrate of P-glycoprotein (P-gp) (Yang et al., 2011b). Losartan has been one of the anti-hypertension drug most frequently used for the prevention and control of hypertension in the clinic because of its good anti-hypertension effect (Yang et al., 2011a; Yasar et al., 2008). Considering that losartan is a substrate of both CYP enzymes and P-gp, modulation of CYP and P-gp activities may cause significant changes in the pharmacokinetic profiles of losartan and its active metabolite EXP3174 (Kobayashi et al, 2008; Yuan et al., 2013; Zaidenstein et al., 2001).
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