Skip to main content
SpringerLink
Log in

Hypertension, calcium channel and pyridoxine (vitamin B6)

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The moderately pyridoxine (vitamin B6)-deficient male rat was introduced by us as an animal model (B6DHT) for the study of hypertension. Hypertension in this rat is associated with increased sympathetic stimulation. Arterial segments from B6DHT rats maintained a higher resting tone. The influx of 45calcium into intracellular compartment of the vascular smooth muscle of the caudate artery of B6DHT rats was also enhanced. Administration of pyridoxine attenuated the hypertension in B6DHT rats as well as in genetic or dietary-induced moderately hypertensive conditions such as in the Zucker obese rat and sucrose or low calcium-fed rats. However, pyridoxine did not have any effect or the spontaneously hypertensive rat. All classes of calcium channel blockers were effective in lowering the systolic blood pressure of B6DHT rats. The increased in vitro influx of45 calcium into intracellular compartment of artery segments of B6DHT rats as well as the BAY K 8644-induced influx of45 calcium into artery segments from normal rats were blocked by pyridoxal phosphate as well as by dihydropyridine-sensitive calcium channel blockers (DHP). Pyridoxal phosphate (PLP) in vitro enhances the binding of calcium channel antagonists to membrane preparations from vascular tissue. PLP corrects the membrane abnormality in responsive hypertensive conditions and thus, could be an endogenous modulator of DHP - sensitive calcium channels.

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. Zucker LM, Zucker TF: Fatty, a new mutation in the rat. J Hered 62: 275–278, 1967

    Google Scholar 

  2. Bray GA: The Zucker-fatty rat: A review. Fed Proc 36: 148–153, 1977

    PubMed  Google Scholar 

  3. Paradise NF, Pilorti CF, Payne WR and Finkelstein JA: Left ventricular functin of the isolated, genetically obese rat's heart. Am J Physiol 248: H438–H444, 1985

    PubMed  Google Scholar 

  4. Preuss HG, Zein M, Knapka J, MacCarthy P, Yousufi AK, Gleim GW, Glace B, Zukowska-Grojec Z: Blood pressure response to sucrose ingestion in four rat strains. Am J Hypertens 5: 244–250, 1992

    PubMed  Google Scholar 

  5. Zein M, Areas JL, Knapka J, MacCarthy P, Yousufi AK, Di Pette D, Holland B, Goel R, Preuss M: Excess sucrose and glucose ingestion acutely elevate blood pressure in spontaneously hypertensive rats. Am J Hypertens 3: 380–386, 1990

    PubMed  Google Scholar 

  6. Paulose CS, Dakshinamurti K, Packer S and Stephens NL: Sympathetic stimulation and hypertension in the pyridoxine-deficient adult rat. Hypertension 11: 387–391, 1988

    PubMed  Google Scholar 

  7. Dakshinamurti K, Stephens MC: Pyridoxine deficiency in the neonate rat. J Neurochem 16: 1515–1522, 1969

    PubMed  Google Scholar 

  8. Bunang RD, Butterfield J: Tail cuff blood pressure measurements without external preheating in the awake rat. Hypertension 4: 898–903, 1982

    PubMed  Google Scholar 

  9. Dakshinamurti K, Paulose, CS, Viswanathan M, Siow YL, Sharma SK, Bolster B: Neurobiology of pyridoxine. Ann NY Acad Sci 585: 129–144, 1990

    Google Scholar 

  10. Paulose CS, Dakshinamurti K J: Chronic catheterization using vascular-access-port in rats: Blood sampling with minimal stress for plasma catecholamine determination. J Neurosci Methods 22: 141–146, 1987

    PubMed  Google Scholar 

  11. Viswanathan M, Paulose KJ, Lal SK, Dakshinamurti, K: Alterations in brain stem α2 adrenoreceptor activity in pyridoxine-deficient rat model of hypertension. Neurosci Lett 111: 201–205, 1990

    PubMed  Google Scholar 

  12. Dalton DW: The cardiovascular effects of centrally administered 5-hydroxytryptamine in the conscious normotensive and hypertensive rat. J Auton Pharmacol 6: 67–75, 1986

    PubMed  Google Scholar 

  13. Wolf WA, Kuhn DM, Lovenberg W: Serotonin and central regulation of arterial blood pressure. In: P.M. Vanhoute (ed.). Serotonin and the Cardiovascular System, Raven Press, New York, NY, pp 63–73, 1985

    Google Scholar 

  14. Peroutka SJ: Receptor 'families' for 5-hydroxytryptamine. J Cardiovasc Pharmacol 16: S8–S14, 1990

    Google Scholar 

  15. Bonate PL: Serotonin receptor subtypes: functional, physiological and clinical correlates. Clin Neuropharmacol 14: 1–16, 1991

    PubMed  Google Scholar 

  16. Cohen ML, Mason N, Wiley KS, Fuller RW: Further evidence that vascular serotonin receptors are of the 5HT2 type. Biochem Pharmacol 32: 567–570, 1983 ai]17._Van Nueten JM, Leyson JE, Schuurkes JAJ, Vanhoute PM: Keanserin: a selective antagonist of 5HT2 serotonergic receptors. Lancet 1: 297–298, 1983 ai]18._Van Neuten JM, Leyson JE, de Clark F, Vanoute PM: Serotonergic receptor subtypes and vascular reactivity. J Cardiovasc Pharmaacol 6: S564–S574, 1984 ai]19._Schalekamp MADH: Serotonergic blockade and hyptertension. In: P.M. Vanhoute (ed.). Serotonin and the Cardiovascular System, Raven Press, New York, NY, pp 135–145, 1985 ai]20._Arvidsson LE, Hacksell V, Nilsson JLG, Hjorth S, Carlsson A, Lindberg P, Sanchez D, Wikstrom H: 8-hydroxy-2-(di-n-propylamino) tetralin, a new centrally acting 5-hydroxytryptamine receptor agonist. J Med Chem 24: 921–923, 1981 ai]21._Wouters W, Tulp MT, Bevan P: Flexinoxan lowers blood pressure and heart rate in cats via 5HT1A receptors. Eur J Pharmacol 149: 213–223, 1988 ai]22._Schoeffler P, Hoyer D: Centrally acting hypotensive agents with affinity for 5HT1A binding sites inhibit forskolin-stimulated adenylate cyclase activity in calf hippocampus. Br J Pharmacol 95: 975–985, 1988 ai]23._Lal KJ, Dakshinamurti K: Hypotensive action of 5-HT receptor agonists in the vitamin B6 deficient hypertensive rat. Eur J Pharmacol 234: 183–189, 1993 ai]24._Groz G, Hantt G, Kolassa N: Urapidil and some analogues with hypotensive properties show high affinities for 5-hydroxytryptamine (5-HT) binding sites of the 5-HT1A subtype and for α1-adrenoreceptor binding sites. Naunyn-Schmiedberg's Arch Pharmacol 336: 597–601, 1987

    Google Scholar 

  17. Nelson D, Taylor WE: Spiroxatrine: A selective serotonin1A receptor antagonist. Eur J Pharmacol 124: 207–208, 1986

    PubMed  Google Scholar 

  18. Rapaport A, Sturtz F, Guicheney P: Regulation of central α-adrenoreceptor by serotonergic denervation. Brain Res 344: 158–161, 1985

    PubMed  Google Scholar 

  19. Noon JP, Rich PJ, Baldessarini RJ: Calcium leakage as a cause of the high resting tension in vascular smooth muscle from the spontaneously hypertensive rat. Proc Natl Acad Sci (USA) 75: 1605–1607, 1978

    Google Scholar 

  20. Postnov YP, Orlov SN: Ion transport across plasma membrane in primary hypertnsion. Physiol Rev 65: 904–945, 1985

    PubMed  Google Scholar 

  21. Viswanathan M, Bose R, Dakshinamurti K: Increased calcium influx in caudal artery of rats made hypertensive with pyridoxine deficiency. Am J Hypertens 4: 252–255, 1991

    PubMed  Google Scholar 

  22. Rapp JP, Nghiem CX, Oniwochei MO: Aortic calcium uptake and effux in spontaneously hypertensive and inbred Dahl rats. J Hypertens 4: 493–499, 1986

    PubMed  Google Scholar 

  23. Bean BP: Classes of calcium channels in vertebrate cells. Ann Rev Physiol 51: 367–384, 1989

    Google Scholar 

  24. Glossman H, Streissnig J: Calcium channels. Vitamins Hormones 44: 155–328, 1988

    PubMed  Google Scholar 

  25. Catterall WA, Seager MJ, Takahashi M: Molecular properties of dihydropyridine-sensitive calcium channels in skeletal muscle. J Biol Chem 263: 3535–3538, 1988

    PubMed  Google Scholar 

  26. Ngheirn CX, Rapp JP: Responses to calcium of chemically skinned vascular smooth muscle from spontaneously hypertensive rats. Clin Exp Hypertens [A] 4: 849–856, 1983

    Google Scholar 

  27. Lal KJ, Dakshinamurti KJ: Calcium channels in vitamin B6 deficiencyinduced hypertension. Hypertension 11: 1357–1362, 1993

    Google Scholar 

  28. Schram M, Thomas G, Towart G, Francowiak, G: Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature 303: 535–537, 1983

    Google Scholar 

  29. Kokbun S, Reuter H: Dihydropyridine derivatives prolong the open state of calcium channels in cultured cardiac cells. Proc Natl Acad Sci (USA) 81: 4824–4827, 1984

    Google Scholar 

  30. Lal KJ, Dakshinamurti K: Relationship between low calcium induced hypertension and vitamin B6 status. J Hypertension 13: 327–332, 1995

    Google Scholar 

  31. Schleiffer R, Pornot F, Berthelot A, Gairard A: Low calcium diet enhances development of hypertension in the spontaneously hypertensive rat. Clin Exp Hypertens [A] 6: 783–793, 1984

    Google Scholar 

  32. Baksi S N, Abhold R H, Speth RC: Low calcium diet increases blood pressure and alters peripheral but not central angiotensin II binding sites in rats. J Hypertens 7: 423–427, 1989

    PubMed  Google Scholar 

  33. Bolton JB: Mechanisms of action of transmitters and other substances on smooth muscle [review]. Physiol Rev 59: 606–718, 1979

    PubMed  Google Scholar 

  34. Brickman AS, Nyby MD, Von Hungen K, Eggena P, Tuck ML: Calcitropic hormones, platelet calcium and blood pressure in essential hypertension. Hypertension 16: 515–522, 1990

    PubMed  Google Scholar 

  35. Bukoski RD, McCarron DA: Altered aortic reactivity and lowered blood pressure associated with high calcium intake. Am J Physiol 25: H978–H983, 1986

    Google Scholar 

  36. Porsti I: Arterial smooth muscle contractions in spontaneously hypertensive rats on a high calcium diet. J Hypertens 10: 255–263, 1992

    PubMed  Google Scholar 

  37. Dominiczak AF, Bohr DF: Cell membrane abnormalities and the regulation of intracellular calcium concentration in hypertension. Clin Sci Colch 79: 415–423, 1990

    PubMed  Google Scholar 

  38. Dakshninamurti K, Lal KJ: Vitamins and Hypertension. In: A.P. Simopoulas (ed.), World Rev Nutr Diat 69: 40–73, 1992

  39. Arvola P, Ruskoaho H, Porsti, I: Effects of high calcium diet on arterial smooth muscle functions and electrolyte balance in mineralocorticoidsalt hypertensive rats. Br J Pharmacol 106: 948–958, 1993

    Google Scholar 

  40. Lal KJ, Sharma SK, Dakshinamurti K: Regulation of calcium influx into vascular smooth muscle by vitamin B6. Clin and Exp Hypertension 15: 489–500, 1993

    Google Scholar 

  41. Zein M, Areas JL, Preus HG: Long-term effects of excess sucrose ingestion on three strains of rats. Am J Hypertens 3: 560–562, 1990

    PubMed  Google Scholar 

  42. Bunag RD, Tomita T, Sasaki S: Chronic sucrose ingestion induces mild hypertension and tachycardia in rats. Hypertension 13: 896–901, 1983

    Google Scholar 

  43. Fournier RD, Chiueh CC, Kopin U, Knapka JJ, Di Pettte D, Preuss HG: Refined carbohydrate increases blood pressure and catecholamine excretion in SHR and WKY. Am J Physiol 250: E381–E385, 1986

    PubMed  Google Scholar 

  44. Lal KJ, Dakshinamurti K, Thliveris J: The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension. J Hypertension 14: 355–363, 1996

    Google Scholar 

  45. Okamoto K, Aoki K: Development of a strain of spontaneously hypertensive rats. Jpn Circ J 27: 282–293, 1963

    PubMed  Google Scholar 

  46. Zemel MB, Peuler JD, Sowers JR, Simpson L: Hypertension in insulinresistant Zucker obese rats is independent of sympathetic neural support. Am J Physiol 262: E368–E371, 1992

    PubMed  Google Scholar 

  47. Yoshioka S, Nishino H, Shiraki T, Ikeda K, Koike H, Okuno A: Antihypertensive effects of CS-045 treatment in obese Zucker rats. Metabolism 42: 75–80, 1993

    PubMed  Google Scholar 

  48. Litwack G: The glucocorticoid receptor at the protein level. Cancer Res 48: 2636–2640, 1988

    PubMed  Google Scholar 

  49. Compton MM, Cidlowski JA: Vitamin B6 and glucocorticoid action. Endocrine Rev 7: 140–148, 1986

    Google Scholar 

  50. Majumdar PK, Joshi JB, Banerjee MR: Correlation between nuclear glucocorticoid receptor levels and casein gene expression in murine mammary glands in vitro. J Biol Chem 258: 6793–6798, 1983

    PubMed  Google Scholar 

  51. Meisler NT, Thanassi JW: Pyridoxine-derived B6 vitamers and pyridoxal 5'-phosphate-binding protein in cytosolic and nuclear fractions of HTC cells. J Biol Chem 265: 1193–1198, 1990

    PubMed  Google Scholar 

  52. Guidetti A, Forchetti CM, Corda MG, Konkel D, Bennett CD, Cossta E: Isolation characterization and purification to homogeneity of an endogenous polypeptide with agonistic action on benzodiazepine receptors. Proc Natl Acad Sci (USA) 80: 3531–3535, 1983

    Google Scholar 

  53. Schmid A, Renaud J, Luxdunski M: Short term and long term effects of β andrenergic effectors and cyclic AMP on nitrendipine-sensitive voltage-dependent Ca2+ channels of skeletal muscle. J Biol Chem 260: 13041–13046, 1985

    PubMed  Google Scholar 

  54. Ferrante J, Triggle DJ: Drug and disease-induced regulation of voltagedependent calcium channels. Pharmacol Rev 42: 29–44, 1990

    PubMed  Google Scholar 

  55. Lewanczuk RZ, Resnick LM, Ho M-S, Benishin CG, Shan J, Pang PKT: Clinical aspects of parathyroid hypertensive factor. J Hypertens 12 (Suppl.): S11–S16, 1994

    Google Scholar 

  56. Lewanczuk RZ, Resnick LM, Blumemfeld JD, Laiagh JH, Pany PK: A new circulating hypertensive factor in the plasma of essential hypertensive subjects. J Hypertens 8: 105–108, 1990

    PubMed  Google Scholar 

  57. Ebersole BJ, Molinoff PB: Identification of ascorbate as an endogenous substance that inhibits binding of dihydropyridine calcium channel blockers. J Neurochem 58: 1300–1309, 1992

    PubMed  Google Scholar 

  58. Simmons MA? Johnson EC, Becker JB, Todd DG, Reichenbecher VE, McCumbee WD, Wright GL: An endogenous 'hypertensive factor' enhances the voltage-dependent calcium current. FEBS Lett 254: 137–140, 1989

    PubMed  Google Scholar 

  59. Spedding M, Mir AK: Direct activations of Ca2+ channels by pamitoyl carnitine? A putative endogenous ligand. Br J Pharmacol 92: 457–468, 1987

    PubMed  Google Scholar 

  60. Triggle DJ: Calcium, calcium channels and calcium channel antagonists. Can J Physiol Pharmacol 68: 1474–1481, 1989

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada

    Krishnamurti Dakshinamurti

  2. Departments of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Krishnamurti Dakshinamurti & Kovvuri Jawahar Lal

  3. Department of Anatomy, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Pallab K. Ganguly

Authors
  1. Krishnamurti Dakshinamurti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kovvuri Jawahar Lal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pallab K. Ganguly
    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

Dakshinamurti, K., Lal, K.J. & Ganguly, P.K. Hypertension, calcium channel and pyridoxine (vitamin B6). Mol Cell Biochem 188, 137–148 (1998). https://doi.org/10.1023/A:1006832810292

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006832810292

Search

Navigation