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

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 alpha(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 degrees 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. alpha 1-Adrenoceptor activation ( phenylephrine, PE; 0.1 - 10.0 mu M) 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/ F-0) further and caused further vasoconstriction. During development of MT, the cytosolic [ Ca2+] ( F/ F-0) in individual SMCs increased, Ca2+ waves disappeared ( from SMCs that had them), and small Ca2+ ripples ( frequency similar to 0.05 Hz) appeared in similar to 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 mu M), PE did elicit Ca2+ waves. Thus alpha 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. alpha 1-Adrenoceptor- induced vasoconstriction may be supported either by Ca2+ waves or by steady elevation of cytoplasmic [ Ca2+], depending on the amount of MT.