Use this URL to cite or link to this record in EThOS:
Title: Differential-influence of hypertension and oxidative stress on the adrenomedullin / intermedin receptor system in cardiomyocyte hypertrophy
Author: Zhao, Y. Y.
ISNI:       0000 0001 3577 5525
Awarding Body: Queens -Belfast
Current Institution: Queen's University Belfast
Date of Award: 2008
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
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:  DOI: Not available