Vazorelaksantna svojstva novih benzodiazepinima-sličnih liganada na izolovanoj torakalnoj aorti pacova

  • Milica Gajić Bojić Centar za biomedicinska istraživanja, Medicinski fakultet Univerziteta u Banjoj Luci
  • Miroslav Savić Zavod za farmakologiju, Farmaceutski fakultet, Univerzitet u Beogradu

Sažetak


Background/Aim: Intravitreal drug injection cause an increase in intraocular pressure (IOP). The increase in IOP is directly proportional to the volume of drug injected into the eye and inversely to the vitreal reflux. The mixture of fluid, presents as a subconjunctival bleb, composed of vitreous and injected drug is called vitreal reflux. In this study changes in IOP after intravitreal injection of bevacizumab in relation to the vitreous regurgitation were observed.

Methods: This prospective study involved 50 patients (57 injections). Bevacizumab was administered intravitreally at a dose of 1.25 mg/0.05 mL. According to the type of disease, patients with diabetic macular oedema, proliferative diabetic retinopathy, age-related macular degeneration, retinal vein occlusion, choroidal neovascularisation and central serous chorioretinopathy were included. They were divided into two groups – the first one without vitreal reflux and the second one with vitreal reflux. IOP values were measured at baseline, right after drug application and 20 min thereafter.

Results: The reference value range of IOP values were 10-21 mmHg and so were the average baseline values in both experimental groups of patients (15.81 ± 3.50 mmHg). In the experimental group without reflux post application mean values of IOP at 0 and 20 min were 50 ± 9.65 and 18.54 ± 5.06 mmHg, respectively. In the experimental group with reflux post application mean IOP values after 0 and 20 min were 36 ± 8.68 mmHg and 18.91 ± 4.82 mmHg, respectively.

Conclusions: Following intravitreal bevacizumab application, a significant increase in IOP occurs. After 20 minutes the IOP values spontaneously decreased below 25 mmHg in both groups and there was no significant difference in comparison with the baseline values. Vitreus reflux is a major factor in short-term post-injection IOP elevation, but not from the longer-term perspective.

Reference

Literature

1. Billingley M, Suria A, Gilman R, Shokes L, Shahvari M. Evidence for GABA involvement in the peripheral control of blood pressure and vascular resistance. Brain Research Bulletin 1980; Vol 5 Supp2;329-333
2. Lim DY, Suh J, Yoo HJ, Kim WS, Kim SB, Lee SK, Lee SI, Hong SP. Influence of gamma-aminobutyric acid on the changes of blood pressure in rats. Korean J Intern Med. 1990 Jan; 5(1):23-33. PubMed PMID: 2271508; PubMed Central PMCID: PMC4534999.
3. Fujiwara M, Muramatsu I, Shibata S. γ-Aminobutyric acid receptor on vascular smooth muscle of dog cerebral arteries. Br J Pharmacol. 1975 Dec; 55(4):561-2. PubMed PMID: 1212564; PubMed Central PMCID: PMC1666743.
4. Edvinsson L, Krause DN. Pharmacological characterization of GABA receptors mediating vasodilation of cerebral arteries in vitro. Brain Res. 1979 Sep 7; 173(1):89-97. PubMed PMID: 226209.
5. Akinci MK, Schofield PR. Widespread expression of GABA(A) receptor subunits in peripheral tissues. Neurosci Res. 1999 Nov; 35(2):145-53. PubMed PMID: 10616918.
6. Takano K, Yatabe MS, Abe A, Suzuki Y, Sanada H, Watanabe T, Kimura J, Yatabe J. Characteristic expressions of GABA receptors and GABA producing/transporting molecules in rat kidney. PLoS One. 2014 Sep 4;9(9):e105835. doi: 10.1371/journal.pone.0105835. eCollection 2014. PubMed PMID: 25188493; PubMed Central PMCID: PMC4154856.
7. Hamel E, Krause DN, Roberts E. Specific cerebrovascular localization of glutamate decarboxylase activity. Brain Res. 1981 Oct 26;223(1):199-204. PubMed PMID: 7284804.
8. Sen S, Roy S, Bandyopadhyay G, Scott B, Xiao D, Ramadoss S, Mahata SK, Chaudhuri G. γ-Aminobutyric Acid Is Synthesized and Released by the Endothelium: Potential Implications. Circ Res. 2016 Aug 19;119(5):621-34. doi: 10.1161/CIRCRESAHA.116.308645. Epub 2016 Jun 28. PubMed PMID: 27354210.
9. Galindo A, Vargas ML, Estan JG, Fuentes T, Hernandez J. Synergistic interaction of diazepam with 3',5'-cyclic adenosine monophosphate-elevating agents on rat aortic rings. Eur J Pharmacol. 2001 Oct 5;428(2):269-75. PubMed PMID: 11675045.
10. Park SE, Sohn JT, Kim C, Chang KC, Shin IW, Park KE, et al. Diazepam attenuates phenylephrine-induced contractions in rat aorta. Anesth Analg. 2006 Mar;102(3):682-9. PubMed PMID: 16492815.
11. Colussi GL, Fabio AD, Catena C, Chiuch A, Sechi LA. Involvement of endothelium-dependent and –independent mechanisms in midazolam-induced vasodilation. Hypertens Res. 2011 Aug; 34(8):929-34. doi: 10.1038/hr.2011.62. Epub 2011 May 26. PubMed PMID: 21614005.
12. Jacob MK, White RE. Diazepam, gamma-aminobutyric acid, and progesterone open K(+) channels in myocytes from coronary arteries. Eur J Pharmacol. 2000 Sep 8;403(3):209-19. PubMed PMID: 10973621.
13. Prevot TD, Li G, Vidojevic A, Misquitta KA, Fee C, Santrac A, Knutson DE,Stephen MR, Kodali R, Zahn NM, Arnold LA, Scholze P, Fisher JL, Marković BD,Banasr M, Cook JM, Savic M, Sibille E. Novel Benzodiazepine-Like Ligands with Various Anxiolytic, Antidepressant, or Pro-Cognitive Profiles. Mol Neuropsychiatry. 2019 Apr;5(2):84-97. doi: 10.1159/000496086. Epub 2019 Jan 23. PubMed PMID: 31192221; PubMed Central PMCID: PMC6528097.
14. Rizvić E, Janković G, Savić M. Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant. Korean J Physiol Pharmacol 2017;21(4):385-395
15. Jespersen B, Tykocki NR, Watts SW, Cobbett PJ. Measurement of smooth muscle function in the isolated tissue bath-applications to pharmacology research. J Vis Exp. 2015 Jan 19;(95):52324. doi: 10.3791/52324. PubMed PMID: 25650585; PubMed Central PMCID: PMC4354551.
16. Seifi M, Brown JF, Mills J, Bhandari P, Belelli D, Lambert JJ, Rudolph U, Swinny JD. Molecular and functional diversity of GABA-A receptors in the enteric nervous system of the mouse colon. J Neurosci. 2014 Jul 30;34(31):10361-78. doi: 10.1523/JNEUROSCI.0441-14.2014. PubMed PMID: 25080596; PubMed Central PMCID: PMC4115141.
17. Mizuta K, Xu D, Pan Y, Comas G, Sonett JR, Zhang Y, Panettieri RA Jr, Yang J, Emala CW Sr. GABAA receptors are expressed and facilitate relaxation in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2008 Jun;294(6):L1206-16. doi:10.1152/ajplung.00287.2007. Epub 2008 Apr 11. PubMed PMID: 18408071; PubMed Central PMCID: PMC3647697.
18. Forkuo GS, Guthrie ML, Yuan NY, Nieman AN, Kodali R, Jahan R, Stephen MR,Yocum GT, Treven M, Poe MM, Li G, Yu OB, Hartzler BD, Zahn NM, Ernst M, Emala CW,Stafford DC, Cook JM, Arnold LA. Development of GABAA Receptor Subtype-Selective Imidazobenzodiazepines as Novel Asthma Treatments. Mol Pharm. 2016 Jun 6;13(6):2026-52. doi: 10.1021/acs.molpharmaceut.6b00159. Epub 2016 May 10. PubMed PMID: 27120014; PubMed Central PMCID: PMC4899155.
19. Korol SV, Jin Z, Jin Y, Bhandage AK, Tengholm A, Gandasi NR, Barg S, Espes D, Carlsson PO, Laver D, Birnir B. Functional Characterization of Native, High-Affinity GABA(A) Receptors in Human Pancreatic β Cells. EBioMedicine. 2018 Apr;30:273-282. doi: 10.1016/j.ebiom.2018.03.014. Epub 2018 Mar 22. PubMed PMID: 29606630; PubMed Central PMCID: PMC5952339.
20. Hong SJ, Damron DS, Murray PA. Benzodiazepines differentially inhibit phenylephrine-induced calcium oscillations in pulmonary artery smooth muscle cells. Anesthesiology. 1998 Mar;88(3):792-9. PubMed PMID: 9523825.
21. Perusquía M, Hernández R, Morales MA, Campos MG, Villalón CM. Role of endothelium in the vasodilating effect of progestins and androgens on the rat thoracic aorta. Gen Pharmacol. 1996 Jan;27(1):181-5. PubMed PMID: 8742519.
22. Farsi L, Keshavarz M, Soltani N. Relaxatory effect of gamma-aminobutyric acid (GABA) is mediated by same pathway in diabetic and normal rat mesenteric bed vessel. Iran J Bas Med Sci. 2011;14(1):94-8.
23. Kharazmi F, Soltani N, Rezaei S, Keshavarz M, Farsi L. Role of GABAB receptor and L-Arg in GABA-induced vasorelaxation in non-diabetic and streptozotocin-induced diabetic rat vessels. Iran Biomed J. 2015;19(2):91-5.PubMed PMID: 25864813; PubMed Central PMCID: PMC4412919.
24. Sigel E, Ernst M. The Benzodiazepine Binding Sites of GABA(A) Receptors. Trends Pharmacol Sci. 2018 Jul;39(7):659-671. doi: 10.1016/j.tips.2018.03.006. Epub 2018 Apr 30. Review. PubMed PMID: 29716746.
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2020/06/30
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