During vascular remodeling in adult organisms, new capillary growth is often coupled with the adaptation of arterioles and venules, a process that requires the recruitment and differentiation of precursor cells into smooth muscle. We studied the in vivo adaptation of microvessels in the presence of elevated pressure and circumferential wall stress using a ligation strategy for mesenteric microvascular networks. Acute pressure increases of 42.6+/-18% and 17.1+/-2.3% were respectively elicited in the 25- to 30-microm-diameter venules and arterioles supplying the networks. Wall shear rates were not significantly changed; however, diameters were increased in >10-microm-diameter venules and >20-microm-diameter arterioles. Smooth muscle cell contractile phenotype was determined in all microvessels by observing the expression of smooth muscle myosin heavy chain (SM-MHC; a marker of fully differentiated smooth muscle) and smooth muscle alpha-actin (a marker for all smooth muscle, including immature smooth muscle of fibroblast/pericyte lineage). The ratio of SM-MHC positive vessel length to smooth muscle alpha-actin-positive vessel length increased >2-fold after 5 and 10 days of the ligation treatment. Smooth muscle proliferation was studied by bromodeoxyuridine incorporation, and the increase in SM-MHC-labeled microvessel length density was accompanied by no measurable change in proliferation of SM-MHC-labeled cells 5 and 10 days after ligation. These results indicate that after a period of 5 or 10 days, mesenteric microvessels <40 microm in diameter exposed to elevated pressure and wall strain exhibit an enhanced coverage of mature, fully differentiated smooth muscle cells.