Candesartan Cilexetil: An Angiotensin II Receptor Blocker

Stoukides, Cheryl A.; McVoy, Heather J; Kaul, Alan F.

doi:10.1345/aph.19005

Cited by 13 publications

(13 citation statements)

References 42 publications

(39 reference statements)

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“…This response was completely blocked by the potent AT1 receptor antagonist candesartan CV-11974 (1 µmol/l) (75,76). In contrast, stretch-induced KDR expression was not significantly inhibited by candesartan (Fig.…”

Section: Suzuma and Associatesmentioning

confidence: 96%

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Cyclic Stretch and Hypertension Induce Retinal Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor—2

et al. 2001

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A single exposure to 20% symmetric static stretch increased KDR mRNA expression 3.9 ± 1.1-fold after 3 h (P = 0.002), with a gradual return to baseline within 9 h. In contrast, BRECs exposed to cardiac-profile cyclic stretch at 60 cpm continuously accumulated KDR mRNA in a transcriptionally mediated, time-dependent and stretchmagnitude-dependent manner. Exposure to 9% cyclic stretch increased KDR mRNA expression 8.7 ± 2.9-fold (P = 0.011) after 9 h and KDR protein concentration 1.8 ± 0.3-fold (P = 0.005) after 12 h. Stretched-induced VEGF responses were similar. Scatchard binding analysis demonstrated a 180 ± 40% (P = 0.032) increase in high-affinity VEGF receptor number with no change in affinity. Cyclic stretch increased basal thymidine uptake 60 ± 10% (P < 0.001) and VEGF-stimulated thymidine uptake by 2.6 ± 0.2-fold (P = 0.005). VEGFNAb reduced cyclic stretch-induced thymidine uptake by 65%. Stretched-induced KDR expression was not inhibited by AT1 receptor blockade using candesartan. Hypertension increased retinal KDR expression 67 ± 42% (P < 0.05) in SHR rats compared with normotensive WKY control animals. When hypertension was reduced using captopril or candesartan, retinal KDR expression returned to baseline levels. VEGF reacted similarly, but Flt expression did not change. These data suggest a novel molecular mechanism that would account for the exacerbation of diabetic retinopathy by concomitant hypertension, and may partially explain the principal clinical manifestations of hypertensive retinopathy itself. Furthermore, these data imply that anti-VEGF therapies may prove therapeutically effective for hypertensive retinopathy and/or ameliorating the deleterious effects of coexistent hypertension on VEGF-associated disorders such as diabetic retinopathy.

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Section: Suzuma and Associatesmentioning

confidence: 96%

“…9A) or the AT1 receptor inhibitor candesartan cilexetil TCV-116 (Fig. 9B) (75,76,78). SHR rats had elevated baseline systolic, diastolic, and mean blood pressures (P < 0.001 for mean and systolic; 0.014 ≤ P ≤ 0.047 for diastolic) compared to WKY controls (Table 1).…”

Section: Suzuma and Associatesmentioning

confidence: 99%

Cyclic Stretch and Hypertension Induce Retinal Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor—2

et al. 2001

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“…The present paper compares directly the antihypertensive efficacy and tolerability of two AT 1 -receptor blockers, candesartan cilexetil 8 mg (13)(14)(15)(16), and losartan 50 mg (17)(18)(19)(20), in adult patients with mild-tomoderate essential hypertension, using clinic measurements and 36-h ambulatory BP monitoring (ABPM). The present paper compares directly the antihypertensive efficacy and tolerability of two AT 1 -receptor blockers, candesartan cilexetil 8 mg (13)(14)(15)(16), and losartan 50 mg (17)(18)(19)(20), in adult patients with mild-tomoderate essential hypertension, using clinic measurements and 36-h ambulatory BP monitoring (ABPM).…”

Section: Introductionmentioning

confidence: 99%

A placebo-controlled comparison of the efficacy and tolerability of candesartan cilexetil, 8 mg, and losartan, 50 mg, as monotherapy in patients with essential hypertension, using 36-h ambulatory blood pressure monitoring

Nisse-Durgeat

Mouret

et al. 2006

International Journal of Clinical Practice

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This double-blind, randomised, controlled study compared the efficacy of candesartan cilexetil 8 mg (n = 87) and losartan 50 mg (n = 89), once daily for 6 weeks, relative to placebo (n = 80) in patients with mild-to-moderate essential hypertension (diastolic blood pressure (DBP): 95-115 mmHg). Ambulatory BP measurements were done every 15 min over 36 h. At the end of the 6-week treatment, the mean change in DBP between the baseline and the 0-24-h period after the last dose of study medication was greater in patients receiving candesartan cilexetil 8 mg (-7.3 mmHg +/- 6.9 mmHg) compared with losartan 50 mg (-5.1 mmHg +/- 4.9 mmHg) (p < 0.05) or placebo (0.3 mmHg +/- 6.5 mmHg) (p < 0.001). The mean change in systolic BP (SBP) during this time was greater in patients receiving candesartan cilexetil 8 mg (-10.8 mmHg +/- 11.3 mmHg), or losartan 50 mg (-8.8 mmHg +/- 8.9 mmHg) than placebo (1.2 mmHg +/- 9.9 mmHg) (p < 0.001). Candesartan cilexetil 8 mg was associated with a greater reduction in DBP and SBP, relative to placebo, when compared with losartan 50 mg, during both daytime and night-time, and between 12 and 24 h after dosing (p < 0.001). Both active treatments were well tolerated. In patients with mild-to-moderate essential hypertension, candesartan cilexetil 8 mg therefore had greater, more consistent antihypertensive efficacy throughout the day and the night, and long-lasting efficacy after the last dose, compared with losartan 50 mg. This greater efficacy is maintained with an excellent tolerability associated with members of the angiotensin Il type 1-receptor blocker class.

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“…The latter is administered as a prodrug, candesartan cilexetil (Figure 4). This liberates candesartan, which binds strongly to the AT1 receptor [46, 47]. It is believed that an optimal clinical effect of these drugs, known collectively as “sartans,” requires high levels of target occupancy [48, 49].…”

Section: Angiotensin II At1 Receptor Antagonists and At2 Receptor mentioning

confidence: 99%

Discovery of Inhibitors of Insulin-Regulated Aminopeptidase as Cognitive Enhancers

Andersson

Hallberg

2012

International Journal of Hypertension

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The hexapeptide angiotensin IV (Ang IV) is a metabolite of angiotensin II (Ang II) and plays a central role in the brain. It was reported more than two decades ago that intracerebroventricular injection of Ang IV improved memory and learning in the rat. Several hypotheses have been put forward to explain the positive effects of Ang IV and related analogues on cognition. It has been proposed that the insulin-regulated aminopeptidase (IRAP) is the main target of Ang IV. This paper discusses progress in the discovery of inhibitors of IRAP as potential enhancers of cognitive functions. Very potent inhibitors of the protease have been synthesised, but pharmacokinetic issues (including problems associated with crossing the blood-brain barrier) remain to be solved. The paper also briefly presents an overview of the status in the discovery of inhibitors of ACE and renin, and of AT1R antagonists and AT2R agonists, in order to enable other discovery processes within the RAS system to be compared. The paper focuses on the relationship between binding affinities/inhibition capacity and the structures of the ligands that interact with the target proteins.

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Candesartan Cilexetil: An Angiotensin II Receptor Blocker

Cited by 13 publications

References 42 publications

Cyclic Stretch and Hypertension Induce Retinal Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor—2

Cyclic Stretch and Hypertension Induce Retinal Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor—2

A placebo-controlled comparison of the efficacy and tolerability of candesartan cilexetil, 8 mg, and losartan, 50 mg, as monotherapy in patients with essential hypertension, using 36-h ambulatory blood pressure monitoring

Discovery of Inhibitors of Insulin-Regulated Aminopeptidase as Cognitive Enhancers

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