Extracellular calcium and vascular responses after forearm ischemia.
BACKGROUND: The myogenic response is a phenomenon in which blood vessels respond to increases and decreases in transmural pressure with constriction and dilation, respectively. Despite intense investigation into the signaling mechanisms underlying this response, the precise mechanisms remain unclear. It has been suggested that the myogenic response occurs when pressure or stretch evokes increases in vessel wall tension that results in vessel smooth muscle cell depolarization. This causes Ca2+ entry through voltage-gated Ca2+ channels. Of note, in vitro studies demonstrate that the magnitude of the myogenic response is dependent on the extracellular Ca2+. We tested the hypothesis that in conscious humans, physiological changes in extracellular Ca2+ concentrations would be an important determinant of the myogenic response. METHODS AND RESULTS: Venous blood ionized calcium was used as an index of interstitial calcium and was measured 5, 15, and then every 15 seconds for 75 seconds, then every 30 seconds for 90 seconds, then finally at the 300-second mark. Forearm blood pressure and flow velocity were determined after 10 minutes of forearm ischemia. We found that the rate of change in serum calcium levels varied as a function of transmural pressure (r=0.96). Moreover, the calcium concentration was inversely proportional to forearm blood velocity (r=0.99). CONCLUSIONS: We hypothesize that muscle stretch caused by a rise in transmural pressure raises interstitial calcium by unknown mechanisms and this in turn acts to lower limb flow velocity.