Browsing by Subject "Losartan"

Now showing 1 - 3 of 3
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    Angiotensin-II is a putative neurotransmitter in lactate-induced panic-like responses in rats with disruption of GABAergic inhibition in the dorsomedial hypothalamus
    (Society for Neuroscience, 2006-09-06) Shekhar, Anantha; Johnson, Philip L.; Sajdyk, Tammy J.; Fitz, Stephanie D.; Keim, Stanley R.; Kelley, Pamela E.; Gehlert, Donald R.; DiMicco, Joseph A.; Psychiatry, School of Medicine
    Intravenous sodium lactate infusions or the noradrenergic agent yohimbine reliably induce panic attacks in humans with panic disorder but not in healthy controls. However, the exact mechanism of lactate eliciting a panic attack is still unknown. In rats with chronic disruption of GABA-mediated inhibition in the dorsomedial hypothalamus (DMH), achieved by chronic microinfusion of the glutamic acid decarboxylase inhibitor L-allylglycine, sodium lactate infusions or yohimbine elicits panic-like responses (i.e., anxiety, tachycardia, hypertension, and tachypnea). In the present study, previous injections of the angiotensin-II (A-II) type 1 receptor antagonist losartan and the nonspecific A-II receptor antagonist saralasin into the DMH of "panic-prone" rats blocked the anxiety-like and physiological components of lactate-induced panic-like responses. In addition, direct injections of A-II into the DMH of these panic-prone rats also elicited panic-like responses that were blocked by pretreatment with saralasin. Microinjections of saralasin into the DMH did not block the panic-like responses elicited by intravenous infusions of the noradrenergic agent yohimbine or by direct injections of NMDA into the DMH. The presence of the A-II type 1 receptors in the region of the DMH was demonstrated using immunohistochemistry. Thus, these results implicate A-II pathways and the A-II receptors in the hypothalamus as putative substrates for sodium lactate-induced panic-like responses in vulnerable subjects.
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    The Effects of Amlodipine Compared to Losartan in Patients With Mild to Moderately Severe Hypertension
    (Wiley, 2003) Phillips, Robert A.; Kloner, Robert A.; Grimm, Richard H., Jr.; Weinberger, Myron; Medicine, School of Medicine
    The calcium channel blocker amlodipine and angiotensin II receptor blocker losartan, with or without hydrochlorothiazide (HCTZ), were compared for the treatment of mild to moderate hypertension in a multicenter, double-blind, parallel-group clinical trial. Following a 2-week placebo run-in, 440 adults (45-80 years old) were randomized to receive either amlodipine 5 mg once daily or losartan 50 mg once daily. Patients who failed to meet the sitting diastolic blood pressure (BP) reduction goal of
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    Randomized placebo-controlled trial of losartan for pediatric NAFLD
    (Wiley, 2022) Vos, Miriam B.; Van Natta, Mark L.; Blondet, Niviann M.; Dasarathy, Srinivasan; Fishbein, Mark; Hertel, Paula; Jain, Ajay K.; Karpen, Saul J.; Lavine, Joel E.; Mohammad, Saeed; Miriel, Laura A.; Molleston, Jean P.; Mouzaki, Marialena; Sanyal, Arun; Sharkey, Emily P.; Schwimmer, Jeffrey B.; Tonascia, James; Wilson, Laura A.; Xanthakos, Stavra A.; NASH Clinical Research Network; Pediatrics, School of Medicine
    Background and aims: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects. Approach and results: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT levels from baseline to 24 weeks, and the preset sample size was n = 110. Treatment effects were assessed using linear regression of change in treatment group adjusted for baseline value. Eighty-three participants (81% male, 80% Hispanic) were randomized to losartan (n = 43) or placebo (n = 40). During an enrollment pause, necessitated by the 2019 coronavirus pandemic, an unplanned interim analysis showed low probability (7%) of significant group difference. The Data and Safety Monitoring Board recommended early study termination. Baseline characteristics were similar between groups. The 24-week change in ALT did not differ significantly between losartan versus placebo groups (adjusted mean difference: 1.1 U/l; 95% CI = -30.6, 32.7; p = 0.95), although alkaline phosphatase decreased significantly in the losartan group (adjusted mean difference: -23.4 U/l; 95% CI = -41.5, -5.3; p = 0.01). Systolic blood pressure decreased in the losartan group but increased in placebo (adjusted mean difference: -7.5 mm Hg; 95% CI = -12.2, -2.8; p = 0.002). Compliance by pill counts and numbers and types of adverse events did not differ by group. Conclusions: Losartan did not significantly reduce ALT in children with NAFLD when compared with placebo.