Peptides 26 (2005) 691–700 Distribution of atrial natriuretic peptide and its effects on contraction and intracellular calcium in ventricular myocytes from streptozotocin-induced diabetic rat F.C. Howarth a,∗ , A. Adem a , E.A. Adeghate a , N.A. Al Ali a , A.M. Al Bastaki a , F.R. Sorour a , R.O. Hammoudi a , N.A. Ghaleb a , N.J. Chandler b , H. Dobrzynski b a Department of Physiology, Faculty of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, U.A.E. b School of Biomedical Sciences, University of Leeds, Leeds, UK Received 19 September 2004; received in revised form 30 November 2004; accepted 2 December 2004 Available online 11 January 2005 Abstract The distribution of atrial natriuretic peptide (ANP) in blood plasma and cardiac muscle and its effects on ventricular myocyte contraction and intracellular free calcium concentration [Ca 2+ ] i in the streptozotocin (STZ)-induced diabetic rat have been investigated. Blood plasma concentration and heart atrial and ventricular contents of ANP were significantly increased in STZ-treated rats compared to age-matched controls. STZ treatment increased the number of ventricular myocytes immunolabeled with antibodies against ANP. In control myocytes the percentage of cells that labeled positively and negatively were 17% versus 83%, respectively. However, in myocytes from STZ-treated rat the percentages were 52% versus 53%. Time to peak (TPK) shortening was significantly and characteristically prolonged in myocytes from STZ-treated rats (360 ± 5 ms) compared to controls (305 ± 5 ms). Amplitude of the Ca 2+ transient was significantly increased in myocytes from STZ-treated rats compared to controls (0.39 ± 0.02 versus 0.29 ± 0.02 fura-2 RU in controls) and treatment with ANP reduced the amplitude of the Ca 2+ transient to control levels. ANP may have a protective role in STZ-induced diabetic rat heart. © 2004 Elsevier Inc. All rights reserved. Keywords: Atrial natriuretic peptide; Diabetes; Ventricular myocytes; Calcium 1. Introduction Atrial natriuretic peptide (ANP) is a hormone which is released predominantly by atrial myocytes in response to atrial wall stretch [8]. In the normal healthy adult heart ANP is mainly synthesized in atrial granules as a larger molecular weight precursor which is believed to be rapidly converted to an active peptide during or shortly after secretion [32]. Levels of ANP are increased during experimental hypoxia and in various disease states including hypertension, coronary heart failure, myocardial infarction and diabetes ∗ Corresponding author. Tel.: +971 3 7039536; fax: +971 3 7671966. E-mail address: chris.howarth@uaeu.ac.ae (F.C. Howarth). [16,28]. ANP induces relaxation of vascular smooth muscle, decreases blood pressure and cardiac output and these actions are associated with inhibition of aldosterone, renin and vasopressin release [1]. Ventricular hypertrophy is characterized by an augmentation of the synthesis and release of ANP from the ventricles [17]. Treatment of young adult rats with streptozotocin (STZ) causes damage to pancreatic -cells, hypoinsulinemia and an associated hyperglycemia features which are frequently observed in clinical type 1 diabetes [9]. The remodeling of distribution of ANP in both atrial and ventricular myocytes and the effects of ANP on ventricular myocyte contraction and [Ca 2+ ] i in the STZ-induced diabetic rat have been investigated in this study. 0196-9781/$ – see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.peptides.2004.12.003