Does a reduction of vascular relaxation promote hypertension?

Background Alterations in vascular relaxation have been reported in various models of hypertension. With its tonic activity, the NO/cGMP signalling cascade plays an important role in the regulation of the vascular tone. In blood vessels, NO is continuously being produced by the endothelial NO synthases (eNOS) which leads to cGMP production by stimulating the NO-sensitive guanylyl cyclases (NO-GCs). In vascular smooth muscle cells, two NO-GC isoforms, NO-GC1 and NO-GC2, mediate relaxation, with NO-GC1 being responsible for approximately 90% of the NO-stimulated cGMP formation. Deletion of eNOS or both NO-GCs abrogates endothelium-dependent relaxation and causes substantial hypertension. However, deletion of only NO-GC1 does not lead to hypertension despite a 50% reduction of endothelium-dependent relaxation.