The contribution of VEGF signalling to fostamatinib-induced blood pressure elevation.

ABSTRACT:

Background and purpose

Fostamatinib is an inhibitor of spleen tyrosine kinase (TK). In patients, fostamatinib treatment was associated with increased BP. Some TK inhibitors cause BP elevation, by inhibiting the VEGF receptor 2 (VEGFR2). Here, we have assessed the mechanistic link between fostamatinib-induced BP elevation and inhibition of VEGF signalling.

Experimental approach

We used conscious rats with automated blood sampling and radio telemetry and anaesthetized rats to measure cardiovascular changes. Rat isolated aorta and isolated hearts, and human resistance vessels in vitro were also used. NO production by human microvascular endothelial cells was measured with the NO-dependent probe, DAF-FM and VEGFR2 phosphorylation was determined in mouse lung, ex vivo.

Key res

SUBMITTER: Skinner M 

PROVIDER: S-EPMC3997272 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature