Calcium signaling in mouse mesenteric small arteries: myogenic tone and adrenergic vasoconstriction

In this study, we sought, first, to observe (through confocal imaging of fluo‐4 fluorescence) the changes in [Ca 2+ ] in individual smooth muscle cells (SMC) of mouse mesenteric small arteries during development of MT, and second, to determine whether α 1 ‐adrenoceptor induced Ca 2+ signaling is influenced by MT. Before MT developed spontaneously, at 32°C and intraluminal pressure of 70 mm Hg, propagating Ca 2+ waves (previously shown to be dependent on InsP 3 receptors) were present in most SMC. In these arteries, α 1 ‐adrenoceptor activation (phenylephrine, PE, 0.1 to 10.0 μM) caused strong vasoconstriction and markedly increased the frequency of Ca 2+ waves. However, when cytosolic [Ca 2+ ] was elevated experimentally ([K + ] o , 20 mM), PE caused vasoconstriction and raised [Ca 2+ ], but failed to elicit Ca 2+ waves. During the spontaneous development of MT, the cytosolic [Ca 2+ ] in individual SMC increased to an estimated level of ~ 400 nM. Ca 2+ waves disappeared, and small Ca 2+ ‘ripples’ appeared in ~ 25% of cells (frequency; ~ 0.05 Hz). The angiotensin II competitive antagonist, [Sar 1 , Ile 8 ]‐Ang II (10 nM), inhibited the ripples and caused a small (< 10 %) decrease in MT. In arteries with MT, PE elicited only spatially uniform increases in [Ca 2+ ], and smaller vasoconstriction (than in absence of MT). However, when cytosolic [Ca 2+ ] was decreased by nifedipine, PE did again elicit Ca 2+ waves. RT‐PCR indicated the presence of Type 1 InsP 3 receptor (Ca 2+ inactivated) in these arteries. We propose that in mouse arteries with MT, the markedly elevated cytosolic [Ca 2+ ] and/or local Ca 2+ influx around L‐type Ca 2+ channels may inactivate Type 1 InsP3 receptors, accounting for inability of α 1 ‐adrenoceptor agonists to elicit Ca 2+ waves.