Iatrogenic hypertension: a bioinformatic analysis

It is well known that a myriad of medications and substances can induce side effects that are related to blood pressure (BP) regulation. This study aims to investigate why certain drugs tend to cause iatrogenic hypertension (HTN) and focus on drug targets that are implicated in these conditions. Databases and resources such as SIDER, DrugBank, and Genomatix were utilized in order to bioinformatically investigate HTN-associated drug target-genes for which HTN is a side effect. A tree-like map was created, representing interactions between 198 human genes that relate to the blood pressure system. 72 HTN indicated drugs and 160 HTN-inducing drugs were investigated. HTN-associated genes affected by these drugs were identified. HTN indicated drugs, which target nearly all branches of the interaction tree, were shown to exert an effect on most functional sub-systems of the BP regulatory system; and specifically, for the adrenergic and dopaminergic receptor pathways. High prevalence (25 genes) of shared targets between the HTN indicated and HTN-inducing drug categories was demonstrated. We focus on six drug families which are not indicated for HTN treatment, yet are reported as a major cause for blood pressure side effects. We show the molecular mechanisms that may lead to this iatrogenic effect. Such an analysis may have clinical implications that could allow for the development of tailored medicine with fewer side effects.