Prolonged calcium activation by an endogenous factor released from the hind limb of ischemic rats

The hypothesis was tested that an endogenous factor released from ischémie hind limbs increases the sensitivity of calcium channels, thus contributing to increased vascular smooth muscle contractility and hypertension. Hindlimb ischemia was generated in rats by infrarenal aortic cross-clamping for 5 hours, after which plasma was obtained from femoral vein blood. Incubating naive aortic rings (endothelium removed) for 2h in plasma collected from ischémie rats demonstrated a significant decrease in the concentration of Bay K 8644 necessary to produce a threshold response and half maximal response when compared to those of control rats. The washout curve for contraction in response to phenylephrine was not significantly altered by ischémie plasma incubation. However, when rings were incubated in ischémie plasma, the washout curve, after application of Bay K 8644, in either a calcium enriched or calcium free solution, was singificamly prolonged. These results suggest a factor in the ischémie plasma that specifically alters the response of calcium channels to Bay K 8644. This prolonged increase in the sensitivity to the calcium channel agonist, Bay K 8644 suggests that an endogenous factor from the ischémie hindlimb may contribute to hypertension in the setting of peripheral ischemia. Incubation Force after 30 min. wash Force after 60 min. wash of Bay K 8644, % initial of Bay K 8644, % initial Ischémie 83 ±7* 71±8* Control 45 ±9 25 ±6.