Atrial natriuretic peptide (ANP) is produced and released by mammalian cardiomyocytes and induces natriuresis, diuresis, and lowering of blood pressure. The present study examined localization of ANP and a possible role of the hypothalamic-pituitary-adrenal axis (HPA) activity on the expression of proANP gene in the heart. The Sprague Dawley (SD) and Lewis (LE) rat strains were used. The animals were exposed to the two types of stress: immobilization and immobilization combined with water immersion for 1 hour. Localization of ANP was detected by immunohistochemistry and expression of the proANP mRNA by real-time qPCR in all heart compartments of control and stressed animals after 1 and 3 hours after stress termination (IS1, IS3, ICS1, and ICS3). Relatively high density of ANP-immunoreactivity was observed in both atria of both rat strains. In control rats of both strains, the expression of the proANP mRNA was higher in the atria than in ventricles. In SD rats with the intact HPA axis, an upregulation of ANP gene expression was observed in the right atrium after IS1, in both atria and the left ventricle after IS3 and in the left atrium and the left ventricle after ICS3. In LE rats with a blunted reactivity of the HPA axis, no increase or even a downregulation of the gene expression was observed. Thus, acute stress-induced increase in the expression of the proANP gene is related to the activity of the HPA axis. It may have relevance to ANP-induced protection of the heart.

2nd Department of Internal Medicine Faculty of Medicine Comenius University and University Hospital Bratislava Slovakia

Department of Chemical Drugs Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno Czech Republic

Department of Physiology Charles University Prague Faculty of Medicine in PilsenPilsen Czech Republic; Biomedical Centre Charles University Prague Faculty of Medicine in PilsenPilsen Czech Republic

Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine and General University Hospital Charles University Prague Czech Republic

See more in PubMed

Nakao K, Ogawa Y, Suga S, Imura H. Molecular biology and biochemistry of the natriuretic peptide system. I: Natriuretic peptides. J Hypertens. 1992;10:907–912. PubMed

Potter LR, Yoder AR, Flora DR, Antos LK, Dickey DM. Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications. Handb Exp Pharmacol. 2009;191:341–366. PubMed PMC

Edwards BS, Zimmerman RS, Schwab TR, Heublein DM, Burnett JC Jr. Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor. Circ Res. 1988;62:191–195. PubMed

McGrath MF, de Bold AJ. Determinants of natriuretic peptide gene expression. Peptides. 2005;26:933–943. PubMed

Schlueter N, de Sterke A, Willmes DM, Spranger J, Jordan J, Birkenfeld AL. Metabolic actions of natriuretic peptides and therapeutic potential in the metabolic syndrome. Pharmacol Ther. 2014;144:12–27. PubMed

McGrath MF, de Bold ML, de Bold AJ. The endocrine function of the heart. Trends Endocrinol Metab. 2005;16:469–477. PubMed

Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002;53:865–871. PubMed

Koob GF. Corticotropin-releasing factor, norepinephrine, and stress. Biol Psychiatry. 1999;46:1167–1180. PubMed

Dalack GW, Roose SP. Perspectives on the relationship between cardiovascular disease and affective disorder. J Clin Psychiatry. 1990;51:4–11. PubMed

Hatton DC, Brooks V, Qi Y, McCarron DA. Cardiovascular response to stress: baroreflex resetting and hemodynamics. Am J Physiol. 1997;272:R1588–1594. PubMed

Grabie N, Hsieh DT, Buono C, Westrich JR, Allen JA, Pang H, Stavrakis G, Lichtman AH. Neutrophils sustain pathogenic CD8+ T cell responses in the heart. Am J Pathol. 2003;163:2413–2420. PubMed PMC

Tavener SA, Kubes P. Cellular and molecular mechanisms underlying LPS-associated myocyte impairment. Am J Physiol Heart Circ Physiol. 2006;290:H800–806. PubMed

Ueyama T, Senba E, Kasamatsu K, Hano T, Yamamoto K, Nishio I, Tsuruo Y, Yoshida K. Molecular mechanism of emotional stress-induced and catecholamine-induced heart attack. J Cardiovasc Pharmacol. 2003;41:S115–118. PubMed

Ueyama T. Emotional stress-induced Tako-tsubo cardiomyopathy: animal model and molecular mechanism. Ann N Y Acad Sci. 2004;1018:437–444. PubMed

Wann BP, Audet MC, Gibb J, Anisman H. Anhedonia and altered cardiac atrial natriuretic peptide following chronic stressor and endotoxin treatment in mice. Psychoneuroendocrinology. 2010;35:233–240. PubMed

Gomez F, De Kloet ER, Armario A. Glucocorticoid negative feedback on the HPA axis in five inbred rat strains. Am J Physiol. 1998;274:R420–427. PubMed

Klenerova V, Kaminsky O, Sida P, Krejci I, Hlinak Z, Hynie S. Impaired passive avoidance acquisition in Sprague-Dawley and Lewis rats after restraint and cold stress. Behav Brain Res. 2002;136:21–29. PubMed

Skopek P, Hynie S, Chottova-Dvorakova M, Sida P, Slavikova J, Mistrova E, Klenerova V. Effects of acute stressors on the expression of oxytocin receptor mRNA in hearts of rats with different activity of HPA axis. Neuro Endocrinol Lett. 2012;33:124–132. PubMed

Pfaffl MW, Tichopad A, Prgomet C, Neuvians TP. Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper--Excel-based tool using pair-wise correlations. Biotechnol Lett. 2004;26:509–515. PubMed

de Bold AJ. On the shoulders of giants: the discovery of atrial natriuretic factor. Can J Physiol Pharmacol. 1987;65:2007–2012. PubMed

Vesely DL, San Miguel GI, Hassan I, Schocken DD. Atrial natriuretic hormone, vessel dilator, long-acting natriuretic hormone, and kaliuretic hormone decrease the circulating concentrations of CRH, corticotropin, and cortisol. J Clin Endocrinol Metab. 2001;86:4244–4249. PubMed

Piechota M, Banach M, Jacon A, Rysz J. Natriuretic peptides in cardiovascular diseases. Cell Mol Biol Lett. 2008;13:155–181. PubMed PMC

Ogawa T, Linz W, Stevenson M, Bruneau BG, Kuroski de Bold ML, Chen JH, Eid H, Scholkens BA, de Bold AJ. Evidence for load-dependent and load-independent determinants of cardiac natriuretic peptide production. Circulation. 1996;93:2059–2067. PubMed

Ruskoaho H. Cardiac hormones as diagnostic tools in heart failure. Endocr Rev. 2003;24:341–356. PubMed

Franci CR, Anselmo-Franci JA, McCann SM. The role of endogenous atrial natriuretic peptide in resting and stress-induced release of corticotropin, prolactin, growth hormone, and thyroid-stimulating hormone. Proc Natl Acad Sci U S A. 1992;89:11391–11395. PubMed PMC

Buynitsky T, Mostofsky DI. Restraint stress in biobehavioral research: Recent developments. Neurosci Biobehav Rev. 2009;33:1089–1098. PubMed

Kvetnansky R, McCarty R, Thoa NB, Lake CR, Kopin IJ. Sympatho-adrenal responses of spontaneously hypertensive rats to immobilization stress. Am J Physiol. 1979;236:H457–462. PubMed

Espiner EA. The effects of stress on salt and water balance. Baillieres Clin Endocrinol Metab. 1987;1:375–390. PubMed

Fink G, Dow RC, Casley D, Johnston CI, Bennie J, Carroll S, Dick H. Atrial natriuretic peptide is involved in the ACTH response to stress and glucocorticoid negative feedback in the rat. J Endocrinol. 1992;135:37–43. PubMed

Mangat H, de Bold AJ. Stretch-induced atrial natriuretic factor release utilizes a rapidly depleting pool of newly synthesized hormone. Endocrinology. 1993;133:1398–1403. PubMed

Saito Y, Nakao K, Nishimura K, Sugawara A, Okumura K, Obata K, Sonoda R, Ban T, Yasue H, Imura H. Clinical application of atrial natriuretic polypeptide in patients with congestive heart failure: beneficial effects on left ventricular function. Circulation. 1987;76:115–124. PubMed

Yoshimura M, Yasue H, Morita E, Sakaino N, Jougasaki M, Kurose M, Mukoyama M, Saito Y, Nakao K, Imura H. Hemodynamic, renal, and hormonal responses to brain natriuretic peptide infusion in patients with congestive heart failure. Circulation. 1991;84:1581–1588. PubMed

Sternberg EM, Glowa JR, Smith MA, Calogero AE, Listwak SJ, Aksentijevich S, Chrousos GP, Wiilder RL, Gold PW. Corticotropin releasing hormone related behavioral and neuroendocrine responses to stress in Lewis and Fischer rats. Brain Res. 1992;570:54–60. PubMed

de Bold AJ, Bruneau BG, Kuroski de Bold ML. Mechanical and neuroendocrine regulation of the endocrine heart. Cardiovasc Res. 1996;31:7–18. PubMed

Bianciotti LG, De Bold AJ. Effect of selective ET(A) receptor blockade on natriuretic peptide gene expression in DOCA-salt hypertension. Am J Physiol Heart Circ Physiol. 2000;279:H93–H101. PubMed

Bianciotti LG, de Bold AJ. Modulation of cardiac natriuretic peptide gene expression following endothelin type A receptor blockade in renovascular hypertension. Cardiovasc Res. 2001;49:808–816. PubMed

Ballermann BJ, Bloch KD, Seidman JG, Brenner BM. Atrial natriuretic peptide transcription, secretion, and glomerular receptor activity during mineralocorticoid escape in the rat. J Clin Invest. 1986;78:840–843. PubMed PMC

Kuwahara K, Nakao K. Regulation and significance of atrial and brain natriuretic peptides as cardiac hormones. Endocr J. 2010;57:555–565. PubMed

Gardner DG, Gertz BJ, Deschepper CF, Kim DY. Gene for the rat atrial natriuretic peptide is regulated by glucocorticoids in vitro. J Clin Invest. 1988;82:1275–1281. PubMed PMC

Mizukami Y, Yoshioka K, Morimoto S, Yoshida K. A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion. J Biol Chem. 1997;272:16657–16662. PubMed

Mizukami Y, Yoshida K. Mitogen-activated protein kinase translocates to the nucleus during ischaemia and is activated during reperfusion. Biochem J. 1997;323:785–790. PubMed PMC

Substance P Receptor in the Rat Heart and Regulation of Its Expression in Long-Term Diabetes

The Effect of Acute and Repeated Stress on CRH-R1 and CRH-R2 mRNA Expression in Pituitaries of Wild Type and CRH Knock-Out Mice