MAP3K11 and hypertensive disorder: We demonstrate that (a) MLK3 functioned as a PKG1α-interacting partner and kinase substrate; (b) MLK3 was required for therapeutic effects of sildenafil on LV function after 7-day pressure overload; (c) MLK3 deletion led to hypertension and increased vascular stiffness in mice; (d) MLK3 was not required for the pressure lowering effects of PKG1α stimulation; and (e) pharmacological inhibition of MLK3 kinase activity induced LV dysfunction but did not increase BP.