Horm Metab Res 2014; 46(08): 561-567
DOI: 10.1055/s-0034-1370992
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Relationship of Angiotensinase and Vasopressinase Activities Between Hypothalamus, Heart, and Plasma in L-NAME-Treated WKY and SHR

A. B. Villarejo
1   Unit of Physiology, Department of Health Sciences, University of Jaén, Spain
,
I. Prieto
1   Unit of Physiology, Department of Health Sciences, University of Jaén, Spain
,
A. B. Segarra
1   Unit of Physiology, Department of Health Sciences, University of Jaén, Spain
,
I. Banegas
1   Unit of Physiology, Department of Health Sciences, University of Jaén, Spain
,
R. Wangensteen
1   Unit of Physiology, Department of Health Sciences, University of Jaén, Spain
,
F. Vives
2   Instituto de Neurociencia ‘Federico Oloriz’, University of Granada, Granada, Spain
,
M. de Gasparo
3   Cardiovascular & Metabolic Syndrome Adviser, Rossemaison, Switzerland
,
M. Ramírez-Sánchez
1   Unit of Physiology, Department of Health Sciences, University of Jaén, Spain
› Author Affiliations
Further Information

Publication History

received 21 November 2013

accepted 17 February 2014

Publication Date:
13 March 2014 (online)

Abstract

The renin-angiotensin system (RAS), vasopressin, and nitric oxide (NO) interact to regulate blood pressure at central and peripheral level. To improve our understanding of their interaction and their relationship with the hypothalamus and the cardiovascular system, we analyzed angiotensin- and vasopressin-metabolizing activities in hypothalamus (HT), left ventricle (LV), and plasma, collected from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) treated or not with L-NAME [N(G)-nitro-l-arginine methyl ester], which inhibits the formation of NO and over-activates the sympathetic nervous system. Previous observations in WKY suggested higher formation of Ang III and Ang IV in the HT and higher availability of Ang II in plasma after L-NAME treatment. Our current results show higher formation of Ang IV and higher metabolism of vasopressin after treatment with L-NAME in the LV of WKY rats. In SHR treated with L-NAME, there is higher availability of Ang III in the HT leading to higher release of vasopressin together with lower formation of Ang 2–10. In their LV, however, there is an increase of vasopressinase. Interestingly, while the enzymatic activities in the HT and LV of WKY rats and control SHR are poorly correlated, they are well but inversely correlated in the L-NAME treated SHR. On the other hand, no significant correlations between enzymatic activities in HT or LV and plasma were noticed. Our results suggest that eNOS inhibition in SHR induces or enhances an inverse reciprocal interaction between HT and LV involving the RAS and vasopressin, which may be mediated by the autonomic nervous system.

 
  • References

  • 1 Wright JW, Harding JW. The brain renin-angiotensin system: a diversity of functions and implications for CNS diseases. Pflugers Arch 2013; 465: 133-151
  • 2 Hupf H, Grimm D, Riegger GA, Schunkert H. Evidence for a vasopressin system in the rat heart. Circ Res 1999; 84: 365-370
  • 3 Segarra AB, Prieto I, Banegas I, Villarejo AB, Wangensteen R, de Gasparo M, Vives F, Ramírez-Sánchez M. The brain-heart connection: frontal cortex and left ventricle angiotensinase activities in control and captopril-treated hypertensive rats – a bilateral study. Int J Hypertens 2013; 2013 156179
  • 4 Bodineau L, Frugière A, Marc Y, Claperon C, Llorens-Cortes C. Aminopeptidase A inhibitors as centrally acting antihypertensive agents. Heart Fail Rev 2008; 13: 311-319
  • 5 Segarra AB, Ramírez M, Villarejo AB, Banegas I, Vives F, de Gasparo M, Alba F, Cobo J, Prieto I. Hypothalamic and plasmatic angiotensin metabolism in L-NAME treated rats. Horm Metab Res 2010; 42: 222-224
  • 6 Toni R, Malaguti A, Benfenati F, Martini L. The human hypothalamus: a morpho-functional perspective. J Endocrinol Invest 2004; 27: 73-94
  • 7 Ranson RN, Motawei K, Pyner S, Coote JH. The paraventricular nucleus of the hypothalamus sends efferents to the spinal cord of the rat that closely appose sympathetic preganglionic neurones projecting to the stellate ganglion. Exp Brain Res 1998; 120: 164-172
  • 8 Saeb-Parsy K, Lombardelli S, Khan FZ, McDowall K, Au-Yong IT, Dyball RE. Neural connections of hypothalamic neuroendocrine nuclei in the rat. J Neuroendocrinol 2000; 12: 635-648
  • 9 Scheer FA, Ter Horst GJ, van der Vliet J, Buijs RM. Physiological and anatomic evidence for regulation of the heart by suprachiasmatic nucleus in rats. Am J Physiol Heart Circ Physiol 2001; 280: H1391-H1399
  • 10 Vaseghi M, Zhou W, Shi J, Ajijola OA, Hadaya J, Shivkumar K, Mahajan A. Sympathetic innervation of the anterior left ventricular wall by the right and left stellate ganglia. Heart Rhythm 2012; 9: 1303-1309
  • 11 Török J. Participation of nitric oxide in different models of experimental hypertension. Physiol Res 2008; 57: 813-825
  • 12 Zhou X, Frohlich ED. Analogy of cardiac and renal complications in essential hypertension and aged SHR or L-NAME/SHR. Med Chem 2007; 3: 61-65
  • 13 Ramírez M, Prieto I, Alba F, Vives F, Banegas I, de Gasparo M. Role of central and peripheral aminopeptidase activities in the control of blood pressure: a working hypothesis. Heart Fail Rev 2008; 13: 339-353
  • 14 Stragier B, De Bundel D, Sarre S, Smolders I, Vauquelin G, Dupont A, Michotte Y, Vanderheyden P. Involvement of insulin-regulated aminopeptidase in the effects of the renin-angiotensin fragment angiotensin IV: a review. Heart Fail Rev 2008; 13: 321-337
  • 15 Villarejo AB, Segarra AB, Ramírez M, Banegas I, Wangensteen R, de Gasparo M, Cobo J, Alba F, Vives F, Prieto A. Angiotensinase and vasopressinase activities in hypothalamus, plasma, and kidney after inhibition of angiotensin-converting enzyme: basis for a new working hypothesis. Horm Metab Res 2012; 44: 152-154
  • 16 Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 4th ed. London: Academic Press; 1998
  • 17 Ramírez M, Prieto I, Banegas I, Segarra AB, Alba F. Neuropeptidases. Methods Mol Biol 2011; 789: 287-294
  • 18 Bradford MM. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem 1976; 72: 248-254
  • 19 Clarke GM, Kempson RE. Introduction to the design and analysis of experiments. London: Arnold; 1997
  • 20 Martinez DV, Rocha R, Matsumura M, Oestreicher E, Ochoa-Maya M, Roubsanthisuk W, Williams GH, Adler GK. Cardiac damage prevention by eplerenone: comparison with low sodium diet or potassium loading. Hypertension 2002; 39: 614-618
  • 21 Takemoto M, Egashira K, Usui M, Numaguchi K, Tomita H, Tsutsui H, Shimokawa H, Sueishi K, Takeshita A. Important role of tissue angiotensin-converting enzyme activity in the pathogenesis of coronary vascular and myocardial structural changes induced by long-term blockade of nitric oxide synthesis in rats. J Clin Invest 1997; 99: 278-287
  • 22 Kadekaro M. Nitric oxide modulation of the hypothalamo-neurohypophyseal system. Braz J Med Biol Res 2004; 37: 441-450
  • 23 Roesch DM, Blackburn-Munro RE, Verbalis JG. Mineralocorticoid treatment attenuates activation of oxytocinergic and vasopressinergic neurons by icv ANG II. Am J Physiol Regul Integr Comp Physiol 2001; 280: R1853-R1864
  • 24 van Acker SA, Oitzl MS, Fluttert MF, de Kloet ER. Centrally regulated blood pressure response to vasoactive peptides is modulated by corticosterone. J Neuroendocrinol 2002; 14: 56-63
  • 25 Ramírez-Sánchez M, Prieto I, Wangensteen R, Banegas I, Segarra AB, Villarejo AB, Vives F, Cobo J, de Gasparo M. The renin-angiotensin system: new insight into old therapies. Curr Med Chem 2013; 20: 1313-1322
  • 26 Vanderheyden PM. From angiotensin IV binding site to AT4 receptor. Mol Cell Endocrinol 2009; 302: 159-166
  • 27 Slinker BK, Wu Y, Brennan AJ, Campbell KB, Harding JW. Angiotensin IV has mixed effects on left ventricle systolic function and speeds relaxation. Cardiovasc Res 1999; 42: 660-669
  • 28 Dos Santos FM, Martins Dias DP, da Silva CA, Fazan Jr R, Salgado HC. Sympathetic activity is not increased in L-NAME hypertensive rats. Am J Physiol Regul Integr Comp Physiol 2010; 298: R89-R95
  • 29 Scrogin KE, Hatton DC, Chi Y, Luft FC. Chronic nitric oxide inhibition with L-NAME: effects on autonomic control of the cardiovascular system. Am J Physiol 1998; 274: R367-R374
  • 30 Taggart P, Critchley H, Lambiase PD. Heart-brain interactions in cardiac arrhythmia. Heart 2011; 97: 698-708
  • 31 Barret AJ, Rawlings ND, Woessner JF. Handbook of proteolytic enzymes. London: Academic Press; 1998
  • 32 Banegas I, Prieto I, Vives F, Alba F, de Gasparo M, Duran R, Luna Jde D, Segarra AB, Hermoso F, Ramírez M. Asymmetrical response of aminopeptidase A and nitric oxide in plasma of normotensive and hypertensive rats with experimental hemiparkinsonism. Neuropharmacology 2009; 56: 573-579
  • 33 Lanfear DE, Sabbah HN, Goldsmith SR, Greene SJ, Ambrosy AP, Fought AJ, Kwasny MJ, Swedberg K, Yancy CW, Konstam MA, Maggioni AP, Zannad F, Gheorghiade M. EVEREST trial investigators. Association of arginine vasopressin levels with outcomes and the effect of V2 blockade in patients hospitalized for heart failure with reduced ejection fraction: insights from the EVEREST trial. Circ Heart Fail 2013; 6: 47-52