HIV transgene expression impairs K+ channel function in the pulmonary vasculature

Human immunodeficiency virus (HIV) infection is an established risk factor for pulmonary arterial hypertension (PAH), however the pathogenesis of HIV-related PAH remains unclear. Since K+ channel dysfunction is a common marker in most forms of PAH, our aim was to analyse if the expression of HIV proteins is associated with impairment of K+ channel function in the pulmonary vascular bed. HIV transgenic mice (Tg26) expressing seven of the nine HIV viral proteins and wild type (Wt) mice were used. Hemodynamic assessment was performed by echocardiography and catheterization. Vascular reactivity was studied in endothelium-intact pulmonary arteries (PA). K+ currents were recorded in freshly isolated PA smooth muscle cells (PASMC) using the patch-clamp technique. Gene expression was assessed using RT-PCR. PASMC from Tg26 mice had reduced K+ currents and were more depolarized that those from Wt. While Kv1.5 currents were preserved, pH-sensitive non-inactivating background currents (IKN) were nearly abolished in P...