JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on December 2, 2005; DOI: 10.1124/jpet.105.092783

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.105.092783v1
316/3/1269    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhao, Y.
Right arrow Articles by McDermott, B. J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, Y.
Right arrow Articles by McDermott, B. J


Received for publication July 18, 2005.
Revised November 23, 2005.
Accepted for publication November 30, 2005.

Differential expression of components of the cardiomyocyte adrenomedullin / intermedin receptor system following blood pressure reduction in NO-deficient hypertension

YouYou Zhao 1, David Bell 1*, Lisa R Smith 1, Li Zhao 1, Adrian B Devine 1, Eugene M McHenry 1, D Paul Nicholls 2, Barbara J McDermott 1

1 The Queen's University of Belfast 2 Royal Victoria Hospital Belfast

* Address correspondence to: E-mail: d.bell{at}qub.ac.uk

Abstract

Adrenomedullin (AM) and intermedin (IMD, adrenomedulln-2) are vasodilator peptides related to calcitonin-gene related peptide (CGRP). The actions of these peptides are mediated by the calcitonin receptor-like receptor (CLR) in association with one of three receptor activity modifying proteins. CGRP is selective for CLR/RAMP1, AM for CLR/RAMP2 and 3, and IMD acts at both CGRP and AM receptors. In a model of pressure overload induced by inhibition of nitric oxide synthase (NOS), up-regulation of AM was observed previously in cardiomyocytes demonstrating a hypertrophic phenotype. The current objective was to examine the effects of blood pressure reduction on cardiomyocyte expression of AM and IMD and their receptor components. L-NAME (35mg/kg/day) was administered to rats for 8 weeks, with or without concurrent administration of hydralazine (50mg/kg/day) and hydrochlorothiazide (7.5mg/kg/day). In left ventricular cardiomyocytes from L-NAME treated rats, increases (-fold) in mRNA expression were 1.6 (preproAM), 8.4 (preproIMD), 3.4 (CLR), 4.1 (RAMP1), 2.8 (RAMP2) and 4.4 (RAMP3). Hydralazine / hydrochlorothiazide normalised systolic BP and abolished mRNA up-regulation of hypertrophic markers, sk-{alpha}-actin and BNP and of preproAM, CLR, RAMP2 and RAMP3 but did not normalise cardiomyocyte width nor preproIMD or RAMP1 mRNA expression. The robust increase in IMD expression indicates an important role for this peptide in the cardiac pathology of this model but, unlike AM, IMD is not associated with pressure overload upon the myocardium. The concordance of IMD and RAMP1 up-regulation indicates a CGRP-type receptor action; considering also a lack of response to BP reduction, IMD may, like CGRP, have an anti-ischemic function.


Key words: adrenomedullin, cardiomyocyte, hypertrophy, intermedin, nitric oxide, receptor


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
A. R. Allen, E. J. Kelso, D. Bell, Y. Zhao, P. Dickson, and B. J. McDermott
Modulation of Contractile Function through Neuropeptide Y Receptors during Development of Cardiomyocyte Hypertrophy
J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1286 - 1296.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
F. Dong, M. M. Taylor, W. K. Samson, and J. Ren
Intermedin (adrenomedullin-2) enhances cardiac contractile function via a protein kinase C- and protein kinase A-dependent pathway in murine ventricular myocytes
J Appl Physiol, September 1, 2006; 101(3): 778 - 784.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Rahman, A. Nishiyama, P. Guo, Y. Nagai, G.-X. Zhang, Y. Fujisawa, Y.-Y. Fan, S. Kimura, N. Hosomi, K. Omori, et al.
Effects of Adrenomedullin on Cardiac Oxidative Stress and Collagen Accumulation in Aldosterone-Dependent Malignant Hypertensive Rats
J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1323 - 1329.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2005 by the American Society for Pharmacology and Experimental Therapeutics.