To clarify the role of Na(+)-H+ antiporter as a subcellular signal in cardiovascular system, we determined mRNA levels of the Na(+)-H+ antiporter in the vascular smooth muscles and pressure-overloaded hearts in rabbits. The expression of the Na(+)-H+ antiporter gene in rabbit aortas and hearts was much more prominent at embryonic and neonatal stages than in adults. The growth of C5, which is deficient in the Na(+)-H+ antiporter, was accelerated again when the activity was restored by transfecting cells with full-length cDNA for Na(+)-H+ antiporter in an expression vector. In pressure-overloaded hearts, the Na(+)-H+ antiporter mRNA was increased 2.5 fold of sham-operated rabbits at 3 days after aortic constriction, lasting for more than 2 weeks. We conclude from these results that activation of the Na(+)-H+ antiporter gene plays a key role in both cardiac hypertrophy and vascular smooth muscle cell proliferation.