The experiments in this proposal are based on the hypothesis that low serum ionized calcium decreases the synthesis of CGRP, which is a vasodilator, and by reducing that vasodilator, the level of blood pressure rises and contributes to hypertension. Secondly, the change in 1,25-vitamin D3 modulates neuronal CGRP synthesis such that increasing 1,25-D decreases CGRP neuronal content. This hypothesis is based on a current hypothesis that low calcium contributes to hypertension and offers a mechanism for this finding. Preliminary work by the investigator and his co-workers have demonstrated immunocytochemical distribution of CGRP in the spinal cord of rats. The levels of staining increase with increasing calcium diet. To test this more thoroughly, Dr. Dipette proposes to first infuse calcium chloride i.v. and measure the levels of immunocytochemical CGRP content in the spinal cord. Secondly, EGTA will be infused to reduce the levels of calcium. Third, CGRP mRNA levels will be measured in the dorsal root ganglia following chronic administration of 1,25-D. It is hypothesized that the changes in CGRP neuronal content, in response to dietary calcium increases, are due to changes in synthesis and release, rather than in storage. To test this, they will quantify CGRP mRNA by dot blot analysis and immunocytochemistry. The studies will be carried out in normotensive animals and in DOCA-salt rats to test the hypothesis that CGRP is more sensitive in low renin sodium dependent hypertension.
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