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)
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Department of Internal Medicine, University of Texas Medical Branch, Galveston Island 77555, USA.
Bukoski
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D000818:Animals; D002118:Calcium / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D018999:Charybdotoxin; D005110:Extracellular Space / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D026902:Potassium Channel Blockers; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; D013729:Terpenes; D018999:Charybdotoxin; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium; D009638:Norepinephrine