CALCIUM-ENTRY AND MYOGENIC PHENOMENA IN SKELETAL-MUSCLE ARTERIOLES

Studies were conducted to examine Ca2+ entry in several vasomotor situ ations related to myogenic properties of arterioles (basal tone, vasom otion, and responsiveness to alterations in intravascular pressure). I n vivo studies were performed on small cremaster muscle arterioles of anesthetized rats. Intravascular pressure was increased using the pres sure-box technique. Voltage-operated Ca2+ channel (VOC) activity was i nhibited by nifedipine or methoxyverapamil and was stimulated with BAY K 8644. To examine the effect of hyperpolarization, studies were perf ormed in the presence of pinacidil. Nifedipine and methoxyverapamil ex hibited a trend toward dose-dependent dilation; however, neither agent caused dilation comparable to adenosine (10(-4) M). BAY K 8644 produc ed a biphasic effect, constriction below 10(-8) M, and dilation at hig her levels. These data indicate that basal tone can be modulated by ag ents acting on VOCs; however, as high concentrations of nifedipine do not abolish tone, other mechanisms contribute. At similar concentratio ns, the Ca2+ channel antagonist significantly inhibited vasomotion, ab olishing vasomotion at concentrations above 5 x 10(-6) M. In contrast, BAY K 8644 caused a dose-dependent increase in vasomotion amplitude ( e.g., 269 +/- 52% of basal at 10(-7) M). Thus vasomotion appears highl y dependent on VOCs. Experiments per formed in the presence of the ant agonists/agonists indicated that VOCs are not the prime determinant of constrictor responses to acute increases in intravascular pressure. E xposure to pinacidil resulted in dose-dependent vasodilatation and inh ibition of vasomotion while showing little effect on acute myogenic re sponses. Similar effects of pinacidil were observed in isolated, cannu lated, cremaster arterioles. Collectively, these data suggest that dif ferent Ca2+ entry mechanisms underlie arteriolar basal tone, spontaneo us vasomotion, and responsiveness to acute increases in intravascular pressure.