Impaired vascular contractility and blood pressure homeostasis in the smooth muscle alpha-actin null mouse

The smooth muscle (SM) alpha -actin gene activated during the early stages of embryonic cardiovascular development is switched off in late stage heart tissue and replaced by cardiac and skeletal alpha -actins. SM alpha -actin also appears during vascular development, but becomes the single most abun dant protein in adult vascular smooth muscle cells. Tissue-specific express ion of SM alpha -actin is thought to be required for the principal force-ge nerating capacity of the vascular smooth muscle cell. We wanted to determin e whether SM alpha -actin gene expression actually relates to an actin isof orm's function. Analysis of SM alpha -actin null mice indicated that SM alp ha -actin is not required for the formation of the cardiovascular system. A lso, SM alpha -actin null mice appeared to have no difficulty feeding or re producing. Survival in the absence of SM alpha -actin may result from other actin isoforms partially substituting for this isoform. In fact, skeletal alpha -actin gene, an actin isoform not usually expressed in vascular smoot h muscle, was activated in the aortas of these SM alpha -actin null mice. H owever, even with a modest increase in skeletal alpha -actin activity, high ly compromised vascular contractility, tone, and blood flow were detected i n SM alpha -actin-defective mice. This study supports the concept that SM a lpha -actin has a central role in regulating vascular contractility and blo od pressure homeostasis, but is not required for the formation of the cardi ovascular system.