Synergistic Effects of Dantrolene and Nimodipine on the Phenylephrine-Induced Contraction and ACh-Induced Relaxation in Aortic Rings from Diabetic Rats

International Journal of Endocrinology
Maria J CrespoJose Quidgley

Abstract

Diabetics have a higher risk of developing cerebral vasospasms (CVSP) than nondiabetics. The addition of the ryanodine receptor (RyR) blocker dantrolene to standard therapies reduces vasospasms in nondiabetics. Whether diabetics with CVSP also benefit from this drug, however, is unknown. We evaluated the effects of a 30 min incubation with dantrolene (50 μM), nimodipine (50 nM), and both drugs in combination, on phenylephrine- (PHE-) induced contraction and on acetylcholine- (ACh-) induced relaxation in aortic rings from streptozotocin (STZ) diabetic rats. Age-matched, nondiabetic rats served as controls. The oxidative stress markers malondialdehyde (MDA) and 4-hydroxyalkenal (4-HAE) were also evaluated in the presence and absence of dantrolene and nimodipine. The combination of these two drugs acted synergistically to reduce the PHE-induced contraction by 80% in both diabetics and controls. In contrast, it increased the Emax value for ACh-induced relaxation (from 56.46 ± 5.14% to 96.21 ± 7.50%; n = 6, P < 0.05), and it decreased MDA + 4-HAE values in diabetic rats only. These results suggest that the combination of dantrolene and nimodipine benefits both diabetics and nondiabetics by decreasing arterial tone synergistically.

References

Oct 24, 1995·Biochemical and Biophysical Research Communications·C B NeylonA Bobik
Mar 10, 2000·American Journal of Physiology. Heart and Circulatory Physiology·R WangS T Hanna
Mar 28, 2003·Pharmacology·María J CrespoJuan González
Dec 4, 2003·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·S U YanpallewarS B Acharya
Nov 24, 2005·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·S R R HallM Hong
Sep 16, 2006·The Journal of Biological Chemistry·Nicola PierobonAndrew P Thomas
Sep 19, 2006·The International Journal of Biochemistry & Cell Biology·Marian ValkoJoshua Telser
Feb 22, 2008·Journal of Cardiovascular Pharmacology and Therapeutics·María J CrespoLucy Arocho
May 23, 2008·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Xiao-Chen RuQiang Xia
Aug 13, 2008·Neurocritical Care·Susanne MuehlschlegelJohn R Sims
Oct 17, 2008·Neurocritical Care·Salvatore SalomoneJohn Randall Sims
Jan 20, 2009·Current Medicinal Chemistry·Maria Assunta PotenzaMonica Montagnani
May 27, 2009·European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·Adem AslanMurat Cosar
Oct 23, 2009·American Journal of Physiology. Cell Physiology·Manuel F NavedoLuis F Santana
May 7, 2010·American Journal of Physiology. Cell Physiology·Thirumalini VaithianathanAlejandro M Dopico
Oct 30, 2010·Circulation Research·Ferdinando Giacco, Michael Brownlee
Dec 12, 2012·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Fabrice DabertrandJoseph E Brayden
Oct 26, 2014·Journal of Neurology, Neurosurgery, and Psychiatry·Susanne MuehlschlegelAjay K Wakhloo
Nov 21, 2014·Handbook of Clinical Neurology·Michael D Hill
Mar 3, 2015·Genetics and Molecular Research : GMR·Y-F JiaJ Li
Sep 1, 2015·World Journal of Diabetes·María J Crespo, José Quidgley

❮ Previous
Next ❯

Methods Mentioned

BETA
MDA

Software Mentioned

LabView
GraphPad
GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.