Calcium entry and myogenic phenomena in skeletal muscle arterioles.
Studies were conducted to examine Ca2+ entry in several vasomotor situations related to myogenic properties of arterioles (basal tone, vasomotion, and responsiveness to alterations in intravascular pressure). In vivo studies were performed on small cremaster muscle arterioles of anesthetized rats. Intravascular pressure was increased using the pressure-box technique. Voltage-operated Ca2+ channel (VOC) activity was inhibited by nifedipine or methoxyverapamil and was stimulated with BAY K 8644. To examine the effect of hyperpolarization, studies were performed in the presence of pinacidil. Nifedipine and methoxyverapamil exhibited a trend toward dose-dependent dilation; however, neither agent caused dilation comparable to adenosine (10(-4) M). BAY K 8644 produced a biphasic effect, constriction below 10(-8) M, and dilation at higher levels. These data indicate that basal tone can be modulated by agents acting on VOCs; however, as high concentrations of nifedipine do not abolish tone, other mechanisms contribute. At similar concentrations, the Ca2+ channel antagonist significantly inhibited vasomotion, abolishing 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 highly dependent on VOCs. Experiments performed in the presence of the antagonists/agonists indicated that VOCs are not the prime determinant of constrictor responses to acute increases in intravascular pressure. Exposure to pinacidil resulted in dose-dependent vasodilatation and inhibition of vasomotion while showing little effect on acute myogenic responses. Similar effects of pinacidil were observed in isolated, cannulated, cremaster arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)
Hill
M A
MA
Department of Medical Physiology, College of Medicine, Texas A&M University, College Station 77843.
Meininger
G A
GA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000098:blood supply*; D020110:Pinacidil; D051381:Rats; D017207:Rats, Sprague-Dawley; D014666:Vasomotor System / Q000502:physiology
D002121:Calcium Channel Blockers; D006146:Guanidines; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020110:Pinacidil; D002118:Calcium