Skip to main content
Log in

Antihypertensive Activity of Secoisolariciresinol Diglucoside (SDG) Isolated from Flaxseed: Role of Guanylate Cyclase

  • Original Articles
  • Published:
International Journal of Angiology

Abstract

Secoisolariciresinol diglucoside (SDG), a lignan isolated from flaxseed, is a phytoestrogen. Estrogens and phytoestrogen from soy have been reported to have mild hypotensive effects. Effects of SDG on arterial pressures are not known. The objective of this study was to determine whether (a) SDG has a hypotensive effect, and (b) the hypotensive effect is mediated through the L-arginine-nitric oxide pathway. The studies were conducted in anesthetized Sprague Dawley normotensive rats weighing between 450 and 500 grams Carotid arterial pressures were recorded to investigate the changes in the arterial pressures and heart rate with various doses of SDG. Maximum drops in the mean arterial pressure, which occurred at 15 minutes after intravenous SDG, were 40%, 41%, and 47%, respectively, with 10 mg, 15 mg, and 20 mg/kg of SDG. The pressures tended to recover, but even at the end of four hours, the percent drops in the mean arterial pressures were 33, 22, and 29, respectively, with 10 mg, 15 mg, and 20 mg/kg of SDG. The drops in the diastolic and mean arterial pressures were slightly higher than systolic pressures. Smaller doses of SDG (3 and 5 mg/kg) produced dose-dependent decreases in the systolic, diastolic, and mean arterial pressures. Heart rate remained unchanged. Pretreatment with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase, did not prevent the SDG-induced reduction in arterial pressures. However, pretreatment with methylene blue (MB), a nonspecific, and oxadiazolo quinoxalin (ODQ), a specific inhibitor of guanylate cyclase, completely prevented the SDG-induced reduction in the arterial pressures. These results suggest that SDG is a long-acting hypotensive agent, and that the hypotensive effect is mediated through the guanylate cyclase enzyme.

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

Access this article

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

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

References

  1. NS Hettiarachchy GA Hareland A Ostenson G Bladner-Shank (1990) ArticleTitleChemical composition of 11 flaxseed varieties grown in North Dakota Proc Flax Inst 53 36

    Google Scholar 

  2. BD Oomah G Mazza (1993) ArticleTitleFlaxseed proteins: A review Food Chem 48 109–114 Occurrence Handle10.1016/0308-8146(93)90043-F Occurrence Handle1:CAS:528:DyaK3sXmt1Cnu7s%3D

    Article  CAS  Google Scholar 

  3. DS Kelley LB Branch JE Love PC Taylor YM Rivera JM Iacono (1991) ArticleTitleDietary alpha-linolenic acid and immunocompetence in humans Am J Clin Nutr 53 40–46 Occurrence Handle1:CAS:528:DyaK3MXhvVCiu7c%3D Occurrence Handle1670594

    CAS  PubMed  Google Scholar 

  4. JE Hunter (1990) ArticleTitleN-3 fatty acids from vegetable oils Am J Clin Nutr 51 809–814 Occurrence Handle1:CAS:528:DyaK3cXltFCjsL8%3D Occurrence Handle1970702

    CAS  PubMed  Google Scholar 

  5. K Prasad SV Mantha AD Muir ND Westcott (1998) ArticleTitleReduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid Atherosclerosis 136 367–375 Occurrence Handle10.1016/S0021-9150(97)00239-6 Occurrence Handle1:CAS:528:DyaK1cXhs1CqsL4%3D Occurrence Handle9543108

    Article  CAS  PubMed  Google Scholar 

  6. Westcott ND, Muir AD (1998) Process for extracting lignans from flaxseed. US Patent No. 5705618

  7. K Prasad (1999) ArticleTitleReduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside (SDG) isolated from flaxseed Circulation 99 1355–1362 Occurrence Handle1:CAS:528:DyaK1MXitVyms78%3D Occurrence Handle10077521

    CAS  PubMed  Google Scholar 

  8. JS Gavaler ER Rosenblum SR Deal BT Bowie (1995) ArticleTitleThe phytoestrogen congeners of alcoholic beverages: Current status Proc Soc Exp Biol Med 208 98–102 Occurrence Handle1:CAS:528:DyaK2MXivFehtLk%3D Occurrence Handle7892304

    CAS  PubMed  Google Scholar 

  9. WR Obermeyer SM Musser JM Betz RE Casey AE Pohland SW Page (1995) ArticleTitleChemical studies of phytoestrogens and related compounds in dietary supplements: Flax and chaparral Proc Soc Exp Biol Med 208 6–12 Occurrence Handle1:CAS:528:DyaK2MXivFeht7w%3D Occurrence Handle7892296

    CAS  PubMed  Google Scholar 

  10. HJ Teede FS Dalais D Kotsopoulos YL Liang S Davis BP McGrath (2001) ArticleTitleDietary soy has both beneficial and potentially adverse cardiovascular effects: A placebo-controlled study in men and postmenopausal women J Clin Endocrinol Metab 86 3053–3060 Occurrence Handle10.1210/jc.86.7.3053 Occurrence Handle1:CAS:528:DC%2BD3MXlt1Gjsbo%3D Occurrence Handle11443167

    Article  CAS  PubMed  Google Scholar 

  11. S Washburn GL Burke T Morgan M Anthony (1999) ArticleTitleEffect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women Menopause 6 7–13 Occurrence Handle1:STN:280:DyaK1M7pvF2ntQ%3D%3D Occurrence Handle10100174

    CAS  PubMed  Google Scholar 

  12. RP Garay M Alvarez-Guerra JO Alda C Nazaret A Soler F Vargas (1998) ArticleTitleRegulation of renal Na-K-Cl cotransporter NKCC2 by humoral natriuretic factors: Relevance in hypertension Clin Exp Hypertens 20 675–682 Occurrence Handle1:CAS:528:DyaK1cXkvVWjsLs%3D Occurrence Handle9682923

    CAS  PubMed  Google Scholar 

  13. LA Simons M Konigsmark ParticleVon J Simons DS Celermajer (2000) ArticleTitlePhytoestrogens do not influence lipoprotein levels or endothelial function in healthy postmenopausal women Am J Cardiol 85 1297–1301 Occurrence Handle10.1016/S0002-9149(00)00759-1 Occurrence Handle1:CAS:528:DC%2BD3cXjs1Cgs7o%3D Occurrence Handle10831943

    Article  CAS  PubMed  Google Scholar 

  14. GM Rosano PM Sarrel PA Poole-Wilson P Collins (1993) ArticleTitleBeneficial effect of oestrogen on exercise-induced myocardial ischemia in women with coronary artery disease Lancet 342 133–136 Occurrence Handle10.1016/0140-6736(93)91343-K Occurrence Handle1:STN:280:ByyA38zmt1Q%3D Occurrence Handle8101254

    Article  CAS  PubMed  Google Scholar 

  15. DM Gilligan DM Badar JA Panza AA Quyyumi RO Cannon SuffixIII (1994) ArticleTitleAcute vascular effects of estrogen in postmenopausal women Circulation 90 786–791 Occurrence Handle1:STN:280:ByuA38%2FisFA%3D Occurrence Handle8044949

    CAS  PubMed  Google Scholar 

  16. V Guetta AA Quyyumi A Prasad JA Panza M Waclawiw RO Cannon SuffixIII (1997) ArticleTitleThe role of nitric oxide in coronary vascular effects of estrogen in postmenopausal women Circulation 96 2795–2801 Occurrence Handle1:CAS:528:DyaK2sXnvFajsLs%3D Occurrence Handle9386140

    CAS  PubMed  Google Scholar 

  17. R Raddino C Manca E Poli R Bolognesi O Visioli (1986) ArticleTitleEffects of 17 β-estradiol on isolated rabbit heart Arch Intl Pharmacodyn Ther 281 57–65 Occurrence Handle1:CAS:528:DyaL28Xkslaqsr0%3D

    CAS  Google Scholar 

  18. R Vargas G Thomas B Wroblewska PW Ramwell (1989) ArticleTitleDifferential effects of 17α- and 17β-estradiol on PGF-mediated contraction of the porcine coronary artery Adv Prost Thromb Leukot Res 19 277–280 Occurrence Handle1:CAS:528:DyaL1MXkslWitrk%3D

    CAS  Google Scholar 

  19. E Salas MG Lopez M Villarroya P Sanchez-Garcia R Pascual ParticleDe WR Dixon AG Garcia (1994) ArticleTitleEndothelium-dependent relaxation by 17α-estradiol of pig coronary arteries Eur J Pharmacol 258 47–55 Occurrence Handle10.1016/0014-2999(94)90056-6 Occurrence Handle1:CAS:528:DyaK2cXkt1Oiu74%3D Occurrence Handle7925599

    Article  CAS  PubMed  Google Scholar 

  20. V Gisclard VM Miller PM Vanhoutte (1988) ArticleTitleEffect of estradiol on endothelium-dependent responses in rabbit J Pharmacol Exp Ther 244 19–22 Occurrence Handle1:CAS:528:DyaL1cXovVamtA%3D%3D Occurrence Handle3121846

    CAS  PubMed  Google Scholar 

  21. K Prasad J Kalra AK Chaudhary D Debnath (1990) ArticleTitleEffect of polymorphonuclear leukocyte-derived oxygen free radicals and hypochlorous acid on cardiac function and some biochemical parameters Am Heart J 119 538–550 Occurrence Handle1:CAS:528:DyaK3cXlsV2rtrY%3D Occurrence Handle2155522

    CAS  PubMed  Google Scholar 

  22. R Kapoor K Prasad (1996) ArticleTitleRole of polymorphonuclear leukocytes in cardiovascular depression and cellular injury in hemorrhagic shock and reinfusion Free Radic Biol Med 21 609–618 Occurrence Handle10.1016/0891-5849(96)00156-6 Occurrence Handle1:CAS:528:DyaK28Xmt12lsbg%3D Occurrence Handle8891664

    Article  CAS  PubMed  Google Scholar 

  23. K Prasad JB Gupta J Kalra P Lee SV Mantha B Bharadwaj (1996) ArticleTitleOxidative stress as a mechanism of cardiac failure in chronic volume overload in canine model J Mol Cell Cardiol 28 375–385 Occurrence Handle10.1006/jmcc.1996.0035 Occurrence Handle1:CAS:528:DyaK28Xht1emsLc%3D Occurrence Handle8729069

    Article  CAS  PubMed  Google Scholar 

  24. RM Palmer DS Ashton S Moncada (1988) ArticleTitleVascular endothelial cells sythesize nitric oxide from L-arginine Nature 333 664–666 Occurrence Handle10.1038/333664a0 Occurrence Handle1:CAS:528:DyaL1cXktlGktb8%3D Occurrence Handle3131684

    Article  CAS  PubMed  Google Scholar 

  25. N Baker E Sipkema (1997) ArticleTitleComponents of acetylcholine-induced dilation in isolated rat arterioles Am J Physiol (Heart Circ Physiol) . H1848–H1853

    Google Scholar 

  26. H Dong GJ Waldron D Galipeau WC Cole CR Triggle (1997) ArticleTitleNo/PGI2-independent vasorelaxation and the cytochrome P450 pathway in rabbit carotid artery Br J Pharmacol 120 695–701 Occurrence Handle1:CAS:528:DyaK2sXhsVeiu7k%3D Occurrence Handle9051310

    CAS  PubMed  Google Scholar 

  27. K Thomson I Rubin M Lauritzen (2000) ArticleTitleIn vivo mechanisms of acetylcholine-induced vasodilation in rat sciatic nerve Am J Physiol (Heart Circ Physiol) 279 H1044–H1054

    Google Scholar 

  28. DD Rees RMJ Palmer HF Hodson S Moncada (1989) ArticleTitleA specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation Br J Pharmacol 96 418–424 Occurrence Handle1:CAS:528:DyaL1MXhtFagtrk%3D Occurrence Handle2924084

    CAS  PubMed  Google Scholar 

  29. MD Randall DA Kendall (1997) ArticleTitleInvolvement of a cannabinoid in endothelium-derived hyperpolarizing factor-mediated coronary vasorelaxation Eur J Pharmacol 335 205–209 Occurrence Handle10.1016/S0014-2999(97)01237-5 Occurrence Handle1:CAS:528:DyaK2sXmsVKmtrs%3D Occurrence Handle9369375

    Article  CAS  PubMed  Google Scholar 

  30. PC Wong WA Price SuffixJr AT Chiu JV Duncia DJ Carini RR Wexler AL Johnson P Timmermans (1990) ArticleTitleHyptensive action of DuP 753, an angiotensin II antagonist, in spontaneously hypertensive rats. Nonpeptide angiotensin II receptor antagonists:X Hypertension 15 459–468 Occurrence Handle1:CAS:528:DyaK3cXksFahtL0%3D Occurrence Handle2185150

    CAS  PubMed  Google Scholar 

  31. JB Gupta K Prasad (1992) ArticleTitleMechanism of H2O2-induced modulation of airway smooth muscle Am J Physiol 263 L714–L722 Occurrence Handle1:CAS:528:DyaK3sXpsFygtA%3D%3D Occurrence Handle1335702

    CAS  PubMed  Google Scholar 

  32. MZ Goren A Akici A Karaalp R Aker S Oktay (2001) ArticleTitleThe role of nitric oxide in the reversal of hemorrhagic shock by oxotremorine Eur J Pharmacol 428 261–267 Occurrence Handle10.1016/S0014-2999(01)01294-8 Occurrence Handle1:CAS:528:DC%2BD3MXnslajs7Y%3D Occurrence Handle11675044

    Article  CAS  PubMed  Google Scholar 

  33. TC Hua SM Moochhala (2000) ArticleTitleRole of nitric oxide in hemorrhagic shock-induced bacterial translocation J Surg Res 93 247–256 Occurrence Handle10.1006/jsre.2000.5991 Occurrence Handle1:CAS:528:DC%2BD3cXntFOku7s%3D Occurrence Handle11027467

    Article  CAS  PubMed  Google Scholar 

  34. WGM Martin D Villani D Jothianandan RF Furchgott (1985) ArticleTitleSelective blockade of epithelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta J Pharmacol Exp Ther 232 708–716 Occurrence Handle1:CAS:528:DyaL2MXhvFOktrs%3D Occurrence Handle2983068

    CAS  PubMed  Google Scholar 

  35. NK Jain CS Patil A Singh SK Kulkarni (2001) ArticleTitleSildenafil-induced peripheral analgesia and activation of nitric oxide-cyclic GMP pathway Brain Res 909 170–178 Occurrence Handle10.1016/S0006-8993(01)02673-7 Occurrence Handle1:CAS:528:DC%2BD3MXls1ejsLo%3D Occurrence Handle11478933

    Article  CAS  PubMed  Google Scholar 

  36. H Koelzow JA Gedney J Baumann NJ Snook MC Bellamy (2002) ArticleTitleThe effect of methylene blue on the hemodynamic changes during ischemia reperfusion injury in orthotopic liver transplantation Anesth Analg 94 824–829 Occurrence Handle10.1097/00000539-200204000-00009 Occurrence Handle1:CAS:528:DC%2BD38XjtFCgt7g%3D Occurrence Handle11916779

    Article  CAS  PubMed  Google Scholar 

  37. J Garthwaite E Southam CL Boulton EB Nielsen K Schmidt B Mayer (1995) ArticleTitleInhibition of nitric oxide-sensitive guanylyl cyclase by oxidiazoloquinoxaline derivative, ODQ Mol Pharmacol 48 184–188 Occurrence Handle1:CAS:528:DyaK2MXnvVKhsr0%3D Occurrence Handle7544433

    CAS  PubMed  Google Scholar 

  38. F Brunner K Schmidt EB Nielsen B Mayer (1996) ArticleTitleNovel guanylyl cyclase inhibitor potently inhibits cyclic GMP accumulation in endothelial cells and relaxation of bovine pulmonary artery J Pharmacol Exp Ther 277 48–53 Occurrence Handle1:CAS:528:DyaK28XitlCmsbw%3D Occurrence Handle8613957

    CAS  PubMed  Google Scholar 

  39. W Martin KM Drazan AC Newby (1989) ArticleTitleMethylene blue but not changes in cyclic GMP inhibits resting and bradykinin-stimulated production of prostacyclin by pig aortic endothelial cells Br J Pharmacol 97 51–56 Occurrence Handle1:CAS:528:DyaL1MXktVWnsbc%3D Occurrence Handle2541859

    CAS  PubMed  Google Scholar 

  40. B Mayer F Brunner K Schmidt (1993) ArticleTitleInhibition of nitric oxide synthesis by methylene blue Biochem Pharmacol 45 367–374 Occurrence Handle10.1016/0006-2952(93)90072-5 Occurrence Handle1:CAS:528:DyaK3sXhtl2rs70%3D Occurrence Handle7679577

    Article  CAS  PubMed  Google Scholar 

  41. SE Rickard LJ Orcheson MM Seidl L Luyengi HH Fong LU Thompson (1996) ArticleTitleDose-dependent production of mammalian lignans in rats and in vitro from the purified precursor secoisolariciresinol diglycoside in flaxseed J Nutr 126 2012–2019 Occurrence Handle1:CAS:528:DyaK28Xks1Giurg%3D Occurrence Handle8759374

    CAS  PubMed  Google Scholar 

  42. K Prasad (2000) ArticleTitleAntioxidant activity of secoisolariciresinol diglucoside-derived metabolites, secoisolariciresinol, enterodiol, and enterolactone Int J Angiol 9 220–225 Occurrence Handle10.1007/s005470000038 Occurrence Handle11062311

    Article  PubMed  Google Scholar 

  43. RF Furchgott JV Zawadzki (1980) ArticleTitleThe obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetyl–choline Nature 288 373–376 Occurrence Handle1:CAS:528:DyaL3MXhtFCktbY%3D Occurrence Handle6253831

    CAS  PubMed  Google Scholar 

  44. LJ Ignarro GM Buga KS Wood RE Byrns G Chaudhari (1987) ArticleTitleEndothelium-derived relaxing factor produced and released from artery and vein is nitric oxide Proc Natl Acad Sci USA 84 9265–9269 Occurrence Handle1:CAS:528:DyaL1cXht12hsr8%3D Occurrence Handle2827174

    CAS  PubMed  Google Scholar 

  45. LJ Ignarro RG Harbison KS Wood PJ Kadowitz (1986) ArticleTitleActivation of purified soluble guanylate cyclase by endothelial-derived relaxing factor from intrapulmonary artery and vein: Stimulation by acetylcholine, bradykinin and arachidonic acid J Pharmacol Exp Ther 237 893–900 Occurrence Handle1:CAS:528:DyaL28Xkslehu7Y%3D Occurrence Handle2872327

    CAS  PubMed  Google Scholar 

  46. W Martin DG White AH Henderson (1988) ArticleTitleEndothelium-derived relaxing factor and atriopeptin II elevate cyclic GMP levels in pig aortic endothelial cells Br J Pharmacol 93 229–239 Occurrence Handle1:CAS:528:DyaL1cXhsVOqsrw%3D Occurrence Handle2894877

    CAS  PubMed  Google Scholar 

  47. LJ Ignarro PJ Kadowitz (1985) ArticleTitlePharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation Ann Rev Pharmacol Toxicol 25 171–191 Occurrence Handle10.1146/annurev.pa.25.040185.001131 Occurrence Handle1:STN:280:BiqB38zpsF0%3D

    Article  CAS  Google Scholar 

  48. LJ Ignarro H Lippton JC Edwards WH Baricos AI Hyman PJ Kadowitz CA Gruetter (1981) ArticleTitleMechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside, and nitric oxide: Evidence for the involvement of S-nitrosothiols as active intermediates J Pharmacol Exp Ther 218 739–749 Occurrence Handle1:CAS:528:DyaL3MXltVymsrg%3D Occurrence Handle6115052

    CAS  PubMed  Google Scholar 

  49. DD Rees RM Palmer S Moncada (1989) ArticleTitleRole of endothelium-derived nitric oxide in the regulation of blood pressure Proc Natl Acad Sci USA 86 3375–3378 Occurrence Handle1:CAS:528:DyaL1MXit12hsbo%3D Occurrence Handle2497467

    CAS  PubMed  Google Scholar 

  50. M Feelisch (1991) ArticleTitleThe biochemical pathways of nitric oxide formation from nitrovasodilators: appropriate choice of exogenous NO donors and aspects of preparation and handling of aqueous NO solution J Cardiovasc Pharmacol 17 IssueIDSuppl 3 S25–S33 Occurrence Handle1:CAS:528:DyaK3MXks1ertbo%3D Occurrence Handle1715480

    CAS  PubMed  Google Scholar 

  51. SA Waldman F Murad (1988) ArticleTitleBiochemical mechanisms underlying vascular smooth muscle relaxation: The cyclase-cyclic GMP system J Cardiovasc Pharmacol 12 IssueIDSuppl. 5 S115–S118 Occurrence Handle1:CAS:528:DyaL1MXltFentQ%3D%3D Occurrence Handle2469867

    CAS  PubMed  Google Scholar 

  52. CK Mittal F Murad (1977) ArticleTitleActivation of guanylate cyclase with superoxide dismutase and hydroxyl radical, a physiological regulator of cyclic GMP formation Proc Natl Acad Sci USA 74 4360–4364 Occurrence Handle1:CAS:528:DyaE1cXit12h Occurrence Handle22077

    CAS  PubMed  Google Scholar 

  53. K Prasad LA Bharadwaj (1996) ArticleTitleHydroxyl radical—a mediator of acetylcholine-induced vascular relaxation J Mol Cell Cardiol 28 2033–2041 Occurrence Handle10.1006/jmcc.1996.0196 Occurrence Handle1:CAS:528:DyaK28Xmt1Wrurg%3D Occurrence Handle8899562

    Article  CAS  PubMed  Google Scholar 

  54. LA Bharadwaj K Prasad (1997) ArticleTitleMechanism of hydroxyl radical-induced modulation of vascular tone Free Radic Biol Med 22 381–390 Occurrence Handle10.1016/S0891-5849(96)00325-5 Occurrence Handle1:CAS:528:DyaK2sXitFGkug%3D%3D Occurrence Handle8981029

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author acknowledges the technical assistance of Ms. Barbara Raney and Dr. Paul Lee. This work was supported by grants from the Saskatchewan Flax Development Commission and the Canadian Adaptation and Rural Development Commission.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kailash Prasad M.D., Ph.D., F.R.C.P.C., F.A.C.C., F.I.C.A..

About this article

Cite this article

Prasad, K. Antihypertensive Activity of Secoisolariciresinol Diglucoside (SDG) Isolated from Flaxseed: Role of Guanylate Cyclase. International Journal of Angiology 13, 7–14 (2004). https://doi.org/10.1007/s00547-004-1060-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00547-004-1060-4

Keywords

Navigation