Modulation of resistance artery force generation by extracellular
ca2+.
Bian, Ka, and Richard D. Bukoski.
Hypertension and Vascular Research, Departments of Internal
Medicine and Physiology & Biophysics, University of Texas Medical
Branch, Galveston Island, Texas 77555
APStracts 2:0050H, 1995.
We tested the hypothesis that increasing extracellular Ca2+ (Cao) over
a physiologic concentration range depresses vascular smooth muscle
force generation by altering the intracellular Ca2+ (Cai)-force
relationship. Mesenteric resistance arteries were isolated from
Wistar rats; Cai and isometric force were measured using a fura-based
method and wire myography. Vessels were depleted of releasable Cai by
repeated contraction with norepinephrine; Cao was then cumulatively
added back from 0.025-2.5 mmol/L in the presence of an agonist. With
norepinephrine, serotonin, PGF2[alpha], and K+, Cao from 0.025 to 0.8
mmol/L induced a graded increase in Cai and active stress. With the
receptor agonists, but not K+, raising Cao from 0.8 to 1.6 and 1.6 to
2.5 mmol/L decreased active stress to 82+6 and 54+6% of maximum,
p<0.05. Although there was a transient decrease in Cai in response to
both 1.6 and 2.5 mmol/L Cao, steady state Cai only decreased
significantly in response to 2.5 mmol/L Cao (85+3% of maximum).
Inhibition of the sarcoplasmic reticular Ca2+-ATPase with 1 [mu]mol/L
thapsigargin had no effect on the decrease in force induced by high
Ca2+. The decrease in active stress induced by 1.6 and 2.5 mmol/L Cao
was inhibited by Ca2+ channel antagonists and by blockade of Ca2+
-activated K+ channels with charybdotoxin (with 1.6 mmol/L Cao,
control tension = 67+10% of maximum vs charybdotoxin = 99.2+1%,
p<0.05; n=9). Inhibition of protein kinase C with bisindolylmaleimide
or H7 depressed the contractile response to increasing Cao but had
little effect on the decrease in force induced by 1.6 and 2.5 mmol/L
Cao. We conclude that Ca0 limits force generation by depressing
myofilament Ca2+ sensitivity and decreasing Cai secondary to
activation of a Ca2+-sensitive K+ channel.
Received 2 June 1994; accepted in final form 30 January 1995.
APS Manuscript Number H480-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.