TY - ABST

T1 - Significance of CaV3.2 T-type Ca2+ channels for pressure- and flow-dependent vasomotor responses in rat and mouse mesenteric small arteries

T2 - 11th International Symposium on Resistance Arteries

AU - Jensen, Lars Jørn

AU - Björling, K.

AU - Hansen, Pernille B. Lærkegaard

AU - Olsen, Miriam F.

PY - 2014/12

Y1 - 2014/12

N2 - We investigated the potential significance of CaV3.2 channels in the myogenic response (MR) and flow-mediated vasodilatation (FMVD). CaV3.2 channels were immunolocalized to EC and VSMC in rat and mouse small mesenteric arteries. The myogenic tone at pressures of 40-120 mmHg was significantly larger in young CaV3.2-/- mice (8-15 weeks) vs. age-matched WT mice (P<0.05; N=3-4), whereas no difference was observed in older (6-8 months) WT vs. KO mice (N=4-5). In young WT mice, the CaV3.2 blocker NiCl2 (30 µM) significantly enhanced myogenic tone (P<0.05; N=4), whereas in old WT mice this effect was not seen (N=4). In young and old CaV3.2-/- mice no effects of NiCl2 were observed. The FMVD response in rat mesenteric arteries was not blocked by L-NAME, but was almost abolished by the SKCa/IKCa channel blockers apamin/TRAM-34 (50 nM/1 µM) (P<0.01; N=6). Interestingly the vessels constricted to flow in the presence of 100 µM NiCl2 (P<0.001; N=6), and this led us to investigate FMVD in CaV3.2-/- mice. The FMVD response was not significantly different in old WT (N=8) vs. CaV3.2-/- mice (N=8), whereas preliminary data suggested a reduced FMVD in young KO mice. Expression of Cagna1A/C/G and TRPC1/3/6 mRNA was similar in WT vs. CaV3.2-/- mice. CONCLUSION: FMVD responses appear to rely on an endothelium-dependent hyperpolarization in rat small mesenteric arteries. CaV3.2 channels are negative feedback modulators of myogenic tone in small mesenteric artery in young mice. The age-dependent decline in CaV3.2-mediated negative feedback modulation in old animals might be clinically relevant.

AB - We investigated the potential significance of CaV3.2 channels in the myogenic response (MR) and flow-mediated vasodilatation (FMVD). CaV3.2 channels were immunolocalized to EC and VSMC in rat and mouse small mesenteric arteries. The myogenic tone at pressures of 40-120 mmHg was significantly larger in young CaV3.2-/- mice (8-15 weeks) vs. age-matched WT mice (P<0.05; N=3-4), whereas no difference was observed in older (6-8 months) WT vs. KO mice (N=4-5). In young WT mice, the CaV3.2 blocker NiCl2 (30 µM) significantly enhanced myogenic tone (P<0.05; N=4), whereas in old WT mice this effect was not seen (N=4). In young and old CaV3.2-/- mice no effects of NiCl2 were observed. The FMVD response in rat mesenteric arteries was not blocked by L-NAME, but was almost abolished by the SKCa/IKCa channel blockers apamin/TRAM-34 (50 nM/1 µM) (P<0.01; N=6). Interestingly the vessels constricted to flow in the presence of 100 µM NiCl2 (P<0.001; N=6), and this led us to investigate FMVD in CaV3.2-/- mice. The FMVD response was not significantly different in old WT (N=8) vs. CaV3.2-/- mice (N=8), whereas preliminary data suggested a reduced FMVD in young KO mice. Expression of Cagna1A/C/G and TRPC1/3/6 mRNA was similar in WT vs. CaV3.2-/- mice. CONCLUSION: FMVD responses appear to rely on an endothelium-dependent hyperpolarization in rat small mesenteric arteries. CaV3.2 channels are negative feedback modulators of myogenic tone in small mesenteric artery in young mice. The age-dependent decline in CaV3.2-mediated negative feedback modulation in old animals might be clinically relevant.

KW - Faculty of Health and Medical Sciences

KW - Calcium Channels, T-Type

KW - vascular smooth muscle cells

KW - Endothelial Cells

M3 - Conference abstract for conference

Y2 - 7 September 2014 through 11 September 2014

ER -