Skip to main content
SpringerLink
Log in

Chronic captopril treatment reveals the role of ANG II in cardiovascular function of embryonic American alligators (Alligator mississippiensis)

  • Original Paper
  • Published:
Journal of Comparative Physiology B Aims and scope Submit manuscript

Abstract

Angiotensin II (ANG II) is a powerful vasoconstrictor of the renin–angiotensin system (RAS) that plays an important role in cardiovascular regulation in adult and developing vertebrates. Knowledge of ANG II’s contribution to developmental cardiovascular function comes from studies in fetal mammals and embryonic chickens. This is the first study to examine the role of ANG II in cardiovascular control in an embryonic reptile, the American alligator (Alligator mississippiensis). Using chronic low (~ 5-mg kg embryo−1), or high doses (~ 450-mg kg embryo−1) of captopril, an angiotensin-converting enzyme (ACE) inhibitor, we disrupted the RAS and examined the influence of ANG II in cardiovascular function at 90% of embryonic development. Compared to embryos injected with saline, mean arterial pressure (MAP) was significantly reduced by 41 and 72% under low- and high-dose captopril treatments, respectively, a greater decrease in MAP than observed in other developing vertebrates following ACE inhibition. Acute exogenous ANG II injection produced a stronger hypertensive response in low-dose captopril-treated embryos compared to saline injection embryos. However, ACE inhibition with the low dose of captopril did not change adrenergic tone, and the ANG II response did not include an α-adrenergic component. Despite decreased MAP that caused a left shifted baroreflex curve for low-dose captopril embryos, ANG II did not influence baroreflex sensitivity. This study demonstrates that ANG II contributes to cardiovascular function in a developing reptile, and that the RAS contributes to arterial blood pressure maintenance during development across multiple vertebrate groups.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Altimiras J, Franklin CE, Axelsson M (1998) Relationships between blood pressure and heart rate in the saltwater crocodile Crocodylus porosus. J Exp Biol 201(15):2235–2242

    PubMed  CAS  Google Scholar 

  • Berger PJ, Evans BK, Smith DG (1980) Localization of baroreceptors and gain of the baroreceptor-heart rate reflex in the lizard Trachydosaurus Rugosus. J Exp Biol 86(1):197–209

    Google Scholar 

  • Bottari SP, de Gasparo M, Steckelings UM, Levens NR (1993) Angiotensin II receptor subtypes: characterization, signalling mechanisms, and possible physiological implications. Front Neuroendocrin 14(2):123–171

    Article  CAS  Google Scholar 

  • Brooks VL, Reid IA (1986) Interaction between angiotensin II and the baroreceptor reflex in the control of adrenocorticotropic hormone secretion and heart rate in conscious dogs. Circ Res 58(6):816–828

    Article  PubMed  CAS  Google Scholar 

  • Brown SR, Stevens GA, Todt MJ (1983) Systemic and renal effects of angiotensin II in the freshwater turtle Pseudemys scripta elegans. Am J Physiol Reg Int Comp Physiol 245(6):R837–R842

    Article  Google Scholar 

  • Crossley DA II, Burggren WW, Altimiras J (2003a) Cardiovascular regulation during hypoxia in embryos of the domestic chicken Gallus gallus. Am J Physiol Regul Integr Comp Physiol 284(1):R219-226

    Article  Google Scholar 

  • Crossley DA II, Hicks JW, Altimiras J (2003b) Ontogeny of baroreflex control in the American alligator Alligator mississippiensis. J Exp Biol 206(16):2895–2902

    Article  PubMed  Google Scholar 

  • Crossley DA II, Hicks JW, Altimiras J (2003c) Ontogeny of baroreflex control in the American alligator Alligator mississippiensis. J Exp Biol 206:2895–2902

    Article  PubMed  Google Scholar 

  • Crossley DA II, Altimiras J (2005) Cardiovascular development in embryos of the American alligator Alligator mississippiensis: effects of chronic and acute hypoxia. J Exp Biol 208(Pt 1):31–39

    Article  PubMed  Google Scholar 

  • Crossley DA II, Burggren WW (2009) Development of cardiac form and function in ectothermic sauropsids. J Morphol 270(11):1400–1412

    Article  PubMed  Google Scholar 

  • Crossley D II, Jonker S, Hicks J, Thornburg K (2010) Maturation of the angiotensin II cardiovascular response in the embryonic White Leghorn chicken (Gallus gallus). J Comp Physiol B 180(7):1057–1065

    Article  PubMed  PubMed Central  Google Scholar 

  • Crossley DA II, Altimiras J (2012) Effect of selection for commercially productive traits on the plasticity of cardiovascular regulation in chicken breeds during embryonic development. Poult Sci 91(10):2628–2636

    Article  PubMed  Google Scholar 

  • Daïkha-Dahmane F, Levy-Beff E, Jugie M, Lenclen R (2006) Foetal kidney maldevelopment in maternal use of angiotensin II type I receptor antagonists. Pediatr Nephrol 21(5):729–732

    Article  PubMed  Google Scholar 

  • Deeming DC, Ferguson MWJ (1989) Effects of incubation temperature on growth and development of embryos of Alligator mississippiensis. J Comp Physiol B 159:183–193

    Article  Google Scholar 

  • Dendorfer A, Thornagel A, Raasch W, Grisk O, Tempel K, Dominiak P (2002) Angiotensin II induces catecholamine release by direct ganglionic excitation. Hypertension 40(3):348–354

    Article  PubMed  CAS  Google Scholar 

  • Düsing R, Kayser G, Wagner S, Scherf H, Glänzer K, Predel H-G, Kramer HJ (1987) Baroreflex setting and sensitivity in normal subjects: effects of pharmacologic inhibition of the angiotensin I converting enzyme. Am J Cardiol 59(10):D50–D54

    Article  Google Scholar 

  • Eme J, Altimiras J, Hicks JW, Crossley DA II (2011a) Hypoxic alligator embryos: chronic hypoxia, catecholamine levels and autonomic responses of in ovo alligators. Comp Biochem Physiol A 160(3):412–420

    Article  CAS  Google Scholar 

  • Eme J, Crossley DA, Hicks JW (2011b) Role of the left aortic arch and blood flows in embryonic American alligator (Alligator mississippiensis). J Comp Physiol B 181(3):391–401

    Article  PubMed  Google Scholar 

  • Eme J, Hicks JW, Crossley DA II (2011c) Chronic hypoxic incubation blunts a cardiovascular reflex loop in embryonic American alligator (Alligator mississippiensis). J Comp Physiol B 181(7):981–990

    Article  PubMed  CAS  Google Scholar 

  • Eme J, Rhen T, Tate K, Gruchalla K, Kohl Z, Slay C, Crossley DA II (2013) Plasticity of cardiovascular function in snapping turtle embryos (Chelydra serpentina): chronic hypoxia alters autonomic regulation and gene expression. Am J Physiol Reg Int Comp Physiol 304:R966–R979

    Article  CAS  Google Scholar 

  • Esteves CA, Burckhardt PL, Breno MC (2012) Presence of functional angiotensin II receptor and angiotensin converting enzyme in the aorta of the snake Bothrops jararaca. Life Sci 91(19–20):944–950

    Article  PubMed  CAS  Google Scholar 

  • Farrell DM, Wei C-C, Tallaj J, Ardell JL, Armour JA, Hageman GR, Bradley WE, Dell’Italia LJ (2001) Angiotensin II modulates catecholamine release into interstitial fluid of canine myocardium in vivo. Am J Physiol Heart Circ Physiol 281(2):H813–H822

    Article  PubMed  CAS  Google Scholar 

  • Ferguson MWJ (1985) Reproductive biology and embryology of the crocodilians. In: Gans C, Billet F, Maderson P (eds) Biology of the reptilia, vol 14. Wiley, New York, pp 329–491

    Google Scholar 

  • Friberg P, Sundelin B, Bohman S-O, Bobik A, Nilsson H, Wickman A, Gustafsson H, Petersen J et al (1994) Renin–angiotensin system in neonatal rats: induction of a renal abnormality in response to ACE inhibition or angiotensin II antagonism. Kidney Int 45(2):485–492

    Article  PubMed  CAS  Google Scholar 

  • Garner MG, Phippard AF, Fletcher PJ, Maclean JM, Duggin GG, Horvath JS, Tiller DJ (1987) Effect of angiotensin II on baroreceptor reflex control of heart rate in conscious baboons. Hypertension 10(6):628–634

    Article  PubMed  CAS  Google Scholar 

  • Guo GB, Abboud FM (1984) Angiotensin II attenuates baroreflex control of heart rate and sympathetic activity. Am J Physiol Heart Circ Physiol 246(1):H80–H89

    Article  CAS  Google Scholar 

  • Harrison-Bernard LM (2009) The renal renin–angiotensin system. Adv Physiol Educ 33(4):270–274

    Article  PubMed  Google Scholar 

  • Hatton R, Clough D, Faulkner K, Conway J (1981) Angiotensin-converting enzyme inhibitor resets baroreceptor reflexes in conscious dogs. Hypertension 3(6):676–681

    Article  PubMed  CAS  Google Scholar 

  • JÓ§hren O, Dendorfer A, Dominiak P (2004) Cardiovascular and renal function of angiotensin II type-2 receptors. Cardiovasc Res 62(3):460–467

    Article  CAS  Google Scholar 

  • Lee WB, Lumbers ER (1981) Angiotensin and the cardiac baroreflex response to phenylephrine. Clin Exp Pharmacol P 8(2):109–117

    Article  CAS  Google Scholar 

  • Lumbers ER, Kingsford NM, Menzies RI, Stevens AD (1992) Acute effects of captopril, an angiotensin-converting enzyme inhibitor, on the pregnant ewe and fetus. Am J Physiol Reg Int Comp Physiol 262(5):R754–R760

    Article  Google Scholar 

  • Martinovic J, Benachi A, Laurent N, Daïkha-Dahmane F, Gubler MC (2001) Fetal toxic effects and angiotensin-II-receptor antagonists. Lancet 358(9277):241–242

    Article  PubMed  CAS  Google Scholar 

  • Matsumura Y, Hasser EM, Bishop VS (1989) Central effect of angiotensin II on baroreflex regulation in conscious rabbits. Am J Physiol Reg Int Comp Physiol 256(3):R694–R700

    Article  CAS  Google Scholar 

  • Mueller CA, Crossley DA II, Burggren WW (2014) The actions of the renin–angiotensin system on cardiovascular and renal development in embryonic chickens (Gallus gallus domesticus). Comp Biochem Physiol A 178:37–45

    Article  CAS  Google Scholar 

  • Mueller CA, Burggren WW, Crossley DA II (2013) Angiotensin II and baroreflex control of heart rate in embryonic chickens (Gallus gallus domesticus). Am J Physiol Reg Int Comp Physiol 305:R855–R863

    Article  CAS  Google Scholar 

  • Nishimura H, Nakamura Y, Sumner RP, Khosla MC (1982) Vasopressor and depressor actions of angiotensin in the anesthetized fowl. Am J Physiol Heart Circ Physiol 242(3):H314–H324

    Article  CAS  Google Scholar 

  • Reid I (1996) Angiotensin II and baroreflex control of heart rate. Physiology 11(6):270–274

    Article  CAS  Google Scholar 

  • Robillard JE, Nakamura KT (1988) Neurohormonal regulation of renal function during development. Am J Physiol Renal Physiol 254(6):F771–F779

    Article  CAS  Google Scholar 

  • Robillard JE, Weismann DN, Gomez RA, Ayres NA, Lawton WJ, VanOrden DE (1983) Renal and adrenal responses to converting-enzyme inhibition in fetal and newborn life. Am J Physiol Reg Int Comp Physiol 244(2):R249–R256

    Article  CAS  Google Scholar 

  • Segar JL, Merrill DC, Robillard JE (1994) Role of endogenous ANG II on resetting arterial baroreflex during development. Am J Physiol Heart Circ Physiol 266(1):H52–H59

    Article  CAS  Google Scholar 

  • Siegel SR, Fisher DA (1980) Ontogeny of the renin–angiotensin–aldosterone system in the fetal and newborn lamb. Pediatr Res 14(2):99–102

    Article  PubMed  CAS  Google Scholar 

  • Silldorff EP, Stephens GA (1992) Effects of converting enzyme inhibition and α receptor blockade on the angiotension pressor response in the American alligator. Gen Comp Endocrinol 87(1):134–140

    Article  PubMed  CAS  Google Scholar 

  • Tate KB, Eme J, Swart J, Conlon JM, Crossley DA II (2012) Effects of dehydration on cardiovascular development in the embryonic American alligator (Alligator mississipiensis). Comp Biochem Physiol A 162:252–258

    Article  CAS  Google Scholar 

  • Tate KB, Rhen T, Eme J, Kohl ZF, Crossley J, Elsey RM, Crossley DA (2016) Periods of cardiovascular susceptibility to hypoxia in embryonic American alligators (Alligator mississippiensis). Am J Physiol Reg Int Comp Physiol 310(11):R1267–R1278

    Article  Google Scholar 

  • Tufro-McReddie A, Romano LM, Harris JM, Ferder L, Gomez RA (1995) Angiotensin II regulates nephrogenesis and renal vascular development. Am J Physiol Renal Physiol 269(1):F110–F115

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The study was supported by the National Science Foundation (Career award IBN IOS-0845741 to DAC).

Author information

Authors and Affiliations

  1. Department of Biological Sciences, California State University San Marcos, 333 S. Twin Oaks Valley Road, San Marcos, CA, USA

    Casey A. Mueller & John Eme

  2. Department of Biology, Truman State University, Kirksville, MO, USA

    Kevin B. Tate

  3. Developmental Integrative Biology, Department of Biological Sciences, University of North Texas, Denton, TX, USA

    Dane A. Crossley II

Authors
  1. Casey A. Mueller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John Eme
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kevin B. Tate
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dane A. Crossley II
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Casey A. Mueller.

Additional information

Communicated by H. V. Carey.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mueller, C.A., Eme, J., Tate, K.B. et al. Chronic captopril treatment reveals the role of ANG II in cardiovascular function of embryonic American alligators (Alligator mississippiensis). J Comp Physiol B 188, 657–669 (2018). https://doi.org/10.1007/s00360-018-1157-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00360-018-1157-2

Keywords

Search

Navigation