leptin and candesartan

The present study was designed to determine the effect of different doses of the angiotensin II receptor blocker (ARB), candesartan, on circulating adiponectin and leptin levels as well as leptin adiponectin ratio (LAR) in hypertensive patients with multiple cardiovascular risk factors.Sixty-nine hypertensive patients were randomized to three groups: group 1 included patients treated with high doses of Candesartan (32 mg); group 2 included patients treated with conventional doses of Candesartan (16 mg); and group 3 included patients that received antihypertensive treatment other than ARBs or angiotensin-converting-enzyme inhibitors. Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, c-reactive protein, aldosterone, renin, Homeostasis model assessment-insulin resistance, leptin, adiponectin and LAR. Baseline adiponectin, leptin, and LAR levels did not differ significantly between the three groups. After 6 months of treatment, LAR was significantly higher in group 3 than group 1 (P = .007) or group 2 (P = .023). Differences between effects of high (32 mg) and conventional doses (16 mg) of Candesartan on LAR were not observed (P = .678). Marginal across-group differences were detected for posttreatment circulating adiponectin level (P = .064). Univariate general linear model (GLM) analysis of posttreatment LAR detected significant by-group differences even after adjustment for age, gender, baseline values of LAR, and blood pressure. In this model, group was the only significant predictor of LAR after controlling for these variables. Treatment with high doses of the ARB, candesartan, is associated with significantly reduced LAR and marginally increased circulating adiponectin levels in hypertensive patients with multiple cardiovascular risk factors.

Topics: Adipokines; Adiponectin; Angiotensin Receptor Antagonists; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Cardiovascular Physiological Phenomena; Female; Homeostasis; Humans; Hypertension; Leptin; Male; Middle Aged; Renin-Angiotensin System; Tetrazoles

[Figure: see text].

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensins; Benzimidazoles; Biphenyl Compounds; Female; Humans; Leptin; Leucyl Aminopeptidase; Placenta; Pre-Eclampsia; Pregnancy; Renin-Angiotensin System; Tetrazoles; Uterine Artery; Vascular Resistance

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Benzoates; Biphenyl Compounds; Cell Line; Dose-Response Relationship, Drug; Glucagon; Hypoglycemic Agents; Islets of Langerhans; Leptin; Male; Mice, Inbred C57BL; Rats, Sprague-Dawley; Rats, Zucker; Receptor, Angiotensin, Type 1; Telmisartan; Tetrazoles; Time Factors; Up-Regulation

AT(1)-blockade has been shown to induce weight loss in animals or patients. The aim of this study was to investigate whether weight reduction after AT(1)-blockade is dependent on dose, blood pressure reduction and leptin signalling. Spontaneously hypertensive rats (SHR) and lean and obese Zucker rats were treated for 4 weeks with candesartan (0, 2, 6 or 16 mg/kg/day). Body weight, food intake and hypothalamic mRNA levels of (an)orexigenic peptides were determined. Obese Zucker rats served as a model of primary leptin resistance. In SHR, body mass index and food intake were decreased selectively by 16 mg/kg/day candesartan but not after using normal (2 mg/kg/day) or supranormal (6 mg/kg/day) doses. Correlation analysis between blood pressure and body weight indicated no relationship of hypotensive potency on weight loss. The hypothalamic mRNA levels of the orexigenic peptide MCH (melanin-concentrating hormone) were diminished in parallel. Consistent to the results in SHRs, 16 mg/kg/day candesartan revealed a decrease of body weight, food intake and hypothalamic MCH mRNA levels in lean Zucker rats. In obese Zucker rats, none of these parameters were reduced by candesartan. Loss of body weight and hypophagia are not general features of AT(1)-blockers, since neither was seen after normal or moderately supranormal doses, but they were, after the highest doses. These actions of AT(1)-blockers occur independently of their ability to lower blood pressure. They do depend on an intact leptin signalling, since they were absent in obese Zucker rats that feature a genetic mutation of the leptin receptor.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Dose-Response Relationship, Drug; Eating; Hypothalamus; Leptin; Male; Obesity; Rats; Rats, Inbred SHR; Rats, Zucker; Receptors, Leptin; RNA, Messenger; Signal Transduction; Tetrazoles; Weight Loss

The fat cell hormone leptin is known to be implicated in the pathogenesis of hypertension and cardiovascular disease. Here we tested whether angiotensin (Ang) II is involved in the control of leptin release from human adipocytes.. Leptin secretion was assessed from in vitro differentiated human adipocytes by radioimmunoassay. Western blot experiments were used to test for the signaling pathway activated by Ang II.. Ang II increased leptin secretion into the culture medium in a dose- and time-dependent fashion. At 10(-5) M Ang II, the leptin concentration in the medium was increased at 24 hours by 500+/-222% compared with control cultures (p<0.05). This effect was also seen at the mRNA level. Similar effects were seen after exposure of fat cells to Ang III and Ang IV. Preincubation of fat cells with candesartan, an angiotensin II type 1 receptor antagonist, or the extracellular-signal-regulated kinases 1 and 2 inhibitor UO126 completely abolished the effect of Ang II on leptin production. The peroxisome proliferator-activated receptor-gamma agonist troglitazone modestly attenuated leptin release.. In conclusion, Ang II and its metabolites stimulated leptin production in human adipocytes. This effect is mediated through an extracellular-signal-regulated kinases 1 and 2-dependent pathway and includes the angiotensin II type 1 receptor subtype.

Topics: Adipocytes; Adult; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl Compounds; Blotting, Western; Butadienes; Cells, Cultured; Chromans; Drug Interactions; Extracellular Signal-Regulated MAP Kinases; Female; Fibrinolytic Agents; Humans; Leptin; MAP Kinase Signaling System; Nitriles; Protein Kinase Inhibitors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tetrazoles; Thiazolidinediones; Troglitazone