Angiotensin II enhances thrombosis development in renovascular hypertensive rats

Summary

There is an increased number of in vitro evidence that angioten-sin II (Ang II) may promote thrombosis. However there are no in vivo experiments exploring the effect of Ang II on thrombus formation. In the present study we have investigated the influence of Ang II on venous thrombosis in renovascular hypertensive rats. Furthermore, we examined the role of AT₁ receptor and Ang II metabolites: angiotensin III (Ang III) and angioten-sin IV (Ang IV) in the mechanisms of Ang II action. The contribution of coagulation and fibrinolytic systems in the mode of Ang II action was also determined. Venous thrombosis was induced by ligation of vena cava. Ang II infused into rats developing venous thrombosis caused dose-dependent increase in thrombus weight, which was partially reversed by losartan, selective AT₁ antagonist. Ang III did not influence the thrombus formation in hypertensive rats, while Ang IV caused a marked increase in thrombus weight only in one of the used doses. Our study shows that Ang II via AT₁ receptor enhances thrombosis development. The prothrombotic effect of Ang II may partially depend on enhanced leukocytes adhesion to endothelial cells accompanied by accelerated fibrin formation and increased plasma level of PAI-1. Moreover, Ang II action is partially mediated by one of its metabolites – Ang IV.

Keywords

Angiotensin - hypertensive rat - haemostasis - venous thrombosis

• References

• 1 Pfeffer MA, Braunwald E, Moye LA. et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992; 327: 669-77.
• 2 Yusuf S, Sleight P, Pogue J. et al. Effects of an angiotensin- converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 145-53.
• 3 Pitt B, Poole-Wilson PA, Segal R. et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355: 1582-7.
• 4 Pawlak R, Chabielska E, Golatowski J. et al. Nitric oxide and prostacyclin are involved in antithrombotic action of captopril in venous thrombosis in rats. Thromb Haemost 1998; 79: 1208-12.
• 5 Chabielska E, Pawlak R, Golatowski J. et al. The antithrombotic effect of captopril and losartan on experimental arterial thrombosis in rats. J Physiol Pharmacol 1998; 49: 251-60.
• 6 Griendling KK, Minieri CA, Ollerenshaw JD. et al. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 1994; 74: 1141-8.
• 7 Weiss D, Sorescu D, Taylor WR. Angiotensin II and atherosclerosis. Am J Cardiol 2001; 87: 25C-32C.
• 8 Wolf G, Ziyadeh FN, Schroeder R. et al. Angiotensin II inhibits inducible nitric oxide synthase in tubular MCT cells by a posttranscriptional mechanism. J Am Soc Nephrol 1997; 8: 551-7.
• 9 Pastore L, Tessitore A, Martinotti S. et al. Angiotensin II stimulates intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells and increases soluble ICAM-1 release in vivo. Circulation 1999; 100: 1646-52.
• 10 Tummala PE, Chen XL, Sundell CL. et al. Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature: A potential link between the renin-angiotensin system and atherosclerosis. Circulation 1999; 100: 1223-9.
• 11 Piqueras L, Kubes P, Alvarez A. et al. Angiotensin II induces leukocyte-endothelial cell interactions in vivo via AT(1) and AT(2) receptor-mediated P-selectin upregulation. Circulation 2000; 102: 2118-23.
• 12 Nishimura H, Tsuji H, Masuda H. et al. Angiotensin II increases plasminogen activator inhibitor-1 and tissue factor mRNA expression without changing that of tissue type plasminogen activator or tissue factor pathway inhibitor in cultured rat aortic endothelial cells. Thromb Haemost 1997; 77: 1189-95.
• 13 Nishimura H, Tsuji H, Masuda H. et al. The effects of angiotensin metabolites on the regulation of coagulation and fibrinolysis in cultured rat aortic endothelial cells. Thromb Haemost 1999; 82: 1516-21.
• 14 Larsson PT, Schwieler JH, Wallen NH. Platelet activation during angiotensin II infusion in healthy volunteers. Blood Coagul Fibrinolysis 2000; 11: 61-9.
• 15 van Leeuwen RT, Kol A, Andreotti F. et al. Angiotensin II increases plasminogen activator inhibitor type 1 and tissue-type plasminogen activator messenger RNA in cultured rat aortic smooth muscle cells. Circulation 1994; 90: 362-8.
• 16 Wilson HM, Haites NE, Booth NA. Effect of angiotensin II on plasminogen activator inhibitor-1 production by cultured human mesangial cells. Nephron 1997; 77: 197-204.
• 17 Ridker PM, Gaboury CL, Conlin PR. et al. Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II. Evidence of a potential interaction between the renin- angiotensin system and fibrinolytic function. Circulation 1993; 87: 1969-73.
• 18 Labinjoh C, Newby DE, Dawson P. et al. Fibrinolytic actions of intra-arterial angiotensin II and bradykinin in vivo in man. Cardiovasc Res 2000; 47: 707-14.
• 19 Larsson PT, Schwieler JH, Wallen NH. et al. Acute effects of angiotensin II on fibrinolysis in healthy volunteers. Blood Coagul Fibrinolysis 1999; 10: 19-24.
• 20 Poplawski A. The effect o angiotensin II on the platelet aggregation induced by adenosine diphosphate, epinephrine and thrombin. Experientia 1970; 26: 86
• 21 Ding YA, MacIntyre DE, Kenyon CJ. et al. Potentiation of adrenaline-induced platelet aggregation by angiotensin II. Thromb Haemost 1985; 54: 717-20.
• 22 Swartz SL, Moore TJ. Effect of angiotensin II on collagen-induced platelet activation in normotensive subjects. Thromb Haemost 1990; 63: 87-90.
• 23 Jagroop IA, Mikhailidis DP. Angiotensin II can induce and potentiate shape change in human platelets: effect of losartan. J Hum Hypertens 2000; 14: 581-5.
• 24 Rajagopalan S, Kurz S, Munzel T. et al. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 1996; 97: 1916-23.
• 25 Kerins DM, Hao Q, Vaughan DE. Angiotensin induction of PAI-1 expression in endothelial cells is mediated by the hexapeptide angiotensin IV. J Clin Invest 1995; 96: 2515-20.
• 26 Gesualdo L, Ranieri E, Monno R. et al. Angiotensin IV stimulates plasminogen activator inhibitor-1 expression in proximal tubular epithelial cells. Kidney Int 1999; 56: 461-70.
• 27 Hill-Kapturczak N, Kapturczak MH, Block ER. et al. Angiotensin II-stimulated nitric oxide release from porcine pulmonary endothelium is mediated by angiotensin IV. J Am Soc Nephrol 1999; 10: 481-91.
• 28 Huang WC, Ploth DW, Bell PD. et al. Bilateral renal function responses to converting enzyme inhibitor (SQ 20,881) in two-kidney, one clip Goldblatt hypertensive rats. Hypertension 1981; 3: 285-93.
• 29 Giles AR. Guidelines for the use of animals in biomedical research. Thromb Haemost 1987; 58: 1078-84.
• 30 Zatz R. A low cost tail-cuff method for the estimation of mean arterial pressure in conscious rats. Lab Anim Sci 1990; 40: 198-201.
• 31 Wilcox CS, Welch WJ. Thromboxane mediation of the pressor response to infused angiotensin II. Am J Hypertens 1990; 3: 242-9.
• 32 Matys T, Pawlak R, Kucharewicz I. et al. Hypotensive effect of angiotensin II after AT1-receptor blockade with losartan. J Physiol Pharmacol 2000; 51: 161-6.
• 33 Coleman JK, Lee I J, Miller JM. et al. Changes in cochlear blood flow due to intra-arterial infusions of angiotensin II (3–8) (angiotensin IV) in guinea pigs. Hear Res 1998; 119: 61-8.
• 34 Reyers I, de Gaetano G, Donati MB. Venostasis-induced thrombosis in rats is not influenced by circulating platelet or leukocyte number. Agents Actions 1989; 28: 137-41.
• 35 Bjornsson TD, Schneider DE, Berger Jr H. Aspirin acetylates fibrinogen and enhances fibrinolysis. Fibrinolytic effect is independent of changes in plasminogen activator levels. J Pharmacol Exp Ther 1989; 250: 154-61.
• 36 He S, Antovic A, Blomback M. A simple and rapid laboratory method for determination of haemostasis potential in plasma. II. Modifications for use in routine laboratories and research work. Thromb Res 2001; 103: 355-61.
• 37 Buczko W, Mogielnicki A, Kramkowski K. et al. Aspirin and the fibrinolytic response. Thromb Res 2003; 110: 331-4.
• 38 Spillert CR, Sun S, Miller MA. et al. Hypertensionrelated coronary thrombosis: prothrombic role of angiotensin II. J Natl Med Assoc 1994; 86: 686-8.
• 39 Castoldi G, di Gioia CR, Pieruzzi F. et al. Angiotensin II modulates calponin gene expression in rat vascular smooth muscle cells in vivo. J Hypertens 2001; 19: 2011-8.
• 40 Amiri F, Garcia R. Renal angiotensin II receptor regulation in two-kidney, one clip hypertensive rats: effect of ACE inhibition. Hypertension 1997; 30: 337-44.
• 41 Johnson AK, Mann JF, Rascher W. et al. Plasma angiotensin II concentrations and experimentally induced thirst. Am J Physiol 1981; 240: R229-34.
• 42 Chabielska E, Pawlak R, Wollny T. et al. Antithrombotic activity of losartan in two kidney, one clip hypertensive rats. A study on the mechanism of action. J Physiol Pharmacol 1999; 50: 99-109.
• 43 Kucharewicz I, Pawlak R, Matys T. et al. Antithrombotic effect of captopril and losartan is mediated by angiotensin-( 1–7). Hypertension 2002; 40: 774-9.
• 44 Shibasaki Y, Mori Y, Tsutumi Y. et al. Differential kinetics of circulating angiotensin IV and II after treatment with angiotensin II type 1 receptor antagonist and their plasma levels in patients with chronic renal failure. Clin Nephrol 1999; 51: 83-91.
• 45 de Gasparo M, Catt KJ, Inagami T. et al. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev 2000; 52: 415-72.
• 46 Thomas WG, Mendelsohn FA. Angiotensin receptors: form and function and distribution. Int J Biochem Cell Biol 2003; 35: 774-9.
• 47 Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991; 43: 109-42.
• 48 Kerins DM, Hao Q, Vaughan DE. Angiotensin induction of PAI-1 expression in endothelial cells is mediated by the hexapeptide angiotensin IV. J Clin Invest 1995; 96: 2515-20.
• 49 Schaub RG, Simmons CA, Koets MH. et al. Early events in the formation of a venous thrombus following local trauma and stasis. Lab Invest 1984; 51: 218-24.
• 50 Lottermoser K, Hertfelder HJ, Gohlke P. et al. Short-term effects of exogenous angiotensin II on plasma fibrinolytic balance in normal subjects. Clin Exp Hypertens 2004; 26: 13-26.