Hypotensive effect of bi-potassium salt of 1-hexadecyl-2-methylcarbamoylphosphatidic acid in rats with renovascular hypertension
https://doi.org/10.20538/1682-0363-2018-4-163-170
Abstract
The study describes the synthesis and hypotensive effects of stable platelet activation factor (PAF) precursor 1-hexadecyl-2-m ethylcarbamoyl-phosphatidic acid (HMCP) оn outbred Wistar rats with 1-kidney 1-clip (1K1C) renovascular hypertension. Intravenous injection of 0.1, 0.5, 1 and 5 mg/kg HMCP resulted in a sharp decline of up to 50% of MAP with subsequent restoration to initial level. In some hypertensive 1K1C rats HMCP has a prolonged effect with blood pressure stabilized at 75% of initial level after 30 min post injection. HMCP was toxic at higher doses with a LD50 around 3 mg/kg.
About the Authors
N. Y. Khromova
State Research Institute of the Organic Chemistry and Technology
Russian Federation
Russian Federation
Khromova Natalia Y., PhD, Senior Researcher
23, Shosse Entuziastov, Moscow, 111024
S. I. Malekin
State Research Institute of the Organic Chemistry and Technology
Russian Federation
Russian Federation
Malekin Sergey I., DСhSc, Professor, Senior Researcher
23, Shosse Entuziastov, Moscow, 111024
S. A. Gavrilova
Lomonosov Moscow State University
Russian Federation
Russian Federation
Gavrilova Svetlana A., Associate Professor, Faculty of Fundamental Medicine
27/1, Lomonosovsky Av., 1119991, Moscow
S. V. Kotelevtsev
Lomonosov Moscow State University
Russian Federation
Russian Federation
Kotelevtsev Sergey V., DСhSc, Senior Researcher, Faculty of Biology
27/1, Lomonosovsky Av., 1119991, Moscow
Yu. V. Kotelevtsev
Research Center for Functional Genomics and Integrative Physiology, Skolkovo Institute of Science and Technology
Russian Federation
Russian Federation
Kotelevtsev Yuri V., PhD, Professor, Research Center for Functional Genomics and Integrative Physiology, Skolkovo Institute of Science and Technology
100, Novaia Str., Skolkovo, Odintsovo District, Moscow Region, 143025
References
1. https://www.credenceresearch.com/press/global-angiotensin-converting-enzyme-ace-inhibitors-market.
2. Koltai M., Hosford D., Guinot P., Esanu A., Braquet P. Platelet activating factor (PAF). A review of its effects, antagonists and possible future clinical implications (Part I). Drugs. 1991; 42 (1): 9–29.
3. Juncos L.A., Ren Y.L., Arima S., Ito S. Vasodilator and constrictor actions of platelet-activating factor in the isolated microperfused afferent arteriole of the rabbit kidney. Role of endothelium-derived relaxing factor/nitric oxide and cyclooxygenase products. J. Clin. Invest. 1993; 91(4): 1374–1379.
4. McMurtry I.F., Morris K.G. Platelet-activating factor causes pulmonary vasodilation in the rat. Am. Rev. Respir. Dis. 1986; 134 (4): 757–762.
5. Lуpez-Novoa J. M. Potential role of platelet activating factor in acute renal failure. Kidney Int. 1999; 55 (5): 1672–1682.
6. Goldstein B.M., Gabel R.A., Huggins F.J., Cervoni P., Crandall D.L. Effect of platelet activating factor (PAF) on blood flow distribution in the spontaneously hypertensive rat. Life Sci. 1984; 35 (13): 1373–1378.
7. Hubbard J.W., Cox R.H., Lawler J.E., Blank M.L., Snyder F. Cardiac output and peripheral vascular resistance during intravenous infusion of 1-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine in conscious normotensive and spontaneously hypertensive rats. Res. Commun. Chem. Pathol. Pharmacol. 1985; 49 (3): 459–462.
8. Yamanaka S., Miura K., Yukimura T., Okumura M., Yamamoto K. Putative mechanism of hypotensive action of platelet-activating factor in dogs. Circ. Res. 1992; 70 (5): 893–901.
9. Blank M.L., Cress E.A., Snyder F.A new class of antihypertensive neutral lipid: 1-Alkyl-2-acetyl-sn-glycerols, a precursor of platelet activating factor. Biochem. Biophys. Res. Commun. 1984; 118 (1): 344–350.
10. Malekin S.I., Kotelevtsev S.V., Gavrilova S.A., Fadyukova O.E., Golubeva A.V., Grinchenko M.I., Koshelev V.B., Kotelevtsev Y.V., Hamet P., Orlov S.N. Long-term normalization of blood pressure in SHR and 1-kidney 1-clip rats by synthetic precursor of stable PAF analogue without systemic effects in normotensive rats. Pathophysiol. Off. J. Int. Soc. Pathophysiol. ISP. 2011; 18 (2): 151–157. DOI: 10.1016/j.pathophys.2010.08.001.
11. Gusakova S.V., Rydchenko V.S., Smaglii L.V., Plotnikov M.B., Chernysheva G.A., Tarasova O.S., Orlov S.N. Influence of synthetic analog of plated activate factor 1-alkil-2-alkylcarbomoilglicerine on vascular smooth muscle cell contractile properties. Arterialnaia gipertonia. 2017; 23 (5): 373–382 (in Russ.).
12. Tyurin Yu.N., Makarov A.A. Statistical analysis of the data on your computer. Мoscov: INFRA Publ., 1998: 528 (in Russ.).
13. Montrucchio G., Alloatti G. & Camussi G. Role of plateletactivating factor in cardiovascular pathophysiology. Physiol. Rev. 2000; 80 (4): 1669–1699. doi.org/10.1152/physrev.2000.80.4.1669.
14. Snyder F. Platelet-аctivating factor and related lipid mediators. Springer Science & Business Media, 2013: 1–492. DOI: 10.1007/978-1-4684-5284-6.
15. Cunningham F.M. Lipid Mediators. Elsevier, 2016: 395.
16. Papakonstantinou V.D., Lagopati N., Tsilibary E.C., Demopoulos C.A., Philippopoulos A.I. A review on platelet activating b factor inhiitors: could an new class of potent metal-based anti-inflammatory drugs induce anticancer properties? Bioinorganic Chemistry and Applications. 2017: 6947034. DOI: 10.1155/2017/6947034.
17. Liu Y. et al. Current understanding of platelet-activating factor signaling in central nervous system diseases. Mol. Neurobiol. 2017; 54 (7): 5563–5572. DOI: 10.1007/s12035-016-0062-5.
Review
For citations:
Khromova N.Y., Malekin S.I., Gavrilova S.A., Kotelevtsev S.V., Kotelevtsev Yu.V. Hypotensive effect of bi-potassium salt of 1-hexadecyl-2-methylcarbamoylphosphatidic acid in rats with renovascular hypertension. Bulletin of Siberian Medicine. 2018;17(4):163-170. (In Russ.) https://doi.org/10.20538/1682-0363-2018-4-163-170
Views:
846
Email this article 