Secondhand Smoke Exposure Impairs Ion Channel Function and Contractility of Mesenteric Arteries

Abstract

Cigarette smoke, including secondhand smoke (SHS), has significant detrimental vascular effects, but its effects on myogenic tone of small resistance arteries and the underlying mechanisms are understudied. Although it is apparent that SHS contributes to endothelial dysfunction, much less is known about how this toxicant alters arterial myocyte contraction, leading to alterations in myogenic tone. The study's goal is to determine the effects of SHS on mesenteric arterial myocyte contractility and excitability. C57BL/6J male mice were randomly assigned to either filtered air (FA) or SHS (6 hours/day, 5 days/week) exposed groups for a 4, 8, or 12-weeks period. Third and fourth-order mesenteric arteries and arterial myocytes were acutely isolated and evaluated with pressure myography and patch clamp electrophysiology, respectively. Myogenic tone was found to be elevated in mesenteric arteries from mice exposed to SHS for 12 weeks but not for 4 or 8 weeks. These results were correlated with an increase in L-type Ca2+ channel activity in mesenteric arterial myocytes after 12 weeks of SHS exposure. Moreover, 12 weeks SHS exposed arterial myocytes have reduced total potassium channel current density, which correlates with a depolarized membrane potential (Vm). These results suggest that SHS exposure induces alterations in key ionic conductances that modulate arterial myocyte contractility and myogenic tone. Thus, chronic exposure to an environmentally relevant concentration of SHS impairs mesenteric arterial myocyte electrophysiology and myogenic tone, which may contribute to increased blood pressure and risks of developing vascular complications due to passive exposure to cigarette smoke.

Spatiotemporal Control of Vascular Ca V 1.2 by α1 C S1928 Phosphorylation

“…We used a modified PLA validated by us and others to examine α1 C oligomerization/clustering. 46 , 47 A similar modified PLA has been used to examine oligomerization/clustering of epidermal growth factor receptors and α-synuclein. 48 , 49 In our modified PLA, a single α1 C monoclonal antibody is labeled with the PLUS or MINUS probe.…”

“…The modified PLA assay ( Figure S4A and 46 , 47 ) showed that PLA puncta density was significantly elevated in WT but not S1928A, STZ arterial myocytes compared with WT/S1928A sham cells (Figure 6 A, Table S11 ). No PLA signal was observed when the primary antibody was omitted ( Figure S5A ).…”

“…References 3 , 5 , 7 , 17 , 18 , 23 , 26 – 28 , 30 , 31 , 33 , 35 , 36 , 40 , 41 , 46 – 49 , 52 , 55 …”

Diabetes and Excess Aldosterone Promote Heart Failure With Preserved Ejection Fraction

“…Freshly isolated mesenteric artery segments were mounted in a 5‐mL myograph chamber to determine arterial diameter changes in response to changes in intraluminal pressure as previously described. 27 …”

Enhanced Vascular Contractility Following Secondhand Smoke Exposure: A Pathological “Double-hit” to Critical Smooth Muscle Ion Channels

“…In this issue's article, “Secondhand Smoke Exposure Impairs Ion Channel Function and Contractility of Mesenteric Arteries,” 3 Le et al . provide elegant inroads into this question.…”