Modulation of resistance artery force generation by extracellular Ca2+.

We tested the hypothesis that increasing extracellular Ca2+ (Cao) over a physiological 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 mM in the presence of an agonist. With norepinephrine, serotonin, prostaglandin F2 alpha, and K+, Cao from 0.025 to 0.8 mM induced a graded increase in Cai and active stress. With the receptor agonists but not K+ raising Cao from 0.8 to 1.6 mM and from 1.6 to 2.5 mM decreased active stress to 82 +/- 6 and 54 +/- 6% of maximum, respectively, P < 0.05. Although there was a transient decrease in Cai in response to both 1.6 and 2.5 mM Cao, steady-state Cai only decreased significantly in response to 2.5 mM Cao (85 +/- 3% of maximum). Inhibition of the sarcoplasmic reticulum Ca(2+)-adenosinetriphosphatase with 1 microM 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 mM Cao was inhibited by Ca2+ channel antagonists and by blockade of Ca(2+)-activated K+ channels with charybdotoxin (with 1.6 mM Cao, control tension = 67 +/- 10% of maximum vs. charybdotoxin = 99.2 +/- 1%, P < 0.05; n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)