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Notch3 receptor (Notch3R) highly implicated in the mechanisms of vascular differentiation plays a key role in the control of arterial integrity. Notch3R KO vascular smooth muscle cells exhibited marked alterations in shape and size. The goal of this study was to analyse the physiological consequences of these morphological alterations. Mesenteric and tail caudal arteries were isolated from 5 KO and 6 WT mice, 12 weeks old, to be analysed on pressure and wire myographs. Passive diameter (PD) from tail artery was similar in both strains (WT: 243 ± 12 vs KO: 217 ± 12 µm). Nevertheless myogenic tone was significantly reduced (77 %) in KO (WT: 32.2 ± 3.7 vs. KO: 10.7 ± 2.1 % of PD 75 mmHg. P<0.05). This was associated to a significant improvement of the flow-mediated dilation. (86 % for a 50 µL/min flow, WT 44.6 ± 5.0 vs. 86.7 ± 5.2 % dilation, P<0.001). Tail artery from KO mice exhibited also an increased phenylephrine-induced constriction but no change in ACh-induced dilation. In mesenteric artery, vascular mechano-transduction was not affected by the depletion in Notch3R. However in this latter artery ACh-induced dilation was reduced. This study clearly showed the predominant role played by Notch3R in the control of vascular mechano-transduction with opposite effects on myogenic tone and flow mediated dilation. Notch3R might thus have a key role in the control of vascular mechano-transduction of muscular arteries. The pathophysiologic consequences of this observation have to be determined. [ABSTRACT FROM AUTHOR]