Abstract
The involvement of the circulating and local renin-angiotensin system in atherosclerotic process has been hypothesized on the basis of experimental data showing presence and specific actions of the components of this system in the vascular wall. In particular, angiotensin II may participate in well known events in atherogenesis as the control of smooth muscle cell growth and proliferation.
Recent studies have shown an effect of angiotensin converting enzyme (ACE) inhibition on the development of atherosclerosis in animal models. Captopril and cilazapril prevent myointimal proliferation after vascular injury in rat. Captopril reduces aortic cholesterol content and percentage intmal aortic surface covered by lesions in Watanabe heritable hyperlipidemic rabbits. Captopril also significantly reduces the progression of carotid and coronary lesions in monkeys fed a high cholesterol diet. In addition, a role for converting enzyme inhibitors in reducing aortic and microvascular growth either in hypertensive or normotensive rats has been demonstrated. It is possible that ACE-inhibitors prevent angiotensin II-induced vascular proliferation and thereby suppress the development of atherosclerosis in animals. It is also conceivable that the blood pressure effects of ACE-inhibitors could play a role in the antiatherosclerotic effect shown by these drugs, even though this explanation cannot be addressed by studies dealing with normotensive animals. Then, other mechanisms could be involved, including hypothesized effects of blockade of the renin-angiotensin system on sympathetic nervous system activity, regulation of vascular growth factors and insulin sensivity.
The clinical significance of these experimental findings is unknown. Molecular mechanisms by which the renin-angiotensin system can act on atherosclerosis pathogenesis and the influence of ACE-inhibitors on the course of arterial diseases in humans ought to be important subjects of future investigations.
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References
AbergG. andFerrerP. (1990): Effects of captopril on atherosclerosis in cynomolgus monkeys -J. Cardiovasc. Pharmacol.15 (Suppl. 5): S65-S72.
CampbellD.J. (1987): Circulating and tissue angiotensin systems - J. Clin. Invest.79: 1–6.
Campbell-BoswellM. andRobertsonA.L. (1981): Effects of angiotensis 11 and vasopressin on human smooth muscle cellsin vitro - Exp. Mol. Pathol.35: 265–276.
CassisL.A.,SayeJ.A. andPeachM.J. (1988): Location and regulation of rat angiotensinogen messenger RNA - Hypertension11: 591–596.
ChobanianA. V.,HaudenschildC. C.,NickersonC. andDragoR. (1990): Antiatherogenic effect of captopril in the Watanabe heritable hyperlipidemic rabbit -Hypertension15: 327–331.
DzauV.J. (1988): Circulating versus local renin-angiotensin system in cardiovascular homeostasis -Circulation77 (Suppl. 1): I4-I13.
DzauV.J. (1987): Vascular angiotensin pathways: a new therapeutic target - J. Cardiovasc. Pharmacol.10 (Suppl. 7): S9-S16.
DzauV.J. andPrattR.E. (1986): Renin-angiotensin system: biology, physiology and pharmacology. In Haber E., Morgan H., Katz A. and Fozzard H. Handbook of experimental cardiology - Raven Press -New York 1631–1661.
FeranndezL.A.,TwicklerJ. andMeadA. (1985): Neovascularization produced by angiotensin II - J. Lab. Clin. Med.105: 141–145.
HaudenschildC. C. andChobanianA. Y. (1984): Blood pressure lowering diminishes age-related changes in the rat aortic intima - Hypertension6 (Suppl. I): 162–168.
JacksonT.R.,BlairL.A.C.,MarshallJ.,GoedertM. andHanleyM.R. (1988): The mas oncogene encodes an angiotensin receptor - Nature335: 437–440.
KannelW.B. andSorlieP. (1975): Hypertension in Framingham. In: Paul O. Epidemiology and control of hypertension. Stratton Intercontinental Medical Books - New York 553–590.
KawaharaY.,SunakoM.,TsudaT.,FukuzakiH.,FukumotoY. andTakaiY. (1988): Angiotensin II induces expression of the c-fos gene through protein kinase C activation and calcium ion mobilization in cultured vascular smooth muscle cells - Biochem. Biophys. Res. Commun.150: 52–59.
LeverA.F. (1986): Slow pressor mechanisms in hypertension: a role for hypertrophy of resistance vessels? - J. Hypertension4: 515–524.
LichtensteinA.H.,DragoR.,NickersonC.,PrescotM.F.,LeeS. Q. andChobanianA. V. (1989): The effect of propranolol on atherogenesis in the Watanabe heritable hyperlipidemic rabbit - J. Vasc. Med. Biol. 1: 248–254.
LithellH.O.,PollareT. andBerneC. (1990): Insulin sensitivity in newly detected hypertensive patients: influence of captopril and other antihypertensive agents on insulin sensitivity and related biological parameters - J. Cardiovasc. Pharmacol.15 (Suppl. 5): S46-S52.
MullerR.,BrovoR.,BurckhardtJ. andCurranT. (1984): Induction of c-fos gene and protein by growth factors precedes activation of c-myc - Nature312: 716–720.
NaftilanA.J.,PrattR.E. andDzauV.J. (1989): Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells - J. Clin. Invest.83: 1419–1424.
NakamuraY.,NakamuraK.,MatsukuraT. andNakamuraK. (1988): Vascular angiotensin converting enzyme activity in spontaneously hypertensive rats and its inhibition with cilazapril - J. Hypertension6: 105–110.
OverturfM.L.,SybersH.D. andSmithS.A. (1985): Captopril-induced hyperreninemia in cholesterol-fed rabbits - Res. Commun. Chem. Pathol. Pharmacol.47: 229–253.
OwenN.E. andVillerealM.L. (1983): Lys-bradykinin stimulates Na+ influx and DNA synthesis in cultured human fibroblasts - Cell.32: 979–985.
OwensG.K. (1987): Influence of blood pressure on development of aortic medial smooth muscle hypertrophy in spontaneously hypertensive rats -Hypertension9: 178–187.
PollareT.,LithellH.O. andBerneC (1989): A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patient with hypertension - N. Engl. J. Med.321: 868–873.
PowellJ.S.,ClozelJ.P.,MullerR.K.M.,KuhnH.,HeftiF.,HosangM. andBaumgartnerH.R. (1989): Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury -Science245: 186–188.
RossR.,GlomsetJ.,KariyaB. andHarkerL. (1974): A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro -Proc. Natl. Acad. Sci. USA71: 1207–1210.
TangS.S.,StevensonL. andDzauV.J. (1990): Endothelial renin-angiotensin patway - Circ. Res.66: 103–108.
TiltonG.D.,BujaL.M.,BilheimerD. W.,ApprillP.,AshtonJ.,Mc NattJ.,KitaT. andWillersonJ.T. (1985): Failure of a slow channel calcium antagonist, verapamil, to retard atherosclerosis in the Watanabe heritable hyperlipidemic rabbit: an animal model of familial hypercholesterolemia - J. Am. Coll. Cardiol.6: 141–144.
UngerT. andGohlkeP. (1990): Tissue renin-angiotensin systems in the heart and vasculature: possible involvement in the cardiovascular actions of converting enzyme inhibitors - Am. J. Cardiol.65: 31–101.
VanNiekerkJ.L.M.,HendriksT.H.,DeBoerH.H.M. andVan't LaarA. (1984): Does nifedipine suppress atherogenesis in WHHL rabbits? - Atherosclerosis53: 91–98.
WangD.H. andPrewittR.L. (1990): Captopril reduces aortic and microvascular growth in hypertensive and normotensive rats - Hypertension15: 68–77.
WeinstockJ. V. (1986): The significance of angiotensin I converting enzyme in granulomatous inflammation. Functions of ACE in granulomas -Sarcoidosis3: 19–26.
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Ambrosioni, E., Bacchelli, S., Degli Esposti, D. et al. ACE-inhibitors and atherosclerosis. Eur J Epidemiol 8 (Suppl 1), 129–133 (1992). https://doi.org/10.1007/BF00145364
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DOI: https://doi.org/10.1007/BF00145364