Skip to main content
SpringerLink
Log in

Effects of pheochromocytoma on cardiovascular alpha adrenergic receptor system

  • Originals
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Summary

We have examined the in vivo consequences of prolonged stimulation of the cardiovascular alpha-adrenergic receptor system in a rat model harboring pheochromocytoma. New England Deaconess Hospital rats with transplanted pheochromocytomas developed systolic hypertension and their plasma norepinephrine concentrations were approximately 60-fold greater than controls. Alpha1-adrenergic receptors were quantitated in hearts from controls and rats with transplanted pheochromocytoma using the alpha1-receptor selective antagonist [3H]prazosin. Down-regulation of alpha1-receptors was found in the hearts of pheochromocytoma rats(33.0 vs. 23.0 fmol/mg protein) without any significant change in the affinities of these receptors for the circulating catecholamine, norepinephrine. Furthermore, the responsiveness of the blood vessel to the alpha-adrenergic stimulation was assessed using in vitro contratile experiments. Aortic rings from pheochromocytoma animals showed an eight fold decrease in sensitivity (EC50) and a 74% decrease in maximal contracility (Emax) to norepinephrine as compared with controls. Similarly, mesenteric artery rings prepared from the same animals showed a five fold loss of EC50 but no decrease in Emax to phenylephrine as compared with controls. In addition, serotonin EC50 and Emax of these mesentery preparations remained unaltered. Coupled with our previous findings [9], the present study suggests that rats with pheochromocytoma secreting large amounts of norepinephrine provide a valuable model system for studying in vivo desensitization of the cardiovascular alpha-receptor systems as well as the beta-adrenergic receptor system.

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

Similar content being viewed by others

References

  1. Hoffman BB, Lefkowitz RJ (1980) Radioligand binding studies of adrenergic receptors: new insight into molecular and physiological regulation. Annu Rev Pharmacol Toxicol 20: 581–608

    PubMed  Google Scholar 

  2. Harden TK (1983) Agonist-induced desensitization of the β-adrenergic receptor-linked adenylate cyclase. Pharmacol Rev 35: 5–32

    PubMed  Google Scholar 

  3. Stiles GL, Caron MG, Lefkowitz RJ (1984) β-adrenergic receptors: biochemical mechanisms of physiological regulation. Physiol Rev 64: 661–743

    PubMed  Google Scholar 

  4. Stiles GL, Lefkowitz RJ (1984) Cardiac adrenergic receptors. Annu Rev Med 35: 149–164

    PubMed  Google Scholar 

  5. Tsujimoto G, Hoffman BB (1985) Desensitization of β-adrenergic receptor-mediated vascular smooth muscle relaxation. Mol Pharmacol 27: 210–217

    PubMed  Google Scholar 

  6. Carrier O, Wedell EK, Barron KW (1978) Specific α-adrenergic receptor desensitization in vascular smooth muscle. Blood Vessels 15: 247–258

    PubMed  Google Scholar 

  7. Lurie KG, Tsujimoto G, Hoffman BB (1985) Desensitization of α-adrenergic receptor-mediated vascular smooth muscle contraction. J Pharmacol Exp Ther 234: 147–152

    PubMed  Google Scholar 

  8. Warren S, Chute RN (1972) Pheochromocytoma. Cancer 29: 327–331

    PubMed  Google Scholar 

  9. Tsujimoto G, Manger WM, Hoffman BB (1984) Desensitization of β-adrenergic receptors by pheochromocytoma. Endocrinology 114: 1272–1278

    PubMed  Google Scholar 

  10. Kuchel O (1977) Autonomic nervous system in hypertension: Clinical aspects. In: Genest J, Koiw E, Kuchel O (eds) Hypertension. McGraw-Hill, New York, p 101

    Google Scholar 

  11. Bravo EL, Tarazi RS, Gifford RW, Steward BH (1979) Circulating and urinary catecholamines in pheochromocytoma. N Engl J Med 301: 682–686

    PubMed  Google Scholar 

  12. Manger WM, Hulse MC, Forsyth ML, Chute RN, Brown CE, Webb K, Sussman R, Warren S (1982) Effect of pheochromocytoma and hypophysectomy on blood pressure and catecholamines in NEDH rats. Hypertension 4(Suppl II): 200–207

    PubMed  Google Scholar 

  13. Mefford IN, Ward NM, Miles L, Taylor B, Chesney M, Keegan DL, Barchus JD (1981) Determination of plasma catecholamines and free 3, 4 dihydroxyphenyl acetic acid in continuously collected human plasma by high performance liquid chromatography with electrochemical detection. Life Sci 28: 477–483

    PubMed  Google Scholar 

  14. Minneman KP, Hegestrand LR, Molinoff PB (1979) Simultaneous determination of beta1- and beta2-adrenergic receptors in tissue containing both receptor subtypes. Mol Pharmacol 16: 34–46

    PubMed  Google Scholar 

  15. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193: 265–275

    PubMed  Google Scholar 

  16. Peck CC, Barrett BB (1979) Nonlinear least-squares regression programs for microcomputers. J Pharmacokinet Biopharm 7: 537–541

    PubMed  Google Scholar 

  17. Cheng Y, Prusoff WH (1973) Relationship between the inhibition constant (KI) and the concentration inhibitor which causes 50% inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22: 3099–3108

    PubMed  Google Scholar 

  18. DeLean A, Munson PJ, Rodbard D (1978) Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol 235: E97-E102

    PubMed  Google Scholar 

  19. Chalfie M, Perlman RL (1976) Studies of transplantable rat pheochromocytoma: Biochemical characterization and catecholamine secretion. J Pharmacol Exp Ther 197: 615–622

    PubMed  Google Scholar 

  20. Snavely MD, Mahan LC, O'Connor DT, Insel PA (1983) Selective down regulation of adrenergic receptor subtypes in tissues from rats with pheochromocytoma. Endocrinology 113: 354–361

    PubMed  Google Scholar 

  21. Colucci WS, Gimbrone MA Jr, Alexander RW (1980) Characterization of post-synaptic alpha-adrenergic receptors by [3H]-dihydroergocryptine binding in muscular arteries from the rat mesentery. Hypertension 2: 149–155

    PubMed  Google Scholar 

  22. Colucci WS, Gimbrone MA Jr, Alexander RW (1981) Regulation of the post-synaptic alpha-adrenergic receptor in rat mesenteric artery: Effect of chemical sympathectomy and epinephrine treatment. Circ Res 48: 104–111

    PubMed  Google Scholar 

  23. Ruffolo RR Jr, Waddell JE, Yaden EM (1982) Heterogeneity of postsynaptic alpha adrenergic receptors in mammalian aortas. J Pharmacol Exp Ther 221: 309–314

    PubMed  Google Scholar 

  24. Su Y-F, Harden TK, Perkins JP (1980) Catecholamine-specific desensitization of adenylate cyclase: Evidence for a multiple process. J Biol Chem 255: 7410–7419

    PubMed  Google Scholar 

  25. Snavely MD, Moustafa E, Motulsky HJ, Mahan LC, Insel PA (1982) Beta-adrenergic receptor subtypes in the rat renal cortex: selective regulation of beta1-adrenergic receptors by phenochromocytoma. Circ Res 51: 504–513

    PubMed  Google Scholar 

  26. Benfey BG, Varma DR (1967) Interactions of sympathomimetic drugs, propranolol and phentolamine on atrial refractory period and contractility. Br J Pharmacol 30: 603–611

    PubMed  Google Scholar 

  27. Govier WC (1968) Myocardial alpha adrenergic receptors and their role in the production of a positive inotropic effect by sympathomimetic agents. J Pharmacol Exp Ther 159: 82–90

    PubMed  Google Scholar 

  28. Schümann HJ, Endoh M, Wagner J (1974) Positive inotropic effects of phenylephrine in the isolated rabbit pulmonary muscle mediated both by α-and β-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol 284: 133–148

    PubMed  Google Scholar 

  29. Wagner J, Endoh M, Reinhardt D (1974) Stimulation by phenylephrine of adrenergic alpha and beta-receptors in the isolated perfused rabbit heart. Naunyn Schmiedebergs Arch Pharmacol 282: 307–310

    PubMed  Google Scholar 

  30. Benfey BG (1982) Function of myocardial α-adrenoceptors. Life Sci 31: 101–112

    PubMed  Google Scholar 

  31. Endoh M (1982) Adrenoceptors and the myocardial inotropic response: Do alpha and beta receptor sites functionally coexist? In: Kalsner S (ed) Trends in autonomic pharmacology. Urban & Schwarzenberg, Baltimore-Munich, pp 303–322

    Google Scholar 

  32. Williams RS, Dukes DF, Lefkowitz RJ (1981) Subtype specificity of α-adrenergic receptors in rat heart. J Cardiovasc Pharmacol 3: 522–531

    PubMed  Google Scholar 

  33. Winquist RJ, Webb RC, Bohr DF (1982) Vascular smooth muscle in hypertension. Fed Proc 41: 2387–2393

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Department of Pharmacology, Yamanashi Medical College, 1110 Tamaho-cho, Nakakoma-gun, 409-38, Yamanashi, Japan

    Gozoh Tsujimoto & Keitaro Hashimoto

  2. The Department of Medicine, Stanford University School of Medicine, Stanford, California, USA

    Brian B. Hoffman

Authors
  1. Gozoh Tsujimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keitaro Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian B. Hoffman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsujimoto, G., Hashimoto, K. & Hoffman, B.B. Effects of pheochromocytoma on cardiovascular alpha adrenergic receptor system. Heart Vessels 1, 152–157 (1985). https://doi.org/10.1007/BF02066410

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02066410

Key words

Search

Navigation