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Ca²⁺ signaling in mouse mesenteric small arteries: myogenic tone and adrenergic vasoconstriction

Department of Physiology, School of Medicine, University of Maryland, Baltimore, Maryland

Submitted 23 June 2006 ; accepted in final form 10 November 2006

Arteries that have developed myogenic tone (MT) are in a markedly different physiological state compared with those that have not, with higher cytosolic [Ca²⁺] and altered activity of several signal transduction pathways. In this study, we sought to determine whether ₁-adrenoceptor-induced Ca²⁺ signaling is different in pressurized arteries that have spontaneously developed MT (the presumptive physiological state) compared with those that have not (a common experimental state). At 32°C and intraluminal pressure of 70 mmHg, cytoplasmic [Ca²⁺] was steady in most smooth muscle cells (SMCs). In a minority of cells (34%), however, at least one propagating Ca²⁺ wave occurred. ₁-Adrenoceptor activation (phenylephrine, PE; 0.1–10.0 µM) caused strong vasoconstriction and markedly increased the frequency of Ca²⁺ waves (in virtually all cells). However, when cytosolic [Ca²⁺] was elevated experimentally in these arteries ([K⁺] 20 mM), PE failed to elicit Ca²⁺ waves, although it did elevate [Ca²⁺] (F/F₀) further and caused further vasoconstriction. During development of MT, the cytosolic [Ca²⁺] (F/F₀) in individual SMCs increased, Ca²⁺ waves disappeared (from SMCs that had them), and small Ca²⁺ ripples (frequency 0.05 Hz) appeared in 13% of cells. PE elicited only spatially uniform increases in [Ca²⁺] and a smaller change in diameter (than in the absence of MT). Nevertheless, when cytosolic [Ca²⁺] and MT were decreased by nifedipine (1 µM), PE did elicit Ca²⁺ waves. Thus ₁-adrenoceptor-mediated Ca²⁺ signaling is markedly different in arteries with and without MT, perhaps due to the elevated [Ca²⁺], and may have a different molecular basis. ₁-Adrenoceptor-induced vasoconstriction may be supported either by Ca²⁺ waves or by steady elevation of cytoplasmic [Ca²⁺], depending on the amount of MT.

phenylephrine; confocal microscopy; calcium waves; smooth muscle; imaging

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