Impaired ﬂow-induced dilation in mesenteric resistance arteries from receptor protein tyrosine phosphatase- (cid:1) -deﬁcient mice

Impaired ﬂow-induced dilation in mesenteric resistance arteries from receptor protein tyrosine phosphatase- (cid:1) -deﬁcient mice. Am Physiol Heart Circ Physiol 00512.2004. —The transmembrane receptor-like protein tyrosine phosphatase- (cid:1) (RPTP (cid:1) ) is thought to play an important role in cell-cell adhesion-mediated processes. We recently showed that RPTP (cid:1) is predominantly expressed in the endothelium of arteries and not in veins. Its involvement in the regulation of endothelial adherens junctions and its speciﬁc arterial expression suggest that RPTP (cid:1) plays a role in controlling arterial endothelial cell function and vascular tone. To test this hypothesis, we analyzed myogenic responsiveness, ﬂow-induced dilation, and functional integrity of mesenteric resistance arteries from RPTP (cid:1) -deﬁcient (RPTP (cid:1) (cid:2) / (cid:2) ) mice and from wild-type littermates. Here, we show that cannulated mesenteric arteries from RPTP (cid:1) (cid:2) / (cid:2) mice display signiﬁcantly decreased ﬂow-induced dilation. In contrast, mechanical properties, myogenic responsiveness, responsiveness to the vasoconstrictors phenylephrine or U-46619, and responsiveness to the endothelium-dependent vasodilators methacholine or bradykinin were similar in both groups. Our results imply that RPTP (cid:1) is involved in the mechanotransduction or accessory signaling path-ways that control shear stress responses in mesenteric resistance arteries. temperature monitoring, a temperature-controlled heating pad, and an infrared lamp. Wire myograph experiments. The vasoconstrictor and relaxant effects of phenylephrine, U-46619, methacholine, and bradykinin on small resistance mesenteric arteries of knockout and wild-type mice were investigated using an isometric wire myograph. Both male and female mice were anesthetized with a mixture of ketamine (125 mg/kg ip) and xylazine (7.5 mg/kg ip). The mesenteric vascular bed was isolated, dissected free from its connective tissue, and transferred to physiological Tyrode solution [composition (in mmol/l) of 118.5 NaCl, 4.7 KCl, 1.2 MgCl 2 , 2.5 CaCl 2 , 1.2 KH 2 PO 4 , 25 NaHCO 3 , 5.5 glucose, and 0.024 EDTA; oxygenated with 95% O 2 -5% CO 2 ] at room temperature. Small segments of the ﬁrst-branch mesenteric artery were prepared and mounted in an isometric wire myograph (Danish Myo Technology; Aarhus, Denmark). The preparations were equilibrated for 15 min, and, subsequently, the diameter was determined by a normalization procedure, according to Mulvany and Halpern (24). In this procedure, passive tension of the relaxed vessel is measured as a function of internal circumference, as set by the distance between the two wires. From these data and using the Laplace relationship, the equivalent diameter at a distending pressure of 100 mmHg is determined. The passive tension was set to 5 mN/mm (4). After an additional 15-min equilibration period, the preparations were exposed three times to a depolarizing Tyrode solution (equimo-lar substitution of 120 mmol/l KCl for NaCl) for 5 min with a 20-min interval. Hereafter, cumulative concentration response curves were constructed for the (cid:9) 1 -adrenoceptor agonist L -phenylephrine and the thromboxane A (cid:9)