Role of CGRP in Two Kidney One Clip Hypertension

Recently, the role of capsaicin-sensitive sensory nerves in two-kidney, one-clip (2K1C) renovascular hypertension has been investigated (24). Systolic blood pressure (measured by the tail-cuff method) was significantly elevated approx 25% in the 2K1C group compared to control rats 10 d following the initiation of the protocol. Treatment with capsaicin, which selectively depletes neuropeptides in sensory nerves, enhanced the hypertensive response to the procedure by another 20% at the same time period. A second injection of capsaicin produced an additional 25% increase in systolic blood pressure compared to the rats that had received a single injection at the second time point (30 d postoperative). The expression of a-CGRP mRNA in DRG, the level of CGRP in the plasma, and the density of CGRP immunoreactive fibers in mesenteric artery were all significantly increased in the 2K1C rats compared to the sham-operated controls. Treatment with capsaicin prevented the increase in CGRP expression in the hypertensive rats. Based on these results the authors concluded that in this model of renovascular hypertension the activity of capsaicin-sensitive sensory nerves is increased, via an upregulation of a-CGRP synthesis and release, as a compensatory response to partially counteract the increase in blood pressure.

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