Summary
Hypertension has a high prevalence among subjects with decreased insulin sensitivity and/or hyperinsulinemia. Furthermore, angiotensin II plays a pivotal role in the regulation of vascular tone and is known to induce hypertrophy and/or hyperplasia in vascular smooth muscle cells. In the present study, the effect of insulin on angiotensin II induced smooth muscle cell growth (Wistar-Kyoto rat) was investigated. Cell growth was assessed by the measurement of [3H]thymidine incorporation into cell DNA. Insulin in a concentration range of 1.7 × 10−10–1.7 × 10−6 M lacked any effect on cell DNA synthesis. However, insulin enhanced the angiotensin 11 induced DNA synthesis in a concentration-dependent manner. This effect was similar in cells with a weak and in cells with a marked response in DNA synthesis to stimulation with 100 nM angiotensin 11. In conclusion, insulin is able to enhance angiotensin 11 induced DNA synthesis and may therefore function as a growth cofactor in vascular smooth muscle cells.
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Abbreviations
- AngII:
-
angiotensin II
- EGF:
-
epidermal growth factor
- bFGF:
-
basic fibroblast growth factor
- PDGF-BB:
-
platelet-derived growth factor-BB
- VSMC:
-
vascular smooth muscle cells
References
Banskota NK, Taub R, Zellner K, King GL (1989) Insulin, insulin-like growth factor I and platelet-derived growth factor interact additively in the induction of the protooncogene c-myc and cellular proliferation in cultured bovine aortic smooth muscle cell. Molecular Endocrinology 3:1183–1190
Banskota NK, Taub R, Zellner K, Olsen P, Kin GL (1989) Characterisation of induction of protooncogene c-myc and cellular growth in human vascular smooth muscle cells by insulin and IGF-I. Diabetes 38:123–129
Berk BC, Brock TA, Webb C, Taubman MB, Atkinson WJ, Gimbrone MA Jr, Alexander WR (1985) Epidermal growth factor, a vascular smooth muscle mitogen, induces rat aortic contraction. J Clin Invest 75:1083–1086
Bornfeld KE, Gilöf RA, Wasteson A, Lake M, Skottner A, Arnqvist AJ (1991) Binding and biological effects of insulin, insulin-analogues and insulin-like growth factors in rat aortic smooth muscle cells. A comparison of maximal growth promoting activities. Diabetologia 34:307–313
Bradford M (1976) A rapid and sensitive method of the quantitation of microgram quantities of protein utilizing the principal of protein-dye binding. Anal Biochem 72:248–254
Campbell DJ (1986) Circulating and tissue angiotensin system. J Clin Invest 79:1–6
Champell-Boswell M, Robertson AL Jr (1981) Effects of angiotensin II and vasopressin on human smooth muscle cells in vitro. Exp Mol Pathol 35:265–276
Dzau VJ, Gibbons GH, Pratt RE (1991) Molecular mechanisms of vascular renin-angiotensin system in myointimal hyperplasia. Hypertension 18 [Suppl II]:II-100–105
Dzau VJ, Gibbons GH (1991) Endothelium and growth factors in vascular remodeling of hypertension. Hypertension 18 [Suppl III]: III-115–121
Ferrari P, Weidmann P (1990) Editorial review: insulin, insulin sensitivity and hypertension. J Hypertension 8:491–500
Geisterfer AAT, Peach MJ, Ownes G (1988) Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 62:749–756
Kifor I, Dzau VJ (1987) Endothelial renin-angiotensin pathway: evidence for intracellular synthesis and secretion of angiotensins. Circ Res 60:422–428
Lindner V, Reidy MA (1991) Proliferation of smooth muscle cells after vascular injury is inhibited by an antibody against basic fibroblast growth factor. Proc Natl Acad Sci USA 88:3739–3743
Marble A (1976) Late complications of diabetes: a continuing challenge. Diabetologia 12:193–199
Milton RC (1964) An extended table of critical values for the Mann-Whitney (Wilcoxon) two sample statistic. J Am Statist Assoc 59:925–934
Nemecek GM, Coughlin SR, Handley DH, Moskowitz M (1986) Stimulation of aortic smooth muscle cell mitogenesis by serotonin. Proc Natl Acad Sci USA 83:674–678
Pfeifle B, Ditschuneit HH, Ditschuneit H (1980) Insulin as a cellular growth regulator of rat arterial smooth muscle cells in vitro. Horm Metab Res 12:381–385
Pfeifle B, Ditschuneit H (1981) Effect of insulin on growth of cultured human arterial smooth muscle cells. Diabetologia 20:155–158
Pfeifle B, Boeder H, Ditschuneit H (1986) Interaction of receptors of insulin-like growth-factor I, platelet derived growth factor and fibroblast growth factor in rat aortic cells. Endocrinology 120:2251–2258
Ross RJ (1970) The smooth muscle cell II: growth of smooth muscle in culture and formation of elastic fiber. J Cell Biol 50:172–182
Ross R (1986) The pathogenesis of atherosclerosis: an update. N Engl J Med 314:488–497
Ross R (1992) Polypeptide growth factors and atherosclerosis. Trends Cardiovasc Med 1:277–282
Sachinidis A, Ko Y, Nettekoven W, Wieczorek AJ, Düsing R, Vetter H (1992) The effect of angiotensin II on DNA synthesis varies considerably in vascular smooth muscle cells from different Wistar-Kyoto rats. J Hypertens 10:1159–1164
Samani NJ, Swales JD, Jeffreys AJ, Morton DB, Naftilan AJ, Lindpaintner K, Ganten D, Brammar WJ (1989) DNA fingerprinting of spontaneously hypertensive and Wistar-Kyoto rats: implications for hypertension research. J Hypertension 7:809–816
Schwartz SM, Reidy MA (1987) Common mechanisms of proliferation of smooth muscle in atherosclerosis and hypertension. Hum Pathol 18:240–247
West KM (1970) Epidemiology of diabetes and vascular lesions. Elsevier, Amsterdam
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Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday
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Ko, Y., Sachinidis, A., Wieczorek, A. et al. Insulin enhances angiotensin II induced DNA synthesis in vascular smooth muscle cells of the rat. Clin Investig 71, 379–382 (1993). https://doi.org/10.1007/BF00186627
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DOI: https://doi.org/10.1007/BF00186627