Skip to main content
SpringerLink
Log in

Haemodynamic responses to angiotensin II in conscious lambs: role of nitric oxide and prostaglandins

  • Integrative Physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

It was hypothesized that nitric oxide (NO) and prostaglandins (PGs) play a synergistic role in modulating haemodynamic responses to angiotensin II (ANG II) in an age-dependent manner. To this end, experiments were carried out in conscious, chronically instrumented lambs aged ∼1 week (N = 9) and ∼6 weeks (N = 10) to evaluate the haemodynamic responses to ANG II, before and after treatment with the l-arginine analogue, N-nitro-l-arginine methyl ester (l-NAME), as well as the cyclooxygenase inhibitor, indomethacin (INDO). Pressor and renal blood flow responses to ANG II were measured before (control) and after administration of l-NAME (20 mg kg−1), following pretreatment with either vehicle (VEH) (experiment 1) or INDO (1 mg kg−1, experiment 2). The two experiments were carried out at minimum intervals of 48 h. In both age groups, the pressor and renal vasoconstrictor responses to ANG II were augmented by pretreatment with INDO, the effects being similar at 1 and 6 weeks. The haemodynamic responses to ANG II were, however, not altered after l-NAME following pretreatment with either VEH or INDO. These data provide new evidence that soon after birth, endogenously produced PGs, but not endogenously produced NO, balance the vasoconstrictor actions of ANG II. There is, however, no apparent interaction between PGs and NO in modulating the responses to ANG II postnatally.

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

Similar content being viewed by others

References

  1. Bonvalet JP, Pradelles P, Farman N (1987) Segmental synthesis and actions of prostaglandins along the nephron. Am J Physiol Renal Physiol 253:F377–F387

    CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Broughton Pipkin F, Kirkpatrick SML, Lumbers ER, Mott JC (1974) Renin and angiotensin-like levels in foetal, new-born and adult sheep. J Physiol 241:575–588

    PubMed  CAS  Google Scholar 

  4. Broughton Pipkin F, Morrison R, O’Brien PM (1989) Prostacyclin attenuates both the pressor and adrenocortical response to angiotensin II in human pregnancy. Clin Sci (Lond) 76:529–534

    CAS  Google Scholar 

  5. Chappellaz ML, Smith FG (2005) Dose dependent systemic and renal haemodynamic effects of angiotensin II in conscious lambs: role of angiotensin AT1 and AT2 receptors. Exp Physiol 90(6):837–845

    Article  PubMed  CAS  Google Scholar 

  6. Chappellaz ML, Smith FG (2007) Systemic and renal hemodynamic effects of the AT1 receptor antagonist, ZD 7155, and the AT2 receptor antagonist, PD 123319, in conscious lambs. Pflügers Arch—Eur J Physiol 453:477–486

    Article  CAS  Google Scholar 

  7. Chiu AT, Carini DJ, Johnson AL, McCall DE, Price WA, Thoolen MJMC, Wong PC, Taber RI, Timmermans PBMWM (1988) Non-peptide angiotensin II receptor antagonists. II. Pharmacology of S-8308. Eur J Pharmacol 157:13–21

    Article  PubMed  CAS  Google Scholar 

  8. Clayton JS, Clark KL, Johns EJ, Drew GM (1998) Effects of prostaglandins and nitric oxide on the renal effects of angiotensin II in the anaesthetized rat. Br J Pharmacol 124:1467–1474

    Article  PubMed  CAS  Google Scholar 

  9. de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T (2000) International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev 52:415–472

    PubMed  Google Scholar 

  10. de Wildt SN, Smith FG (1997) Effects of the angiotensin converting enzyme (ACE) inhibitor, captopril, on the cardiovascular, endocrine and renal responses to furosemide in conscious lambs. Can J Physiol Pharmacol 75:263–270

    Article  PubMed  Google Scholar 

  11. Dudley DT, Panek RL, Major TC, Lu GH, Bruns RF, Klinkefus BA, Hodges JC, Weishaar RE (1990) Subclasses of angiotensin II binding sites and their functional significance. Mol Pharmacol 38:370–377

    PubMed  CAS  Google Scholar 

  12. Ebenezar KK, Ghane FS, Smith FG (2007) Effects of indomethacin on systemic and renal haemodynamics in conscious lambs. Exp Physiol 92:575–581

    Article  PubMed  CAS  Google Scholar 

  13. Ebenezar KK, Ghane FS, Qi W, Smith FG (2010) Do prostaglandins modulate renal haemodynamic effects of endothelin-1in conscious lambs? Can J Physiol Pharmacol 88:161–167

    Article  PubMed  CAS  Google Scholar 

  14. Ferguson AV, Washburn DL (1998) Angiotensin II: a peptidergic neurotransmitter in central autonomic pathways. Prog Neurobiol 54:169–192

    Article  PubMed  CAS  Google Scholar 

  15. Gerber JG, Branch RA, Nies AS, Gerkens JF, Shand DG, Hollifield J, Oates JA (1978) Prostaglandins and renin release: II. Assessment of renin secretion following infusion of PGI2, E2 and D2 into the renal artery of anesthetized dogs. Prostaglandins 15:81–88

    Article  PubMed  CAS  Google Scholar 

  16. Imig JD (2000) Eicosanoid regulation of the renal vasculature. [Review] [184 refs]. Am J Physiol Renal Physiology 279:F965–F981

    CAS  Google Scholar 

  17. Inscho EW, Carmines PK, Navar LG (1990) Prostaglandin influences on afferent arteriolar responses to vasoconstrictor agonists. Am J Physiol 259:F157–F163

    PubMed  CAS  Google Scholar 

  18. Larsson C, Weber P, Anggard E (1974) Arachidonic acid increases and indomethacin decreases plasma renin activity in the rabbit. Eur J Pharmacol 28:391–394

    Article  PubMed  CAS  Google Scholar 

  19. Lonigro AJ, Terragno NA, Malik KU, McGiff JC (1973) Differential inhibition by prostaglandins of the renal actions of pressor stimuli. Prostaglandins 3:595–606

    Article  PubMed  CAS  Google Scholar 

  20. Monument MJ, Smith FG (2003) Age-dependent effects of captopril on the arterial baroreflex control of heart rate in conscious lambs. Exp Physiol 88:761–768

    Article  PubMed  CAS  Google Scholar 

  21. Nasrallah R, Hebert RL (2005) Prostacyclin signaling in the kidney: implications for health and disease. Am J Physiol Renal Physiol 289:F235–F246

    Article  PubMed  CAS  Google Scholar 

  22. Navar LG, Inscho EW, Majid DSA, Imag JD, Harrison-Bernard LM, Mitchell KD (1996) Paracrine regulation of the renal microcirculation. Physiol Rev 76:425–536

    PubMed  CAS  Google Scholar 

  23. Patel A, Smith FG (2001) Age-dependent renal responses to the bradykinin B2 receptor antagonist, icabitant, in conscious lambs. Am J Physiol Regul Integr Comp Physiol 281:R1311–R1318

    PubMed  CAS  Google Scholar 

  24. Patzak A, Lai EY, Mrowka R, Steege A, Persson PB, Persson AE (2004) AT1 receptors mediate angiotensin II-induced release of nitric oxide in afferent arterioles. Kidney Int 66:1949–1958

    Article  PubMed  CAS  Google Scholar 

  25. Pelayo JC, Eisner GM, Jose PA (1981) The ontogeny of the renin–angiotensin system. Clin Perinatol 8:347–359

    PubMed  CAS  Google Scholar 

  26. Purdy KE, Arendshorst WJ (1999) Calcium dependent synthesis of vasodilator renal microvascular prostanoids. Am J Nephrol 277:F850–F858

    CAS  Google Scholar 

  27. Qi Z, Hao CM, Langenbach RI, Breyer RM, Redha R, Morrow JD, Breyer MD (2002) Opposite effects of cyclooxygenase-1 and -2 activity on the pressor response to angiotensin II. J Clin Invest 110:61–69

    PubMed  CAS  Google Scholar 

  28. Seino M, Abe K, Tsunoda K, Yoshinaga K (1985) Interaction of vasopressin and prostaglandins through calcium ion in the renal circulation. Hypertension 7:53–58

    PubMed  CAS  Google Scholar 

  29. Sener A, Smith FG (1999) Acetylcholine chloride and renal haemodynamics during postnatal maturation in conscious lambs. J Appl Physiol 87:1296–1300

    PubMed  CAS  Google Scholar 

  30. Sener A, Smith FG (1999) Dose dependent effects of nitric oxide synthase inhibition on systemic and renal haemodynamics in conscious lambs. Can J Physiol Pharmacol 77:1–7

    Article  PubMed  CAS  Google Scholar 

  31. Sener A, Smith FG (2001) Nitric oxide modulates the arterial baroreflex control of heart rate in conscious lambs in an age-dependent manner. Am J Physiol Heart Circ Physiol 280:2255–2263

    Google Scholar 

  32. Sener A, Smith FG (2001) Renal hemodynamic effects of L-NAME during postnatal maturation in conscious lambs. Pediatr Nephrol 16:868–873

    Article  PubMed  CAS  Google Scholar 

  33. Sener A, Smith FG (2002) Glomerular and tubular responses to N G-nitro-l-arginine methyl ester are age dependent in conscious lambs. Am J Physiol Regul Integr Comp Physiol 282:R1512–R1520

    PubMed  CAS  Google Scholar 

  34. Siragy HM (2000) AT1 and AT2 receptors in the kidney: role in disease and treatment. Am J Kidney Dis 36:S4–S9

    Article  PubMed  CAS  Google Scholar 

  35. Siragy HM, Carey RM (2001) Angiotensin type 2 receptors: potential importance in the regulation of blood pressure. Curr Opin Nephrol Hypertens 10:99–103

    Article  PubMed  CAS  Google Scholar 

  36. Smith RD, Chiu AT, Wong PC, Herblin WF, Timmermans PBMWM (1992) Pharmacology of nonpeptide angiotensin II receptor antagonists. Annu Rev Pharmacol Toxicol 32:135–165

    Article  PubMed  CAS  Google Scholar 

  37. Smith FG, Nohara N, Patel A, Sener A (2002) Endothelin-1 (ET-1) produces no renal vasoconstriction in conscious newborn lambs. Pediatr Nephrol 17:889–895

    Article  PubMed  Google Scholar 

  38. Smith FG, van der Velde L, Sener A (2005) Nitric oxide modulates renal vasoconstrictor effect of endothelin-1 in conscious lambs. Pediatr Nephrol 20:1545–1551

    Article  PubMed  Google Scholar 

  39. Smith FG, Fewell JE, Qi W (2011) Indomethacin abolishes core temperature, but not cardiovascular or renal, responses to lipopolysaccharide in conscious lambs. Clin Exp Pharmacol Physiol 38:494–500

    Article  PubMed  CAS  Google Scholar 

  40. Speth RC, Kim KH (1990) Discrimination of two angiotensin II receptor subtypes with a selective agonist analogue of angiotensin II, p-aminophenylalanine angiotensin II. Biochem Biophys Res Commun 169:997–1006

    Article  PubMed  CAS  Google Scholar 

  41. Thorup C, Kornfeld M, Winaver JM, Goligorsky MS, Moore LC (1998) Angiotensin-II stimulates nitric oxide release in isolated perfused renal resistance arteries. Pflügers Arch 435:432–434

    Article  PubMed  CAS  Google Scholar 

  42. Thorup C, Kornfeld M, Goligorsky MS, Moore LC (1999) AT1 receptor inhibition blunts angiotensin II-stimulated nitric oxide release in renal arteries. J Am Soc Nephrol 10(Suppl 11):S220–S224

    PubMed  CAS  Google Scholar 

  43. Trimper CE, Lumbers ER (1972) The renin angiotensin system in foetal lambs. Pflügers Arch 336:1–10

    Article  PubMed  CAS  Google Scholar 

  44. Villa E, Garcia-Robles R, Haas J, Romero JC (1997) Comparative effect of PGE2 and PGI2 on renal function. Hypertension 30:664–666

    PubMed  CAS  Google Scholar 

  45. Vinagre E, Rodriguez C, San Andres MI, Boggio JC, San Andres MD, Encinas T (1998) Pharmacokinetics of indomethacin in sheep after intravenous and intramuscular administration. J Vet Pharmacol Therap 21:309–314

    Article  CAS  Google Scholar 

  46. Wehlage SJ, Smith FG (2011) Nitric oxide and angiotensin II regulate cardiovascular homeostasis and the arterial baroreflex control of heart rate in conscious lambs. Renin Angiotensin Aldosterone Syst. doi:10.1177/1470320311423282

Download references

Acknowledgements

An operating grant provided by the Canadian Institutes for Health Research supported this work. The authors gratefully acknowledge the expertise of Dr. Wei Qi in surgically instrumenting the experimental animals and carefully critiquing of the manuscript and Ms. Lucy Yu for technical assistance. Dr. Kesavarao K. Ebenezar was supported by a post-doctoral fellowship provided by the Canadian Institutes for Health Research Training Program in Genetics, Child Development, and Health.

Author information

Authors and Affiliations

  1. Department of Physiology & Pharmacology, Alberta Children’s Hospital Research Institute for Child and Maternal Health, Faculty of Medicine, University of Calgary, 3330 Hospital Drive, NW, Calgary, AB, T2N 4N1, Canada

    Kesavarao Kumar Ebenezar, Andy Kin On Wong & Francine Gabriel Smith

Authors
  1. Kesavarao Kumar Ebenezar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andy Kin On Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francine Gabriel Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francine Gabriel Smith.

Additional information

Portion of this manuscript was presented as a poster to Experimental Biology 2008 and published in the proceedings (Ebenezar KK, Wong AKO, Smith FG (2008) Pressor and renal haemodynamic responses to angiotensin II in conscious lambs: role of nitric oxide and prostaglandins. FASEB J 22:735.8).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ebenezar, K.K., Wong, A.K.O. & Smith, F.G. Haemodynamic responses to angiotensin II in conscious lambs: role of nitric oxide and prostaglandins. Pflugers Arch - Eur J Physiol 463, 399–404 (2012). https://doi.org/10.1007/s00424-011-1065-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-011-1065-8

Keywords

Search

Navigation