EFFECT OF iNTERACTION BETWEEN TWO CALCIMIMETIC DRUGS; NIFEDIPINE AND gENTAMICIN ON SOME CARDIOVASCULAR PREPARATIONS IN EXPERIMENTAL ANIMALS

Main Article Content

Amira Mohamed Ibrahim Abd El Hameed
Omaima Mohamed Hassan
Hanan Ahmed Abd Almohymen ALfiky

Keywords

CaSR agonists, Nifedipine, Gentamicin, Cardiovascular parameters, Dose-dependent response.

Abstract

This study examines the effects of CaSR agonists, specifically nifedipine and gentamicin, on different cardiovascular parameters using both in-vitro and in-vivo trials. Gentamicin demonstrated a dose-dependent decrease in myocardial contraction amplitudes in isolated perfused rabbit hearts. Additionally, it suppressed basal tone and lowered NE-precontracted strip amplitudes in aortic strips. Gentamicin enhanced the cholinomimetic impact of acetylcholine, while suppressing the sympathomimetic impact of isoprenaline and norepinephrine, as well as the stimulating effects of histamine, serotonin, and Ca2+-gluconate.


The interaction trials between gentamicin and nifedipine demonstrated a notable decrease in the amplitudes of cardiac contractions as compared to the use of gentamicin alone. In in-vivo trials on anaesthetized rats, gentamicin elicited a dose-dependent drop in arterial blood pressure and an increase in heart rate. The coadministration of gentamicin with nifedipine led to a more significant decrease in blood pressure and heart rate, accompanied by cardiac ischemia alterations in electrocardiograms.


The results em


phasize the cardiac inhibitory, vasorelaxant, and hypotensive properties of gentamicin, as well as its ability to potentially cause heart ischemic alterations. The combination of nifedipine and gentamicin led to acute cardiovascular failure and widespread ischemia alterations. Exercise caution when administering them together, with particular emphasis on the necessity for meticulous dosage modification and ongoing monitoring of blood pressure and electrocardiogram (ECG). This study emphasizes the necessity for more research to gain a deeper comprehension of the function of calcimimetics in the cardiovascular system and guarantee their secure implementation in the treatment of heart disease.

Abstract 128 | PDF Downloads 31

References

1. Pickersgill SJ, Msemburi WT, Cobb L, Ide N, Moran AE, Su Y, Xu X, Watkins DA. Modeling global 80-80-80 blood pressure targets and cardiovascular outcomes. Nat. Med 2022 8:1693-9.
2. Striessnig J, Ortner NJ. Ca2+ channel blockers. In Encyclopedia of Molecular Pharmacology. Cham: Springer International Publishing, 2022.
3. DiVall MV, Woolley AB. CHAPTER Pharmacologic Agents. Acute Care Handbook for Physical Therapists E-Book. 2019.
4. Wang J, McDonagh DL, Meng L. Calcium channel blockers in acute care: the links and missing links between hemodynamic effects and outcome evidence. AM J CARDIOVASC DRUG 2021; 21:35-49.
5. Larson RC, Maus MV. Recent advances and discoveries in the mechanisms and functions of CAR T cells. Nat. Rev. Cancer2021;3:145-61.
6. An S. The emerging role of extracellular Ca2+ in osteo/odontogenic differentiation and the involvement of intracellular Ca 2+ signaling: from osteoblastic cells to dental pulp cells and odontoblasts. J. Cell. Physiol 2019;3:2169-93.
7. Zhou DR, Eid R, Miller KA, Boucher E, Mandato CA, Greenwood MT. Intracellular second messengers mediate stress inducible hormesis and Programmed Cell Death: A review. Biochim Biophys Acta Mol Cell Res BBA-MOL CELL RES 2019;5:773-92.
8. Foster JR, Tinwell H, Melching-Kollmuss S. A review of species differences in the control of, and response to, chemical-induced thyroid hormone perturbations leading to thyroid cancer. Arch. Toxicol 2021; 3:807-36.
9. Kim DH, Lee YH, Sayed AE, Choi IY, Lee JS. Genome-wide identification of 194 G protein-coupled receptor (GPCR) genes from the water flea Daphnia magna. Comparative Biochemistry and Physiology Part D: Genom. Proteom 2022;42:100983.
10. Cianferotti L, Romagnoli C, Brandi ML. Sensing Calcium Levels: The Biology of the Parathyroid Cells. InCellular Endocrinology in Health and Disease.Academic Press. 2021.
11. Brown AJ, Zhong M, Finch J, Ritter C, McCracken R, Morrissey J, Slatopolsky E. Rat calcium-sensing receptor is regulated by vitamin D but not by calcium. Am. J. Physiol. Renal Physiol 1996; 3:F454-60.
12. Zakir M, Ahuja N, Surksha MA, Sachdev R, Kalariya Y, Nasir M, Kashif M, Shahzeen F, Tayyab A, moazzam Khan MS, Junejo M. Cardiovascular complications of diabetes: from microvascular to macrovascular pathways. Cureus. 2023;15(9).
13. Simões LO, Alves QL, Camargo SB, Araújo FA, Hora VR, Jesus RL, Barreto BC, Macambira SG, Soares MB, Meira CS, Aguiar MC. Cardiac effect induced by Crotalus durissus cascavella venom: Morphofunctional evidence and mechanism of action. Toxicol. Lett. 2021;337:121-33.
14. Çakmak T. Exploring the impacts of pycnogenol on pentraxin-3 levels in the heart tissue of rats administered with gentamicin. Anatolian Current Medical Journal 2023;4:317-22.
15. Adams HR. Cardiovascular depressant effects of neomycin and gentamicin in rhesus monkeys. Br. J. Pharmacol. 1975;4:453.
16. Gotanda K, Yanagisawa T, Satoh K, Taira N. Are the cardiovascular effects of gentamicin similar to those of calcium antagonists?. JPN J PHARMACOL 1988;3:217-27.
17. Hashimoto H, Yanagisawa T, Taira N. Differential antagonism of the negative inotropic effect of gentamicin by calcium ions, Bay K 8644 and isoprenaline in canine ventricular muscle: comparison with cobalt ions. Br. J. Pharmacol. 1989; 4:906-12.
18. Man KN, Bartels P, Henderson PB, Kim K, Shi M, Zhang M, Ho SY, Nieves-Cintron M, Navedo MF, Horne MC, Hell JW. α1-Adrenergic receptor–PKC–Pyk2–Src signaling boosts L-type Ca2+ channel CaV1. 2 activity and long-term potentiation in rodents. eLife. 2023;12.
19. SESSION AP. XXXI ANNUAL CONFERENCE OF INDIAN PHARMACOLOGICAL SOCIETY DECEMBER 18-20, 1998, LUCKNOW. Indian Journal of Pharmacologyo 1999;31:41-80.
20. Krenn M, Grisold A, Wohlfarth P, Rath J, Cetin H, Koneczny I, Zimprich F. Pathomechanisms and clinical implications of myasthenic syndromes exacerbated and induced by medical treatments. Front. Mol. Neurosci. 2020 Aug 14;13:156.
21. Schreckenberg R, Schlüter KD. Calcium sensing receptor expression and signalling in cardiovascular physiology and disease. Vascul. Pharmacol 2018;107:35-42.
22. Magyar T, Árpádffy-Lovas T, Pászti B, Tóth N, Szlovák J, Gazdag P, Kohajda Z, Gyökeres A, Györe B, Gurabi Z, Jost N. Muscarinic agonists inhibit the ATP-dependent potassium current and suppress the ventricle–Purkinje action potential dispersion. Can. J. Physiol. Pharmacol 2021;2:247-53.
23. Martinou JC, Wollheim MP. The role of glutamate synthesis and release mechanisms in hormone secretion of pancreatic islet cells.
24. Liu M, Xue Y, Liang Y, Xue Y, Han X, Li Z, Chu L. Mechanisms underlying the cardioprotection of YangXinDingJi capsule against myocardial ischemia in rats. eCAM. 2020;1-6.
25. Jomova K, Makova M, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, Rhodes CJ, Valko M. Essential metals in health and disease. Chem. Biol. Interact 2022; 22:110173.
26. Mousavinasab SR, Akhoundi-Meybodi Z, Mahmoudi L, Karimzadeh I. A randomized double-blinded placebo-controlled clinical trial on protective effects of pentoxifylline on gentamicin nephrotoxicity in infectious patients. Clin. Exp. Nephrol 2021;25:844-53.
27. Kozuch PL, Brandt LJ. diagnosis and management of mesenteric ischaemia with an emphasis on pharmacotherapy. AP&T 2005; 3:201-15.

Most read articles by the same author(s)