Interstitial Ca2+ undergoes dynamic changes sufficient to stimulate nerve-dependent Ca2+-induced relaxation

We recently described a perivascular sensory nerve-linked dilator system that can be activated by interstitial Ca2+ (Ca-isf(2+)). The present study tested the hypothesis that Ca-isf(2+) in the rat duodenal submucosa varies through a range that is sufficient to activate this pathway. An in situ microdialysis method was used to estimate Ca-isf(2+). When the duodenal lumen was perfused with Ca2+-free buffer, Ca-isf(2+) was 1.0 +/- 0.13 mmol/l. Ca-isf(2+) increased to 1.52 +/- 0.04, 1.78 +/- 0.10, and 1.89 +/- 0.1 when the lumen was perfused with buffer containing 3, 6, and 10 mmol/l Ca2+, respectively (P < 0.05). Ca-isf(2+) was 1.1 +/- 0.06 mmol/l in fasted animals and increased to 1.4 +/- 0.06 mmol/l in free-feeding rats (P < 0.05). Wire myography was used to study isometric tension responses of isolated mesenteric resistance arteries. Cumulative addition of extracellular Ca2+-relaxed serotonin- and methoxamine-precontracted arteries with half-maximal effective doses of 1.54 +/- 0.05 and 1.61 +/- 0.08 mmol/l, respectively (n = 5). These data show that duodenal Ca-isf(2+) undergoes dynamic changes over a range that activates the sensory nerve-linked dilator system and indicate that this system can link changes in local Ca2+ transport with alterations in regional resistance and organ blood flow.