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Renal, Cardiovascular, and Pulmonary Functions of Dopamine
Published in Nira Ben-Jonathan, 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.
Allergy
Published in Keith Hopcroft, Instant Wisdom for GPs, 2017
Tak Chin, Elizabeth Griffiths, S. Hasan Arshad
The mechanism of ACE-induced angioedema is not allergic. While it is an easy diagnosis to pick up when ACE inhibitors have just been started, ACE-induced angioedema more often occurs after many years of uneventful use. As a result, many patients have recurrent episodes of orofacial angioedema before the diagnosis is made. Angiotensin-II receptor antagonists, such as losartan, are considered safe to use in these patients.
Practice Paper 4: Answers
Published in Anthony B. Starr, Hiruni Jayasena, David Capewell, Saran Shantikumar, Get ahead! Medicine, 2016
Anthony B. Starr, Hiruni Jayasena, David Capewell
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.
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).
Losartan/hydrochlorothiazide combination is safe and effective for morning hypertension in Very-Elderly patients
Published in Clinical and Experimental Hypertension, 2018
Hiroki Uchiwa, Hisashi Kai, Yoshiko Iwamoto, Takahiro Anegawa, Hidemi Kajimoto, Kenji Fukuda, Tsutomu Imaizumi, Yoshihiro Fukumoto
There were several limitations for the current study. First, there were only a small number of patients in each group, as this was a subanalysis of our previous MAPPY study. Therefore, we need to be careful in interpreting the results of the present study owing to the low statistical power of the analysis. Second, high-dose losartan was only administered once every morning in the current study. It is possible that the administration of high-dose losartan would be more effective for controlling morning hypertension if it was administered once in the evening or if the dose was halved and then administered both in the morning and in the evening. This issue will be addressed in a future study. Third, the majority of the patients enrolled in this study were not observed during the summer season. Thus, we cannot deny the possibility that there would be an increased prevalence of adverse effects for the combination therapy during the summer, such as dehydration, fainting, symptomatic hypotension, and renal dysfunction. Finally, a further randomized study with a larger patient number and longer observation period should be undertaken in order to determine the long-term safety and efficacy of the losartan/HCTZ combination therapy for cardiovascular morbidity and mortality in Very-Elderly patients.