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

The smooth muscle (SM) α-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 α-actins. SM α-actin also appears during vascular development, but becomes the single most abundant protein in adult vascular smooth muscle cells. Tissue-specific expression of SM α-actin is thought to be required for the principal force-generating capacity of the vascular smooth muscle cell. We wanted to determine whether SM α-actin gene expression actually relates to an actin isoform's function. Analysis of SM α-actin null mice indicated that SM α-actin is not required for the formation of the cardiovascular system. Also, SM α-actin null mice appeared to have no difficulty feeding or reproducing. Survival in the absence of SM α-actin may result from other actin isoforms partially substituting for this isoform. In fact, skeletal α-actin gene, an actin isoform not usually expressed in vascular smooth muscle, was activated in the aortas of these SM α-actin null mice. However, even with a modest increase in skeletal α-actin activity, highly compromised vascular contractility, tone, and blood flow were detected in SM α-actin-defective mice. This study supports the concept that SM α-actin has a central role in regulating vascular contractility and blood pressure homeostasis, but is not required for the formation of the cardiovascular system.