Inhibitor Reversibel

All humoral factors that are involved in blood pressure regulation, such as catecholamines and aldosterone, failed to show a relationship between their deregulation and hypertension during treatment with sorafenib.These results further support the idea that the effect of angiogenesis inhibitors on blood pressure is determined at the level of the vasculature itself.Blockade of VEGF signalling may also disturb the balance between VEGF and endothelin.Endothelin is a potent endogenous vasoconstrictor and its expression correlates with that of VEGF.The exact role of their interaction is unknown, but one might expect that they function to keep the blood pressure tightly in balance. Increased peripheral resistance of the vasculature, similar to blood volume overload, may be responsible for both hypertension and a reduced LVEF, and both may precede congestive heart failure.Therefore, these two toxicities are closely related.They studied the effect of angiogenic gene therapy and found that the transplantation of VEGF and insulinlike growth factor expressing bonemarrowderived cells was able to improve left ventricular cardiac function due to increased cardiac angiogenesis.This study, together with the clinical observations that angiogenesis inhibitors reduce the LVEF, underscore the need for measures of LVEF to be determined routinely in patients treated with angiogenesis inhibitors.Hypertension and a reduced LVEF during treatment may complicate the opportunity to use these agents in adjuvant or lifelong treatment strategies.Another side effect that could be related to hypertension is encephalopathy.Two case reports of bevacizumab and one case report of sorafenibassociated reversible posterior leukoencephalopathy syndrome have been published.The most frequent cause of RPLS is thought to be hypertension, and it might be related to endothelial dysfunction.VEGF expression is low in hypofunctional thyroid glands.For this reason, other factors such as PDGF or KIT may have a role in thyroid homeostasis, but so far no data have been published on the role of these factors in thyroid function.VEGF also has an important role in endocrine glands other than the thyroid.For example, in pancreatic islets VEGF has a role in the formation of fenestrations of the islet capillaries.Interestingly, in mice treated with a VEGFR inhibitor, a significant reduction of vessel density was observed in several organs, including the thyroid gland, adrenal cortex, pituitary, choroid plexus and small intestinal villi.However, we are unaware of any clinical data on the effects of VEGF on these other glands.Renal function is partly regulated by VEGF, and the inhibition of VEGF causes mild proteinuria. As proteins are normally reabsorbed from urine, proteinuria is due to a decreased reabsorption or increased filtration.Up to of patients treated with bevacizumab Citric acid developed proteinuria, but this proteinuria was mostly asymptomatic.The importance of VEGF for the kidney is reflected by its expression in the normal renal cortex as well as in kidney tumours, and VEGF is highly expressed in the glomeruli and tubules, and is involved in kidney repair.However, the underlying mechanism of increased proteinuria owing to treatment with angiogenesis inhibitors is unknown.A preclinical study in rats Rebeprazole sodium showed that VEGF has a role in the function of podocytes and renal endothelial cells to prevent proteinuria.Alternatively, or in parallel, the endothelial cell lining might be disturbed in patients treated with angiogenesis inhibitors, causing the extravasation of plasma proteins into the extracellular matrix or urine.

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