Pulmonary hypertension associated with diazoxide: the SUR1 paradox

Figures

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  FIGURE 1. Potential beneficial effects of sulfonylurea receptor (SUR)1 and SUR2 activation in the pathophysiology of pulmonary hypertension (PH). a) SUR1 is expressed by human pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs). In the pulmonary arterial hypertension (PAH) and experimental PH context, SUR1 expression is unchanged compared to the control condition. Pharmacological activation of SUR1 by two different compounds (diazoxide and NN414) mediated pulmonary arterial relaxation, reduced pulmonary vessel neomuscularisation and reduced the development of experimental PH. b) Both human PAECs and PASMCs express SUR2A and SUR2B. In the PAH and experimental PH context, SUR2A and SUR2B are still expressed compared to the control condition. Pharmacological activation of SUR2A or SUR2B by pinacidil compound mediated pulmonary arterial relaxation, reduced pulmonary vascular remodelling and reduced the development of experimental PH.

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  FIGURE 2. Results of the disproportionality analyses for pulmonary hypertension (standardised medical query, narrow) and pulmonary arterial hypertension (preferred term) for diazoxide alone, sulfonylurea receptor (SUR)1 activators (narrow: only pinacidil, cromakalim and diazoxide) and SUR1 inhibitors. Number of reported cases (n event), total number of cases reported for drugs or groups of drugs of interest (n drug) and information component (IC) values (95% credibility intervals (CrI)) are presented. Bold type represents statistical significance.