Abstract
Hypertension has been described as an important risk factor for cardiovascular morbidity and mortality, despite current treatments. Therefore an increased understanding of the mechanisms in the development of hypertension has become essential. This project involves the study of the vascular component of murine models of hypertension. Firstly the protective role of calcitonin gene-related peptide (CGRP)-like peptide adrenomedullin (AM) was examined using transgenic mice for the AM receptor. Secondly transient receptor potential vanilloid 1 (TRPV1) was studied, activation of which is known to release the sensory neuropeptide CGRP.The angiotensin II (ATII) induced hypertension murine model is considered to mimic essential hypertension. Here, hypertension was induced in 3-4 month old mice (mixed gender) over 14 days following implantation of ATII-containing osmotic mini-pumps. Blood pressure was monitored before mini-pump implantation and until day 14 by either tail cuff plethysmography or telemetry. Post-hoc study analysis of vascular hypertrophy and vascular dysfunction biomarkers (e.g. VCAM-1 and endothelin) was performed. Studies in AM receptor transgenic mice revealed no effect on hypertension, but significant protection against aortic vascular remodelling. This indicates that adrenomedullin, like CGRP, is a protective peptide in the vasculature. Surprizingly, the TRPV1 KO mice were protected against hypertension and aortic remodelling, suggesting a lack of critical involvement of CGRP.
| Date of Award | 2014 |
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| Original language | English |
| Awarding Institution |
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