DIFFERENTIAL EXPRESSION AND EFFECT OF 1,25-DIHYDROXYVITAMIN D-3 ON MYOSIN IN ARTERIAL TREE OF RATS

The hypothesis that 1,25-dihydroxyvitamin DQ [1,25(OH)(2)D-3, also known as calcitriol] modulates myosin expression in vascular smooth muscle was tested. Wistar-Kyoto or spontaneously hypertensive rats given intraperitoneal injections of 25 ng 1,25(OH)(2)D-3/100 g body weight for varying periods of time showed a greater than twofold increase in aortic mRNA encoding the myosin regulatory light chain relative to 18S rRNA (P < 0.05). 1,25(OH)(2)D-3 administration to Wistar rats caused a significant increase in the aortic content of total myosin regulatory light chain and total myosin heavy chain. The increase in myosin light chain was the result of a specific increase in expression of its smooth muscle isoform [control = 65.2 +/- 3.4% vs. 1,25(OH)(2)D-3 = 78.7 +/- 3.6%, P = 0.020]. 1,25(OH)(2)D-3 had no effect on total myosin light chain or heavy chain in the superior mesenteric artery. The hormone did, however, increase the proportion of the smooth muscle isoform of the light chain in this vessel [control = 81.4 +/- 2.6% vs. 1,25(OH)(2)D-3 = 88.8 +/- 2.1%, P = 0.048]. In branch II and III mesenteric resistance arteries, 1,25(OH)(2)D-3 significantly increased the active stress response to 10 mu mol/l norepinephrine but was without effect on total myosin light chain or heavy chain content or on the relative expression of the myosin light chain isoforms [control = 94.0 +/- 1.4% vs. 1,25(OH)(2)D-3 = 95.8 +/- 1.1%, P = 0.33]. We conclude that 1) 1,25(OH)(2)D-3 enhances expression of myosin light chain and heavy chain in the aorta but not the more muscular mesenteric arteries, 2) the increase in light chain is the result of an increase in the smooth muscle isoform of the protein, raising the possibility that 1,25(OH)(2)D-3 exerts a differentiating effect in the aorta, 3) there is differential distribution and 1,25(OH)(2)D-3 responsiveness of the smooth muscle isoform of the light chain along the arterial tree, and 4) 1,25(OH)(2)D-3 enhances stress generation in the resistance artery by an effect that is independent of its pro-myosin activity.