K _V 1.3 channels are novel determinants of macrophage‐dependent endothelial dysfunction in angiotensin II‐induced hypertension in mice

Background and Purpose K V 1.3 channels are expressed in vascular smooth muscle cells (VSMCs), where they contribute to proliferation rather than contraction participate remodelling. also macrophages, assemble with 1.5 (K 1.3/K 1.5), whose activation generates a current. In the ratio is increased by classical (M1). Whether these involved angiotensin II (AngII)‐induced remodelling, whether can modulate macrophage phenotype hypertension, remains unknown. We characterized role of damage hypertension. Experimental Approach used AngII‐infused mice treated two selective channel inhibitors (HsTX[R14A] [EWSS]ShK). Vascular function structure were measured using wire pressure myography, respectively. VSMC electrophysiology studied patch‐clamp technique; gene expression was analysed RT‐PCR. Key Results AngII aorta peritoneal macrophages which abolished HsTX[R14A] treatment. inhibition did not prevent or stiffness but corrected AngII‐induced infiltration endothelial dysfunction small mesenteric arteries and/or aorta, via mechanism independent electrophysiological changes VSMCs. modified properties indicating an M1‐like activated state, enhanced proinflammatory cytokines that induced dysfunction. These effects prevented blockade. Conclusions Implications unravelled new for macrophage‐dependent might be due modulation phenotype.