Rapid ASM contraction and relaxation is essential for dynamic sympathetic control of peripheral resistance. Whereas contraction of ASM is triggered by an increase in free cytosolic Ca²⁺ ([Ca²⁺]_i), the resultant forces may vary depending on Ca²⁺-sensitization of the contractile machinery. This study tested the hypothesis that balance of Ca²⁺-dependent and Ca²⁺-independent mechanisms of contraction is controlled by sympathetic innervation and changes during its development. We demonstrate that establishment of sympathetic control of rat saphenous artery over the first month of postnatal development is accompanied by Ca²⁺-desensitization of ASM contraction, which is reversed by surgical denervation of the artery. The ASM from the adult rats, but not from their denervated mates, required higher [Ca²⁺ ]_i to generate isometric forces comparable to those produced by ASM of the 1–2-week-old rats in response to the a- adrenergic or thromboxane receptor activation. The progress of sympathetic innervation was associated with an increased expression of myosin light chain kinase, myosin light chain phosphatase targeting subunit and h-caldesmon, i.e. the proteins that mediate Ca²⁺-dependent regulation. In contrast, expression of Rho-kinase, ERK and p38 MAP-kinases, that are involved in Ca²⁺-sensitization, was gradually diminished. The opposite changes in the expression profiles of these proteins, associated with increased Ca²⁺ -sensitivity of contraction, were observed upon denervation of ASM in the adult rats. Altogether, these data suggest that sympathetic nerves exert trophic function in establishment of rapid contractile phenotype of ASM. Supported by RFBR (grant 07-04-01527) and cooperation program Uni-Rostock - MSU.