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Berg T, Walaas SI, Roberg BÅ, et al. Plasma Norepinephrine in Hypertensive Rats Reflects α(2)-Adrenoceptor Release Control Only When Re-Uptake is Inhibited. Front Neurol. 2012;3:160doi: 10.3389/fneur.2012.00160.
Berg, T., Walaas, S. I., Roberg, B. �. �., Huynh, T. T., & Jensen, J. (2012). Plasma Norepinephrine in Hypertensive Rats Reflects α(2)-Adrenoceptor Release Control Only When Re-Uptake is Inhibited. Frontiers in neurology, 3160. https://doi.org/10.3389/fneur.2012.00160
Berg, Torill, et al. "Plasma Norepinephrine in Hypertensive Rats Reflects α(2)-Adrenoceptor Release Control Only When Re-Uptake is Inhibited." Frontiers in neurology vol. 3 (2012): 160. doi: https://doi.org/10.3389/fneur.2012.00160
Berg T, Walaas SI, Roberg BÅ, Huynh TT, Jensen J. Plasma Norepinephrine in Hypertensive Rats Reflects α(2)-Adrenoceptor Release Control Only When Re-Uptake is Inhibited. Front Neurol. 2012 Nov 08;3:160. doi: 10.3389/fneur.2012.00160. eCollection 2012. PMID: 23162530; PMCID: PMC3492874.
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Front Neurol. 2012 Nov 08;3:160. doi: 10.3389/fneur.2012.00160. eCollection 2012.

Plasma Norepinephrine in Hypertensive Rats Reflects α(2)-Adrenoceptor Release Control Only When Re-Uptake is Inhibited.

Frontiers in neurology

Torill Berg, Sven Ivar Walaas, Bjørg Åse Roberg, Trang Thi Huynh, Jørgen Jensen

Affiliations

  1. Department of Physiology, Institute of Basic Medical Sciences, University of Oslo Oslo, Norway.

PMID: 23162530 PMCID: PMC3492874 DOI: 10.3389/fneur.2012.00160

Abstract

UNLABELLED: α(2)-adrenoceptors (AR) lower central sympathetic output and peripheral catecholamine release, thereby protecting against sympathetic hyperactivity and hypertension. Norepinephrine re-uptake-transporter effectively (NET) removes norepinephrine from the synapse. Overflow to plasma will therefore not reflect release. Here we tested if inhibition of re-uptake allowed presynaptic α(2)AR release control to be reflected as differences in norepinephrine overflow in anesthetized hypertensive spontaneously hypertensive rats (SHR) and normotensive rats (WKY). We also tested if α(2)AR modulated the experiment-induced epinephrine secretion, and a phenylephrine-induced, α(1)-adrenergic vasoconstriction. Blood pressure was recorded through a femoral artery catheter, and cardiac output by ascending aorta flow. After pre-treatment with NET inhibitor (desipramine), and/or α(2)AR antagonist (yohimbine, L-659,066) or agonist (clonidine, ST-91), we injected phenylephrine. Arterial blood was sampled 15 min later. Plasma catecholamine concentrations were not influenced by phenylephrine, and therefore reflected effects of pre-treatment. Desipramine and α(2)AR antagonist separately had little effect on norepinephrine overflow. Combined, they increased norepinephrine overflow, particularly in SHR. Clonidine, but not ST-91, reduced, and pertussis toxin increased norepinephrine overflow in SHR and epinephrine secretion in both strains. L-659,066 + clonidine (central α(2)AR-stimulation) normalized the high blood pressure, heart rate, and vascular tension in SHR. α(2)AR antagonists reduced phenylephrine-induced vasoconstriction equally in WKY and SHR.

CONCLUSIONS: α(2A)AR inhibition increased norepinephrine overflow only when re-uptake was blocked, and then with particular efficacy in SHR, possibly due to their high sympathetic tone. α(2A)AR inhibited epinephrine secretion, particularly in SHR. α(2A)AR supported α(1)AR-induced vasoconstriction equally in the two strains. α(2)AR malfunctions were therefore not detected in SHR under this basal condition.

Keywords: catecholamine release; epinephrine; hypertension; norepinephrine; norepinephrine re-uptake transporter; plasma catecholamine concentrations; sympathetic nervous system activity; α2-adrenoceptors

References

  1. Naunyn Schmiedebergs Arch Pharmacol. 2007 Oct;376(1-2):45-63 - PubMed
  2. J Pharmacol Exp Ther. 1988 Apr;245(1):32-40 - PubMed
  3. Neuropharmacology. 2002 Dec;43(8):1249-57 - PubMed
  4. Biol Pharm Bull. 2011;34(9):1373-6 - PubMed
  5. J Hypertens. 2003 Jul;21(7):1363-9 - PubMed
  6. Expert Opin Ther Pat. 2011 Apr;21(4):455-81 - PubMed
  7. Mol Endocrinol. 2003 Aug;17(8):1640-6 - PubMed
  8. J Am Acad Child Adolesc Psychiatry. 1995 Jan;34(1):50-4 - PubMed
  9. Nature. 1999 Nov 11;402(6758):181-4 - PubMed
  10. J Vasc Res. 2009;46(1):25-35 - PubMed
  11. Br J Pharmacol. 1998 Mar;123(6):1205-13 - PubMed
  12. Eur J Pharmacol. 2003 Apr 18;466(3):301-10 - PubMed
  13. Eur J Pharmacol. 2002 Oct 11;452(3):325-37 - PubMed
  14. Eur J Pharmacol. 1992 Feb 11;211(2):257-61 - PubMed
  15. Eur J Pharmacol. 1992 Sep 4;219(3):465-8 - PubMed
  16. Curr Top Med Chem. 2007;7(2):187-94 - PubMed
  17. Acta Physiol Scand. 2005 Jun;184(2):121-30 - PubMed
  18. J Pharmacol Exp Ther. 2005 Aug;314(2):804-10 - PubMed
  19. J Neurochem. 2001 Aug;78(4):685-93 - PubMed
  20. Hypertension. 1999 Jan;33(1):14-7 - PubMed
  21. Am J Physiol Regul Integr Comp Physiol. 2002 Aug;283(2):R287-95 - PubMed
  22. Nat Med. 2007 Mar;13(3):315-23 - PubMed
  23. Hypertension. 2002 Sep;40(3):342-7 - PubMed
  24. Br J Pharmacol. 1998 Nov;125(6):1144-9 - PubMed
  25. Hypertension. 2010 May;55(5):1224-30 - PubMed
  26. J Cardiovasc Pharmacol. 1989 Mar;13(3):440-6 - PubMed
  27. Br J Pharmacol. 1994 Dec;113(4):1567-73 - PubMed
  28. Basic Clin Pharmacol Toxicol. 2011 Jun;108(6):365-70 - PubMed
  29. Circ Res. 1976 Jun;38(6 Suppl 2):21-9 - PubMed
  30. Br J Pharmacol. 2006 Dec;149(8):1049-58 - PubMed
  31. Hypertension. 1999 Sep;34(3):403-7 - PubMed
  32. Science. 1996 Aug 9;273(5276):801-3 - PubMed
  33. Am J Physiol. 1991 Apr;260(4 Pt 2):R824-32 - PubMed
  34. Front Neurol. 2011 Nov 23;2:71 - PubMed

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