Disease relevance of candesartan

• The number of candesartan responders (reduction of > or =50% compared with placebo) was 18 (31.6%) of 57 for days with headache and 23 (40.4%) of 57 for days with migraine [1].
• Treatment with a selective AT1 antagonist, CV-11974, before ischemia blocked reperfusion arrhythmias in wild-type mice but had no effects on infarct size [2].
• We p.o. administered the long-acting AT1R antagonist, candesartan (10 mg/kg), to the 16 days mouse renal cancer lung metastasis model to test the preventive effects in tumor metastasis [3].
• Candesartan is widely used clinically, so it seems to be a reasonable therapy for patients with lung metastases of renal cell carcinoma [3].
• METHODS: We administered placebo or candesartan 16 mg daily during two months to 45 patients with mild-to-moderate hypertension [4].

Psychiatry related information on candesartan

• A first major cardiovascular event occurred in 242 candesartan patients and in 268 control patients; risk reduction with candesartan was 10.9% [95% confidence interval (CI), -6.0 to 25.1, P = 0.19] [5].
• OBJECTIVE: To assess whether candesartan-based antihypertensive treatment in elderly patients with mildly to moderately elevated blood pressure confers a reduction in cardiovascular events, cognitive decline and dementia [5].
• Candesartan did not alter feeding behavior or circulatory response to feeding [6].
• Blood pressure was reduced from 162.1/91.1 to 140.1/78.9 mmHg in the candesartan group and from 165.9/95.9 to 138.4/81.1 mmHg in the conventional therapy group [7].

High impact information on candesartan

• All of these events are inhibited by the AT1 receptor blocker candesartan [8].
• Neither swallow-induced axial movements, nor the contraction after transient lower esophageal sphincter relaxations, were influenced by candesartan pretreatment [9].
• Administration of the AT(1) receptor antagonist candesartan reduced the amplitude of swallow-induced peristaltic contractions and both the length and pressure amplitude of baseline high-pressure zone at the esophagogastric junction [9].
• Neither an angiotensin-II type 1 (AT1) receptor antagonist, CV-11974, nor angiotensin-I affected beta-AR density [10].
• In an isolated perfused rat heart preparation, infusion of bosentan (1 micromol/L) for 2 hours inhibited the mechanical stretch-induced increase in BNP mRNA levels in the right atria, whereas an AT1 receptor antagonist, CV-11974 (10 nmol/L), had no effect [11].

Chemical compound and disease context of candesartan

• Stroke prevention with the angiotensin II type 1-receptor blocker candesartan in elderly patients with isolated systolic hypertension: the Study on Cognition and Prognosis in the Elderly (SCOPE) [12].
• When a washout period was implemented between pretreatment and ischemia, the protective effect of candesartan, but not that of losartan, remained, suggesting that candesartan may provide a more efficient cardioprotection than losartan [13].
• Pioglitazone reduced proteinuria as effectively as candesartan and limited renal functional and structural changes [14].
• OBJECTIVE: To assess and compare the long-term effects of the combination of candesartan and lisinopril with high-dose lisinopril on systolic blood pressure in patients with hypertension and diabetes [15].
• Comparative impact of enalapril, candesartan or metoprolol alone or in combination on ventricular remodelling in patients with congestive heart failure [16].

Biological context of candesartan

• Pretreatment of cultured cardiomyocytes with 10(-7) mol/L CV-11974 inhibited an increase in [3H]phenylalanine incorporation, MAP kinase activity, and c-fos gene expression induced by stretch of cardiomyocytes [17].
• CONCLUSIONS: In elderly patients with ISH, antihypertensive treatment based on the ARB candesartan resulted in a significant 42% RR reduction in stroke in comparison with other antihypertensive treatment, despite little difference in blood pressure reduction [12].
• The candesartan IC50 values for percentage changes in renal blood flow did not differ in the two groups of mice [18].
• The lower candesartan dose, which did not cause hypotension, elicited substantial increases in RBF and proportionally much greater increases in sodium excretion, revealing the direct renal vasodilation and natriuretic effects of AT1 receptor blockade [19].
• The effects of AngII on IL-6 release and gene expression were completely blocked by the AngII receptor type 1 (AT1 receptor) antagonist CV-11974 [20].

Anatomical context of candesartan

• Stretching cardiac myocytes increased amino acid incorporation, which was also inhibited by approximately 70% with the pretreatment by saralasin or CV-11974 [21].
• In conclusion, candesartan exerts a cardioprotective effect, via a local mechanism within the ischemic myocardium [13].
• Candesartan was administered into the renal artery of nonclipped kidneys to avoid the confounding consequences of decreases in arterial pressure [22].
• The aldosterone-releasing activity of adipocytes was not inhibited by candesartan [23].
• METHODS: Sustained AF was induced in 20 dogs (10 in a control group and 10 in a candesartan group) by rapid pacing of the right atrium (RA) at 400 beats/min for five weeks [24].

Associations of candesartan with other chemical compounds

• Recent studies with normal rats indicated that systemic administration of the angiotensin II (AngII) type 1 (AT1) receptor blocker candesartan elicited divergent renal hemodynamic and excretory responses depending on the magnitude of associated decreases in mean arterial pressure [19].
• Neither losartan (1 microM) nor candesartan (1 nM) significantly affected basal NO production, but both of these AT1-receptor blockers markedly blunted NO release in response to AngII (10 nM): 77+/-6% inhibition with losartan (n=8) and 63+/-9% with candesartan (n=8) [25].
• In contrast, dorsal root ganglia AT1 receptor mRNA content was significantly decreased in RRM (0.52+/-0.06) compared with sham-operated rats (1.18+/-0.07), and this decrease was abolished by ramipril (1.40+/-0.13) and candesartan treatment (1.56+/-0.11) [26].
• A combination of candesartan, felodipine, and the lipid peroxidation inhibitor H290/51 produced a more pronounced infarct limitation than each of these agents alone [13].
• It is interesting that both glomerular cell number and glomerulosclerosis were significantly decreased by candesartan and normalized by the addition of probucol [27].

Gene context of candesartan

• Candesartan effectively blocks AT1A and AT1B receptors in renal resistance vessels of rodents, with similar efficacies in rats and mice [18].
• Administration of candesartan into SKOV-3-transplanted athymic mice resulted in the reduction of peritoneal dissemination, decreased ascitic VEGF concentration, and suppression of tumor angiogenesis [28].
• Furthermore, candesartan decreased renal tissue Ang II contents (from 216 +/- 19 to 46 +/- 3 fmol/mL) and ERK1/2, JNK, and BMK1 activities (-45%, -60%, and -70%, respectively) in DS/H rats [29].
• Both candesartan and neutralizing antibody against TGF-beta completely prevented AGEs-induced Smad2 phosphorylation and TGF-beta-inducible promoter activity [30].
• Furthermore, treatment with candesartan diminished JNK1 activity and downregulated SMAD2 protein and activity in obstructed kidneys [31].

Analytical, diagnostic and therapeutic context of candesartan

• RESULTS: Of the ISH patients, 754 were randomized to the candesartan group and 764 to the control group [12].
• To evaluate the responses to candesartan in hypertensive rats, experiments were performed 25 d after unilateral renal arterial constriction with a 0.25-mm clip [19].
• Injections of AngII caused dose-related increases in systemic arterial and in hindquarters perfusion pressure that were reduced by candesartan [32].
• Blockade of AT1 receptors was achieved by intravenous injection of 0.05 mg/kg candesartan, which did not affect mean arterial pressure [33].
• The hypertensive rats were randomized to no treatment (n = 8) or treatment with the angiotensin type 1 receptor (AT1R) antagonist candesartan (1 mg/kg per day, n = 10) after the baseline echocardiography study [34].

References