ROLE OF THROMBOXANE AND LEUKOTRIENES IN MECHANISMS OF CONTRACTILE REACTIONS OF PORTAL VEIN, INDUCED BY ACETYLCHLINE AND PHENYLEPHRINE
O.O. Vinogradova, P.I. Yanchuk, O.M. Pasichnichenko
NSC "Institute of Biology" Shevchenko Kyiv National University
Effects of picotamide and zileuton on tonic contractile activity
of the rat portal vein preparations, induced by acetylcholine
mol/l) and phenylephrine (5∙10-7
mol/ l) were investigated.
Conversion of arachidonic acid products (prostaglandins,
leukotrienes) synthesized by endothelial cells, plays an
important role in the local regulation of vascular tone. The
compounds formed in a cascade of enzymatic transformations
can modulate the effect of other vasoactive factors. Picotamide
mol/ l) - thromboxane receptor and thromboxane
-synthase blocker - depress acetylcholine-induction tonic
contraction of isolated segments of portal vein with intact endothelium
by 29% and norepinephrine- induction reduction of
45% relative to the control values. The obtained results indicate
a participation of thromboxane and/or endoperoxide H2 in this
reaction. Partial inhibition of the contractions by 5-lipoxygenase
blocker zileuton (4,2·10-5
mol/ l) at 23% relative to control
values suggests, that products of lipoxigenase pathways of
arachidonic acid conversion are involved in mechanisms of
specified reactions. These data indicate complex mechanisms
of regulation of vascular tone of the portal vein, which play an
important role eicosanoids. Further study of these mechanisms
is necessary for the formation of basic knowledge, as well as
to elucidate the mechanisms of occurrence and development
of pathological conditions of vessels and the development of
methods of their correction.
acetylcholine; phenylephrine; portal vein; thromboxane; leukotrienes.
- Iniguez MA, Cacheiro-Llaguno C, Cuesta N. Prostanoid function and cardiovascular disease. Arch Physiol Biochem. 2008 Jul;114(3):201-9.
- Fresno M, Diaz-Munoz M, Cuesta N. Prostanoid actions in cardiovascular physiopathology. An R Acad Farm. 2008 May;74(4):1-23.
- Smyth EM, Grosser T, Wang M. Prostanoids in health and disease. J Lipid Res. 2009 Apr; 50:S423-8.
- Graupera M, March S, Engel P. Sinusoidal endothelial COX-1-derived prostanoids modulate the hepatic vascular tone of cirrhotic rat livers. Am J Physiol Gastrointest Liver Physiol.2005 Apr; 288(4):763-70.
- Pestel S, Schlaf G, Götze O. Differences in the involvement of prostanoids from Kupffer cells in the mediation of anaphylatoxin C5a-, zymosan-, and lipopolysaccharidedependent hepatic glucose output and flow reduction. Lab Invest. 2003 Dec; 83(12):1733-41.
- Kinoshita G, Washizu M, Kondo M. The effect of indomethacin on liver blood flow and oxygen supplyuptake relationship in the dog. J Vet Med Sci. 1995 Apr; 57(2):193-7.
- Eglen R, Whiting R. The action of prostanoid receptor agonists and antagonists on smooth muscle and platelets. Br J Pharmacol. 1988 Jun; 94(2):591-601.
- Lüscher TF, Vanhoutte PM. Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertension. 1986 Apr; 8:344-8.
- Srinivasa A, Marshall JM. Effects of cyclooxygenase inhibition on vascular responses evoked in fingers of men and women by iontophoresis of 1- and 2-adrenoceptor agonists. J Physiol. 2011 Sep; 589(18):4555-64.
- Higashi Y, Sasaki S. Excess norepinephrine impairs both endothelium-dependent and -independent vasodilation in patients with pheochromocytoma. Hypertension. 2002; 39:513-18.
- Wang A, Nishihashi T, Murakami S. et al. Noradrenalineinduced contraction mediated by endothelial COX-1 metabolites in the rat coronary artery. J Cardiovasc Pharmacol. 2003 Dec; 42:S39-42.
- Roberts RE, Kendall DA, Wilson VG. α2-adrenoceptor and NPY receptor-mediated contractions of porcine isolated blood vessels: evidence for involvement of the vascular endothelium. Br J Pharmacol. 1999 Dec; 128:1705-12.
- Pasichnichenko O, Vynogradova O, Yanchuk P. Endothelium-dependent contraction of rat portal vein under the action of acetylcholine and norepinephrine. Phizyka zhіvogo. 2009;17(2):127-9 [Ukrainian].
- Yanchuk P, Vynogradova O, Pasichnichenko O, Kostenko S. Participation of eicosanoids in the mechanism of contractile responses of the portal vein to the action of adrenaline and noradrenaline. Fiziol Zh. 2013; 59(6):43-48 [Ukrainian].
- Modesti P. Picotamide: an Inhibitor of the formation and effects of TxA2. Cardiovascular Drug Reviews. 1995 Dec;13(4):353-64.
- Rapoport RM, Williams SP. Role of prostaglandins in acetylcholine-induced contraction of aorta from spontaneously hypertensive and Wistar-Kyoto rats. Hypertension. 1996 Jul; 28:64-75.
- Kurashi K, Nishihashi T, Trandafir C. Diversity of endothelium-derived vasocontracting factors arachidonic acid metabolites. Acta Pharmacol Sin. 2003 Nov; 24(11):1065-9.
- Jino H, Kurahashi K, Usui H. Possible involvement of endothelial leukotrienes in acetylcholine-induced contraction in rabbit coronary artery. Life Sci. 1996. – 59(12):961-67
© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2020.