Role of kinins and nitric oxide in the effects of angiotensin converting enzyme inhibitors on neointima formation

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Circulation Research. 1993;72:1202-1210

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ARTICLES

Role of kinins and nitric oxide in the effects of angiotensin converting enzyme inhibitors on neointima formation

RD Farhy, OA Carretero, KL Ho and AG Scicli
Hypertension and Vascular Research Division, Ford Hospital, Detroit, MI 48202.

Marked neointima formation occurs after balloon injury to the intima of rat arteries. Angiotensin II has been implicated as a growth factor in this process, since angiotensin converting enzyme (ACE) inhibitors block neointima formation after injury. However, ACE is an important kininase, and its inhibitors may act in part by a kinin-mediated mechanism. Kinins are also known to stimulate synthesis of endothelium- derived relaxing factor/nitric oxide (EDRF/NO) and prostacyclin, both of which have antigrowth effects. To determine whether the effect of ACE inhibitors on neointima formation is due to blockade of angiotensin II synthesis alone and/or inhibition of kinin inactivation, we followed two approaches. First, we compared the inhibition of neointima formation induced by the AT1-type angiotensin II receptor antagonist losartan with that caused by the ACE inhibitor ramipril. We also studied whether a kinin receptor antagonist, Hoe 140, blocks the effect of two different ACE inhibitors, ramipril and enalapril, on neointima formation. In addition, we studied whether the effect of ramipril is blocked by an NO synthesis inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME). Although both ramipril and losartan significantly reduced neointima formation, ramipril had a more marked effect (p < 0.05 for ramipril versus losartan). The kinin antagonist Hoe 140 reduced the inhibitory effect of ramipril and enalapril by 73% and 62%, respectively. The remaining effect of the ACE inhibitors was now similar to that of losartan. Inhibition of neointima formation by ramipril was also blocked by the NO synthesis inhibitor L- NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

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				J. Chao and L. Chao Kallikrein-kinin in stroke, cardiovascular and renal disease Exp Physiol, May 1, 2005; 90(3): 291 - 298. [Abstract] [Full Text] [PDF]

				H. M. Dourron, G. M. Jacobson, J. L. Park, J. Liu, D. J. Reddy, M. L. Scheel, and P. J. Pagano Perivascular gene transfer of NADPH oxidase inhibitor suppresses angioplasty-induced neointimal proliferation of rat carotid artery Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H946 - H953. [Abstract] [Full Text] [PDF]

				A. C. Scott, R. Wensel, C. H. Davos, P. Georgiadou, L. Ceri Davies, A. J.S. Coats, D. P. Francis, and M. F. Piepoli Putative contribution of prostaglandin and bradykinin to muscle reflex hyperactivity in patients on Ace-inhibitor therapy for chronic heart failure Eur. Heart J., October 2, 2004; 25(20): 1806 - 1813. [Abstract] [Full Text] [PDF]

				D. Yavuz, M. Koc, A. Toprak, I. Akp{iota}nar, A. Velioglu, O. Deyneli, G. Haklar, and S. Akalln Effects of ACE inhibition and AT1-receptor antagonism on endothelial function and insulin sensitivity in essential hypertensive patients Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 197 - 203. [Abstract] [PDF]

				W.J. Remme Reconsider the management of all coronary artery disease patients: Importance of the EUROPA trial Eur. Heart J. Suppl., July 1, 2003; 5(suppl_E): E23 - E30. [Abstract] [PDF]

				B. M. Singh and J. L. Mehta Interactions Between the Renin-Angiotensin System and Dyslipidemia: Relevance in the Therapy of Hypertension and Coronary Heart Disease Arch Intern Med, June 9, 2003; 163(11): 1296 - 1304. [Abstract] [Full Text] [PDF]

				G. M. Jacobson, H. M. Dourron, J. Liu, O. A. Carretero, D. J. Reddy, T. Andrzejewski, and P. J. Pagano Novel NAD(P)H Oxidase Inhibitor Suppresses Angioplasty-Induced Superoxide and Neointimal Hyperplasia of Rat Carotid Artery Circ. Res., April 4, 2003; 92(6): 637 - 643. [Abstract] [Full Text] [PDF]

				Y. Zhang, D. Carreras, and A. J. de Bold Discoordinate re-expression of cardiac fetal genes in N{omega}-nitro-L-arginine methyl ester (L-NAME) hypertension Cardiovasc Res, January 1, 2003; 57(1): 158 - 167. [Abstract] [Full Text] [PDF]

				F. E. Rey and P. J. Pagano The Reactive Adventitia: Fibroblast Oxidase in Vascular Function Arterioscler Thromb Vasc Biol, December 1, 2002; 22(12): 1962 - 1971. [Abstract] [Full Text] [PDF]

				S. Kim, Y. Izumi, Y. Izumiya, Y. Zhan, M. Taniguchi, and H. Iwao Beneficial Effects of Combined Blockade of ACE and AT1 Receptor on Intimal Hyperplasia in Balloon-Injured Rat Artery Arterioscler Thromb Vasc Biol, August 1, 2002; 22(8): 1299 - 1304. [Abstract] [Full Text] [PDF]

				N. Uhlenius, O. Vuolteenaho, and I. Tikkanen Renin-angiotensin blockade improves renal cGMP production via non-AT2-receptor mediated mechanisms in hypertension-induced by chronic NOS inhibition in rat Journal of Renin-Angiotensin-Aldosterone System, December 1, 2001; 2(4): 233 - 239. [Abstract] [PDF]

				L. Yau, D. P. Wilson, J. P. Werner, and P. Zahradka Bradykinin receptor antagonists attenuate neointimal proliferation postangioplasty Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1648 - H1656. [Abstract] [Full Text] [PDF]

				E. Kintsurashvili, I. Duka, I. Gavras, C. Johns, D. Farmakiotis, and H. Gavras Effects of ANG II on bradykinin receptor gene expression in cardiomyocytes and vascular smooth muscle cells Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1778 - H1783. [Abstract] [Full Text] [PDF]

				M. Katoh, K. Egashira, C. Kataoka, M. Usui, M. Koyanagi, S. Kitamoto, Y. Ohmachi, A. Takeshita, and H. Narita Regression by ACE inhibition of arteriosclerotic changes induced by chronic blockade of NO synthesis in rats Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2306 - H2312. [Abstract] [Full Text] [PDF]

				S. Kim, Y. Zhan, Y. Izumi, H. Yasumoto, M. Yano, and H. Iwao In Vivo Activation of Rat Aortic Platelet-Derived Growth Factor and Epidermal Growth Factor Receptors by Angiotensin II and Hypertension Arterioscler Thromb Vasc Biol, December 1, 2000; 20(12): 2539 - 2545. [Abstract] [Full Text] [PDF]

				J. Agata, R. Q. Miao, K. Yayama, L. Chao, and J. Chao Bradykinin B1 Receptor Mediates Inhibition of Neointima Formation in Rat Artery After Balloon Angioplasty Hypertension, September 1, 2000; 36(3): 364 - 370. [Abstract] [Full Text] [PDF]

				C. Emanueli, M. B. Salis, J. Chao, L. Chao, J. Agata, K.-F. Lin, A. Munao, S. Straino, A. Minasi, M. C. Capogrossi, et al. Adenovirus-Mediated Human Tissue Kallikrein Gene Delivery Inhibits Neointima Formation Induced by Interruption of Blood Flow in Mice Arterioscler Thromb Vasc Biol, June 1, 2000; 20(6): 1459 - 1466. [Abstract] [Full Text] [PDF]

				B.-S. Tea, S. Der Sarkissian, R. M. Touyz, P. Hamet, and D. deBlois Proapoptotic and Growth-Inhibitory Role of Angiotensin II Type 2 Receptor in Vascular Smooth Muscle Cells of Spontaneously Hypertensive Rats In Vivo Hypertension, May 1, 2000; 35(5): 1069 - 1073. [Abstract] [Full Text] [PDF]

				M. KASHIWAGI, M. SHINOZAKI, H. HIRAKATA, K. TAMAKI, T. HIRANO, M. TOKUMOTO, H. GOTO, S. OKUDA, and M. FUJISHIMA Locally Activated Renin-Angiotensin System Associated with TGF-{beta}1 as a Major Factor for Renal Injury Induced by Chronic Inhibition of Nitric Oxide Synthase in Rats J. Am. Soc. Nephrol., April 1, 2000; 11(4): 616 - 624. [Abstract] [Full Text] [PDF]

				A. M. Holm, C. B. Andersen, S. Haunso, and P. Riis Hansen ACE-inhibition promotes apoptosis after balloon injury of rat carotid arteries Cardiovasc Res, February 1, 2000; 45(3): 777 - 782. [Abstract] [Full Text] [PDF]

				T. J. Anderson, E. Elstein, H. Haber, and F. Charbonneau Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study) J. Am. Coll. Cardiol., January 1, 2000; 35(1): 60 - 66. [Abstract] [Full Text] [PDF]

				T. J. Anderson Assessment and treatment of endothelial dysfunction in humans J. Am. Coll. Cardiol., September 1, 1999; 34(3): 631 - 638. [Full Text] [PDF]

				H. Murakami, K. Yayama, R. Q. Miao, C. Wang, L. Chao, and J. Chao Kallikrein Gene Delivery Inhibits Vascular Smooth Muscle Cell Growth and Neointima Formation in the Rat Artery After Balloon Angioplasty Hypertension, August 1, 1999; 34(2): 164 - 170. [Abstract] [Full Text] [PDF]

				D. P. Wilson, L. Saward, P. Zahradka, and P. Kee Cheung Angiotensin II receptor antagonists prevent neointimal proliferation in a porcine coronary artery organ culture model Cardiovasc Res, June 1, 1999; 42(3): 761 - 772. [Abstract] [Full Text] [PDF]

				A. Warnholtz, G. Nickenig, E. Schulz, R. Macharzina, J. H. Brasen, M. Skatchkov, T. Heitzer, J. P. Stasch, K. K. Griendling, D. G. Harrison, et al. Increased NADH-Oxidase�Mediated Superoxide Production in the Early Stages of Atherosclerosis : Evidence for Involvement of the Renin-Angiotensin System Circulation, April 20, 1999; 99(15): 2027 - 2033. [Abstract] [Full Text] [PDF]

				H. G Hutchinson, L. Hein, M. Fujinaga, and R. E Pratt Modulation of vascular development and injury by angiotensin II Cardiovasc Res, March 1, 1999; 41(3): 689 - 700. [Abstract] [Full Text] [PDF]

				S. Brodsky, K. Gurbanov, Z. Abassi, A. Hoffman, R. R. Ruffolo Jr, G. Z. Feuerstein, and J. Winaver Effects of Eprosartan on Renal Function and Cardiac Hypertrophy in Rats With Experimental Heart Failure Hypertension, October 1, 1998; 32(4): 746 - 752. [Abstract] [Full Text] [PDF]