Role of cerebellar adrenomedullin in blood pressure regulation.

摘要: Adrenomedullin (AM) and their receptor components, calcitonin-receptor-like (CRLR) activity-modifying protein (RAMP1, RMP2 RAMP3) are widely expressed in the central nervous system, including cerebellum. We have shown that AM binding sites altered cerebellum during hypertension, suggesting a role for cerebellar adrenomedullinergic system blood pressure regulation. To further evaluate of cerebellum, we assessed expression AM, RAMP1, RAMP2, RAMP3 CRLR vermis 8 16week old spontaneously hypertensive (SHR) normotensive Wistar Kyoto (WKY) rats. In addition, effect microinjection into rat on arterial (BP) was determined. Animals were sacrificed by decapitation dissected quantification CRLR, RAMP2 using western blot analysis. Another group male, SHR WKY rats anesthetized, cannula implanted vermis. Following recovery (0.02 to 200pmol/5μL) or vehicle injected BP determined, before after treatments, non-invasive plethysmography. establish subtype involved action vivo, animals received microinjections AM22-52 (200pmol/5μL), an AM1 antagonist, CGRP1 CGRP8-37 (200pmol/5μL) vermis, administered simultaneously with microinjection. Cannulation verified post mortem situ injection dye solution. Our findings demonstrated RAMP1 higher rats, while lower than those both vivo caused profound, dose dependent, hypotensive but not Coinjections putative abolished decreases mean (MAP) evoked showing acts through its reduce MAP. These demonstrate dysregulation AM-system suggest plays important regulation BP. Likewise; they constitute novel mechanism control which has been described so far.