Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.487590
Title: Differential-influence of hypertension and oxidative stress on the adrenomedullin / intermedin receptor system in cardiomyocyte hypertrophy
Author: Zhao, Y. Y.
Awarding Body: Queens -Belfast
Current Institution: Queen's University Belfast
Date of Award: 2008
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Abstract:
Reactive oxygen species (ROS) contribute to hypertension and development of left ventricular. hypertrophy (LVH). ROS are also implicated in potentially counterbalancing processes, through stimulation of oxygen-sensitive gene expression. The vasodilator substance, adrenomedullin (AM), a member of the calcitonin gene-related peptide (CORP) family, is upregulated under conditions of oxidative stress and can attenuate ventricular remodelling. The purpose of this . study was to compare AM and the newly discovered and structurally-related peptide, intermedin (IMD), along with the associated CL receptor and receptor activity modifying proteins (RAMPS 1-3), focusing on processes contributing to their upregulation in ventricular cardiomyocytes. Two appropriate experimental models were used: the spontaneously hypertensive rat (SHR), which exhibits compensated LVH at 20 weeks of age; the Sprague-Dawley rat made. hypertensive by treatment with the NO synthase inhibitor, Nro-nitro-L-arginine methyl ester (LNAME), which develops LVH by 16 weeks of age. Robust increases in IMD mRNA expression, greater than those' that of AM, were observed in both SHRs and L-NAME treated rats, suggesting a important role for IMD in myocardial remodelling. In the L-NAME model, which exhibited more significant myocyte hypertrophy and oxidative stress, effects of blood pressure lowering using hydralazine / hydrochlorothiazide, antioxidant therapy with vitamin C / Tempol, and treatment with nifedipine I atenolQl to target hypertension and ischemic insult were assessed. These studies demonstrated that upregulation ofIMD at1d RAMP 1 occurs mainly as a result of oxidative stress, whereas AM and RAMPs 2 and 3 are induced by 'pressure overload. Similar to AM, IMD had' a direct antihypertrophic action in vitro and upregulated IMD could therefore counter-regulate hypertrophy in vivo, possibly through increased AM receptors, viz. the CL-rec.eptor with RAMP 2 and/or 3. The concordance of IMD and RAMP-l upregulation indicates, a CORP-type receptor action; considering also a lack of response to blood pressure reduction alone, IMD may possibly, as does CORP, serve primarily an anti-ischemic function.
Supervisor: Not available Sponsor: Not available
Qualification Name: Queens -Belfast, 2008 Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.487590  DOI: Not available
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