1. Absence of PKD1 and mechanosensitivity

2. Dissect 3 rd order arteries Incubate in papain/DTT @ 37 ° C Incubate in Collagenase F/H @ 37 ° C Triturate Let rest 1 hour @ 4°C Start recording Use cells within 5 hours post 4 ° C Smooth muscle  -actin Hoechst nuclear stain Acute dissociation of mesenteric smooth muscle cells

3. 1.5 pA Cre N = 20

4. 1.5 pA Cre Lox/Lox/Cre N = 20 N = 48

5. Cell attached

7. Myogenic response: ability of vascular smooth muscle to constrict in response to an increase in transmural pressure, or dilate in response to reduced transmural pressure. Myogenic response is essential for setting of vascular resistance. The mechanism of pressure sensing remains to be determined.

8. Techniques expérimentales Artériographie isobarique 150 µm Artères mésentériques Souris transgéniques

9. Increase in intraluminal pressure VSM membrane stretch VSM membrane depolarization Opening of voltage-gated Ca 2+ channels Ca 2+ influx Phosphorylation of MLCK Activation of Ca 2+ /CaMK Phosphorylation of MLC Contraction Steps in the myogenic response Is myogenic tone altered in pkd1 del mice?

10. Tonus myogénique

16. Increase in intraluminal pressure VSM membrane stretch VSM membrane depolarization Opening of voltage-gated Ca 2+ channels Ca 2+ influx Phosphorylation of MLCK Activation of Ca 2+ /CaMK Phosphorylation of MLC Contraction Steps in the myogenic response Is myogenic tone altered in pkd1 del mice?

25. I. D. O. D.

30. Conclusion Mechanosensitivity of smooth muscle cells of resistance arteries is sign. reduced in PKD1 del mice. Myogenic tone is significantly reduced in PKD1 del mice. The threshold for the myogenic tone is shifted to higher pressure values in PKD1 del mice. Responses to PHE and K are unaltered in PKD1 del mice. Passive properties are unaltered between the different genotypes.