Cardiovascular actions of a novel NO‐independent guanylyl cyclase stimulator, BAY 41‐8543: in vivo studies
Open accessAbstract
BAY 41‐8543 is a novel non‐NO‐based stimulator of sGC. This study investigates the acute effects of BAY 41‐8543 on haemodynamics in anaesthetized rats and dogs, its long‐term effects in conscious hypertension rat models and its antiplatelet effects. In anaesthetized dogs, intravenous injections of BAY 41‐8543 (3–100 μg kg−1) caused a dose‐dependent decrease in blood pressure and cardiac oxygen consumption as well as an increase in coronary blood flow and heart rate. In anaesthetized normotensive rats, BAY 41‐8543 produced a dose‐dependent and long‐lasting blood pressure lowering effect after intravenous (3–300 μg kg−1) and oral (0.1–1 mg kg−1) administration. A dose‐dependent and long‐lasting decrease in blood pressure was also observed in conscious spontaneously hypertensive rats with a threshold dose of 0.1 mg kg−1 p.o. After 3 mg kg−1 the antihypertensive effect lasted for nearly 24 h. After multiple dosages, BAY 41‐8543 did not develop tachyphylaxis in SHR. BAY 41‐8543 prolonged the rat tail bleeding time and reduced thrombosis in the FeCl 3 thrombosis model after oral administration. In a low NO, high renin rat model of hypertension, BAY 41‐8543 prevented the increase in blood pressure evoked by L‐NAME and reveals a kidney protective effect. In this model, the overall beneficial effects of BAY 41‐8543 manifested as both antiplatelet effect and vasodilatation were reflected in a significant reduction in mortality. The pharmacological profile of BAY 41‐8543 suggests therefore that this compound has the potential to be an important research tool for in vivo investigations in the sGC/cGMP field and it also has the potential of being a unique clinical utility for treatment of cardiovascular diseases. British Journal of Pharmacology (2002) 135, 344–355; doi:10.1038/sj.bjp.0704483
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mitochondrial enzymes beyond the ETC-pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and monoamine oxygenase A and B-have been reported to generate ROS.
“Pyruvate dehydrogenase (887), α-ketoglutarate dehydrogenase (130, 887, 952), and monoamine oxygenase A and B (290) have all been demonstrated to serve as ROS sources.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [887]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Nitric oxide: physiology, pathophysiology, and pharmacology.
Moncada, S., Palmer, R. M., & Higgs, E. A. (1991) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06663-3 · Cited by 15,525 · see citing works
Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man
Vallance, P., Collier, J., & Moncada, S. (1989) · The Lancet · doi:10.1016/s0140-6736(89)91013-1 · Cited by 1,590 · see citing works
CARTER, V. B. (1951) · PubMed · Cited by 741 · see citing works
Stone, J. R., & Marletta, M. A. (1994) · Biochemistry · doi:10.1021/bi00184a036 · Cited by 647 · see citing works
NO-independent regulatory site on soluble guanylate cyclase
Stasch, J., Becker, E. M., Alonso‐Alija, C., Apeler, H., Dembowsky, K., Feurer, A., Gerzer, R., Minuth, T., Perzborn, E., Pleiß, U., et al. (2001) · Nature · doi:10.1038/35065611 · Cited by 546 · see citing works
Self-citationRat model of arterial thrombosis induced by ferric chloride
Kurz, K. D., Main, B. W., & Sandusky, G. E. (1990) · Thrombosis Research · doi:10.1016/0049-3848(90)90106-m · Cited by 431 · see citing works
YC-1, a novel activator of platelet guanylate cyclase
Ko, F., Wu, C., Sc, K., Lee, F., & Teng, C. (1994) · Blood · doi:10.1182/blood.v84.12.4226.bloodjournal84124226 · Cited by 402 · see citing works
Murad, F. (1999) · Angewandte Chemie International Edition · doi:10.1002/(sici)1521-3773(19990712)38:13/14 · Cited by 381 · see citing works
Sensitizing soluble guanylyl cyclase to become a highly CO‐sensitive enzyme.
Friebe, A., Schultz, G., & Koesling, D. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01078.x · Cited by 352 · see citing works
The use of nitric oxide donors in pharmacological studies
Feelisch, M. (1998) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/pl00005231 · Cited by 348 · see citing works
Münzel, T. F., Kurz, S. D., Rajagopalan, S., Thoenes, M., Berrington, W. R., Thompson, J. A., Freeman, B. Α., & Harrison, D. G. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118935 · Cited by 313 · see citing works
Chronic Nitric Oxide Inhibition Model Six Years On
Zatz, R., & Baylis, C. (1998) · Hypertension · doi:10.1161/01.hyp.32.6.958 · Cited by 257 · see citing works
Mülsch, A., Bauersachs, J. K., Schäfer, A., Stasch, J., Kast, R., & Busse, R. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0700982 · Cited by 222 · see citing works
Self-citationWu, C., Ko, F., Kuo, S., Lee, F., & Teng, C. (1995) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1995.tb16400.x · Cited by 197 · see citing works
Galle, J., Zabel, U., Hübner, U., Hatzelmann, A., Wagner, B., Wanner, C., & Schmidt, H. H. H. W. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702495 · Cited by 173 · see citing works
YC-1 Potentiates Nitric Oxide- and Carbon Monoxide-Induced Cyclic GMP Effects in Human Platelets
Friebe, A., Müllershausen, F., Smolenski, A., Walter, U., Schultz, G., & Koesling, D. (1998) · Molecular Pharmacology · doi:10.1124/mol.54.6.962 · Cited by 167 · see citing works
NO-Independent stimulators of soluble guanylate cyclase
Straub, A., Stasch, J., Alonso‐Alija, C., Benet‐Buchholz, J., Ducke, B., Feurer, A., & Fürstner, C. (2001) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(01)00073-7 · Cited by 149 · see citing works
Self-citationMülsch, A., Oelze, M. W., Klöss, S., Mollnau, H., Töpfer, A., Smolenski, A., Walter, U., Stasch, J., Warnholtz, A., Hink, U., et al. (2001) · Circulation · doi:10.1161/01.cir.103.17.2188 · Cited by 133 · see citing works
Self-citationStasch, J., Alonso‐Alija, C., Apeler, H., Dembowsky, K., Feurer, A., Minuth, T., Perzborn, E., Schramm, M., & Straub, A. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704484 · Cited by 132 · see citing works
Self-citationHoenicka, M., Becker, E., Apeler, H., Sirichoke, T., Schröder, H., Gerzer, R., & Stasch, J. (1999) · Journal of Molecular Medicine · doi:10.1007/s001090050292 · Cited by 112 · see citing works
Self-citationMorton, J. J., Beattie, E. C., Speirs, A., et al. (1993) · Journal of Hypertension · doi:10.1097/00004872-199310000-00012 · Cited by 91 · see citing works
Teng, C., Wu, C., Ko, F., et al. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(96)00911-9 · Cited by 87 · see citing works
Navarro, J., Sánchez, A., Saiz, J., Ruilope, L. M., García‐Estañ, J., Romero, J. C., Moncada, S., & Lahera, V. (1994) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1994.267.6.r1516 · Cited by 72 · see citing works
Straub, A. (2002) · Bioorganic & Medicinal Chemistry · doi:10.1016/s0968-0896(02)00034-2 · Cited by 65 · see citing works
Absolute quantitation of coronary steal induced by intravenous dipyridamole
Akinboboye, O. O., Idris, O., Chou, R.-L., et al. (2001) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)01041-x · Cited by 58 · see citing works
Rothermund, L., Friebe, A., Paul, M., et al. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703320 · Cited by 55 · see citing works
Becker, E. M., Schmidt, P. M., Schramm, M., Schröder, H., Walter, U., Hoenicka, M., Gerzer, R., & Stasch, J. (2000) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-200003000-00007 · Cited by 34 · see citing works
Self-citationHobbs, A. J. (2000) · Emerging Therapeutic Targets · doi:10.1517/14728222.4.6.735 · Cited by 29 · see citing works
Renal effects of captopril and nitrendipine in transgenic rats with an extra renin gene.
Hirth‐Dietrich, C., Stasch, J.-P., Ganten, D., et al. (1994) · Hypertension · doi:10.1161/01.hyp.23.5.626 · Cited by 26 · see citing works
Self-citationEffect of molsidomine on cardiac preload, coronary artery diameter, and coronary resistance
Bassenge, E., & Pohl, U. (1985) · American Heart Journal · doi:10.1016/0002-8703(85)90667-2 · Cited by 16 · see citing works
Nitrate tolerance in angina pectoris
Parker, J. O. (1989) · Cardiovascular Drugs and Therapy · doi:10.1007/bf00133214 · Cited by 13 · see citing works
Gardiner, S. M., March, J. E., Kemp, P. A., et al. (1998) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701838 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- BUSSE, W.D. & SEUTER, F. (1981). Zur Wirkung von Acetylsali- cylsaÈ ure, Dipyridamol und Sul®npyrazon in verschiedenen Thrombosemodellen. In Thrombosemodelle am Tier. ed. Breddin, K., Gross, D., Rotter, W. pp. 157 ± 171. Schattauer Verlag, Stuttgart.
- Bergmeyer, H.U. Vol. II. pp. 1842 ± 1846, Verlag Chemie, Weinheim, Germany.
- STRAUB, A., FEURER, A., ALONSI-ALIJA, C., STASCH, J.-P., PERZ- BORN, E., HU È TTER, J., DEMBOWSKY, K. & STAHL, E. (1998). Substituted pyrazole derivatives condensed with six-membered heterocyclic rings. WO 2,000,006,568 (2000). Chem. Abstr., 132, 122629. (2000)
Cited by
Sorted by citations
Strategies to increase nitric oxide signalling in cardiovascular disease
Lundberg, J. O., Gladwin, M. T., & Weitzberg, E. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4623 · Cited by 576 · see citing works
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541 · see citing works
Münzel, T., Feil, R., Mülsch, A., Lohmann, S. M., Hofmann, F., & Walter, U. (2003) · Circulation · doi:10.1161/01.cir.0000094403.78467.c3 · Cited by 316 · see citing works
Reactive Oxygen-Related Diseases: Therapeutic Targets and Emerging Clinical Indications
Casas, A. I., Dao, V. T.-V., Daiber, A., Maghzal, G. J., Di Lisa, F., Kaludercic, N., Leach, S., Cuadrado, A., Jaquet, V., Seredenina, T., et al. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6433 · Cited by 136 · see citing works
Role of sGC-dependent NO signalling and myocardial infarction risk
Wobst, J., Kessler, T., Dang, T. A., Erdmann, J., & Schunkert, H. (2015) · Journal of Molecular Medicine · doi:10.1007/s00109-015-1265-3 · Cited by 28 · see citing works
- Authors
- Stasch, J., Dembowsky, K., Perzborn, E., Stahl, E., & Schramm, M.
- Affiliations
- Bayer (Germany) (DE)
- Corresponding author
- Stasch, Johannes‐Peter
- ORCID
- Schramm, Matthias
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2002-01
- Volume
- 135
- Issue
- 2
- Pages
- 344-355
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1573146
- OpenAlex
- W1988711065
- Cited by
- 120
- References
- 32
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 3 · 2015: 11 · 2014: 3 · 2013: 13 · 2012: 9
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- antihypertensive effect, spontaneously hypertensive rats, antiplatelet activity, hemodynamics, coronary blood flow, myocardial oxygen consumption, tachyphylaxis, renin-angiotensin system, L-NAME, renal protection, vasodilation, bleeding time, thrombosis
- MeSH terms
- Animals, Blood Pressure, Cardiovascular System, Dogs, Dose-Response Relationship, Drug, Female, Guanylate Cyclase, Hemodynamics, Male, Morpholines, Nitric Oxide, Pyrimidines, Rats, Inbred SHR, Rats, Wistar, Enzyme Activators, Animals, Genetically Modified, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
