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The Inter-Relationship between Insulin Resistance and Hypertension

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Summary

Insulin resistance and compensatory hyperinsulinaemia commonly occur in patients with untreated essential hypertension. The coexistence of insulin resistance and hypertension can be viewed as a cause-effect relationship (insulin resistance as a cause of hypertension or vice versa) or as a noncausal association. Insulin can increase blood pressure via several mechanisms: increased renal sodium reabsorption, activation of the sympathetic nervous system, alteration of transmembrane ion transport, and hypertrophy of resistance vessels. Conversely, hypertension can cause insulin resistance by altering the delivery of insulin and glucose to skeletal muscle cells, resulting in impaired glucose uptake. For example, hypertension can impair vasodilation of skeletal muscle as a result of vascular structural changes and rarefaction, and increased response to vasoconstrictor stimuli. Also, the prevalence of muscle type 2b fibres (fast twitch fibres) may contribute to the development of insulin resistance. The common pathogenetic mechanism for both insulin resistance and hypertension could be activation of the sympathetic nervous system. This results in vasoconstriction, and may contribute to the genesis of vascular structural changes and increase the number of fast twitch fibres.

Finally, hypertension and insulin resistance can be viewed as a noncausal association, according to the following hypotheses: 1) they may represent 2 independent consequences of the same metabolic disorder (intracellular free calcium accumulation), or 2) insulin resistance is a genetic marker and/or a pathogenetic mechanism of multiple metabolic abnormalities frequently associated with hypertension.

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References

  • Anderson EA, Balon TW, Hoffman RP, Sinkey CA, Mark AL. Insulin increases sympathetic activity but not blood pressure in borderline hypertensive humans. Abstract. Hypertension 19: 621–627, 1992a

    Article  PubMed  CAS  Google Scholar 

  • Anderson EA, Gudbjornsdottir S, Elam M, Sellgren J, Mark AL. Insulin causes vasoconstriction and increases arterial pressure in obese insulin resistant hypertensive humans. Abstract Hypertension 20: 409, 1992b

    Google Scholar 

  • Anderson EA, Hoffman RP, Balon TW, Sinkey CA, Mark AL. Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. Journal of Clinical Investigation 87: 2246–2252, 1991

    Article  PubMed  CAS  Google Scholar 

  • Andersson O, Sivertsson R, Sannerstedt R, Beckman M, Magnusson M, et al. Body fat and glucose tolerance in early blood pressure elevation: its relation to arteriolar hypertrophy Clinical Science 63: 395s–398s, 1982

    Google Scholar 

  • Baron AD, Brechtel G, Johnson A, Henry D. Insulin (I) decreases norepinephrine’s (NE) pressor effect in I but not I resistant man. Hypertension 20: 406–407, 1992

    Google Scholar 

  • Beretta-Piccoli C, Davies DL, Boddy K, Brown JJ, Cumming AMM, et al. Relation of arterial pressure with body sodium, body potassium and plasma potassium in essential hypertension. Clinical Science 63: 257–270, 1982

    PubMed  CAS  Google Scholar 

  • Berne C, Fagius J, Niklasson F. Sympathetic response to oral carbohydrate administration. Journal of Clinical Investigation 84: 1403–1409, 1989

    Article  PubMed  CAS  Google Scholar 

  • Bonen A, Tan MH, Watson-Wright WM. Insulin binding and glucose uptake differences in rodent skeletal muscles. Diabetes 30: 702–704, 1981

    Article  PubMed  CAS  Google Scholar 

  • Brands MW, Hildebrandt DA, Mizelle HL, Hall JE. Hypertension during chronic hyperinsulinemia in rats is not salt-sensitive. Hypertension 19 (Suppl. I): 183–189, 1992

    Google Scholar 

  • Buchanan TA, Sipos GF, Gadalah S, Yip K, Marsh DJ, et al. Glucose tolerance and insulin action in rats with renovascular hypertension. Hypertension 18: 341–347, 1991

    Article  PubMed  CAS  Google Scholar 

  • Byyny RL, LoVerde M, Lloyd S, Mitchell W, Draznin B. Cytosolic calcium and insulin resistance in elderly patients with essential hypertension. American Journal of Hypertension 5: 459–464, 1992

    PubMed  CAS  Google Scholar 

  • Catalano C, Winocour PH, Thomas TH, Walker M, Sum CF, et al. Erythrocyte sodium-lithium countertransport activity and total body insulin-mediated glucose disposal in normoalbu-minuric normotensive Type 1 (insulin-dependent) diabetic patients. Diabetologia 36: 52–56, 1993

    Article  PubMed  CAS  Google Scholar 

  • Daly PA, Landsberg L. Hypertension in obesity and NIDDM. Diabetes Care 14: 240–248, 1991

    Article  PubMed  CAS  Google Scholar 

  • De Fronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ. The effect of insulin on renal handing of sodium, potassium, calcium, and phosphate in man. Journal of Clinical Investigation 55: 845–855, 1975

    Article  Google Scholar 

  • Di Legge V, Benzi L, Lucarini AR, Ciccarone A, Lenzi M, et al. Insulin resistance and cardiovascular structural changes in essential hypertensives. Abstract American Journal of Hypertension 4: 121A, 1991

    Google Scholar 

  • Doria A, Fioretto P, Avogaro A, Carraro A, Morocutti A, et al. Insulin resistance is associated with high sodium-lithium countertransport in essential hypertension. American Journal of Physiology 261 (Endocrinology and Metabolism 24): E684–E691, 1991

    PubMed  CAS  Google Scholar 

  • Draznin B. Insulin resistance and cytosolic free calcium concentrations. Presented at 2nd European Nitrendipine Symposium: renal and metabolic considerations in hypertension, recent advances, pp. 18–19, Istanbul, October 15–18, 1992

  • Draznin B, Sussman KE, Eckel RH, Kao M, Yost T, et al. Possible role of cytosolic free calcium concentrations in mediating insulin resistance of obesity and hyperinsulinemia. Journal of Clinical Investigation 82: 1848–1852, 1988

    Article  PubMed  CAS  Google Scholar 

  • Ferrannini E. Metabolic abnormalities of hypertension. A lesson in complexity. Hypertension 18: 636–639, 1991

    Article  PubMed  CAS  Google Scholar 

  • Ferrannini E. The insulin resistance syndrome. Current Opinion in Nephrology and Hypertension 1: 291–298, 1992

    Article  PubMed  CAS  Google Scholar 

  • Ferrannini E. Insulin resistance syndrome Cardiovascular Risk Factors 3: 1, 1993

    Google Scholar 

  • Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, et al. Insulin resistance in essential hypertension. New England Journal of Medicine 317: 350–357, 1987

    Article  PubMed  CAS  Google Scholar 

  • Ferrari P, Weildmann P, Shaw S, Giachino D, Riesen W, et al. Altered insulin sensitivity, hyperinsulinemia, and dyslipidemia in individuals with a hypertensive parent. American Journal of Medicine 91: 589–593, 1991

    Article  PubMed  CAS  Google Scholar 

  • Folkow B. Structural factors: the vascular wall. Consequences of treatment. Hypertension 5 (Suppl. III): III/58–III/62, 1983

    Google Scholar 

  • Gans ROB, Toorn L, Bilo HJG, Nauta JJP, Heine RJ, et al. Renal and cardiovascular effects of exogenous insulin in healthy volunteers. Clinical Science 80: 219–225, 1991

    PubMed  CAS  Google Scholar 

  • Grassi G, Seravalle G, Gennari A, Bolla GB, Fatti L, et al. Obesità, insulino resistenza e sistema nervoso simpatico nell’uomo. XI Congresso Nazionale delia Società Italiana dell Tpertensione Arteriosa, Roma, 1–2 Ottobre, Abstract no. p 29, 1992

  • Haffner SM, Ferrannini E, Hazuda HP, Stern MP. Clustering of cardiovascular risk factors in confirmed prehypertensive individuals. Hypertension 20: 38–45, 1992

    Article  PubMed  CAS  Google Scholar 

  • Halkin H, Modan M, Shefi M, Almog S. Altered erythrocyte and plasma sodium and potassium in hypertension, a facet of hyperinsulinemia. Hypertension 11: 71–77, 1988

    Article  PubMed  CAS  Google Scholar 

  • Hall JE, Brands MW, Kivlighn SD, Mizelle HL, Hildebrandt DA, et al. Chronic hyperinsulinemia and blood pressure. Interaction with catecholamines? Hypertension 15: 519–527, 1990a

    Article  PubMed  CAS  Google Scholar 

  • Hall JE, Coleman TG, Mizelle HL, Smith MJ. Chronic hyperinsulinemia and blood pressure regulation. American Journal of Physiology 258 (Renal Fluid and Electrolyte Physiology 27): F722–F731, 1990b

    PubMed  CAS  Google Scholar 

  • Henrich HA, Romen W, Heimgartner E, Baumer F. Capillary rarefaction characteristic of the skeletal muscle of hypertensive patients. Klinische Wochenschrift 66: 54–60, 1988

    Article  PubMed  CAS  Google Scholar 

  • Huang WC, Hsieh PS, Jin JS. Chronic hyperinsulinemia causes hypertension in rats. Abstract no. 76, Journal of Hypertension 10 (Suppl. 4): 88, 1992

    Google Scholar 

  • Hunt SC, Wu LL, Hopkins PN, Williams RR. Elevated NA-Li countertransport and fasting insulin in patients with familial combined hyperlipidemia and hypertension. Abstract no 59, Hypertension 14: 345, 1989

    Google Scholar 

  • Hwang IS, Ho H, Hoffman BB, Reaven GM. Fructose-induced insulin resistance and hypertension in rats. Hypertension 10: 512–516, 1987

    Article  PubMed  CAS  Google Scholar 

  • James DE, Jenkins AB, Kraegen EW. Heterogeneity of insulin action in individual muscles in vivo: euglycemic clamp studies in rats. American Journal of Physiology 248 (Endocrinology and Metabolism 11): E567–E574, 1985

    PubMed  CAS  Google Scholar 

  • Juhlin-Dannfelt A, Frisk-Holmberg M, Karlsson J, Tesch P. Central and peripheral circulation in relation to muscle-fibre composition in normo- and hypertensive man. Clinical Science 56: 335–340, 1979

    PubMed  CAS  Google Scholar 

  • Julius S. Changing role of the autonomic nervous system in human hypertension. Journal of Hypertension 8 (Suppl.7): 59–65, 1990

    Google Scholar 

  • Julius S, Gudbrandsson T, Jamerson K, Andersson O. The interconnection between sympathetics, microcirculation and insulin resistance in hypertension. Blood Pressure 1: 9–19, 1992

    Article  PubMed  CAS  Google Scholar 

  • Julius S, Gudbrandsson T, Jamerson K, Shahab ST, Andersson O. The hemodynamic link between insulin resistance and hypertension. Journal of Hypertension 9: 983–986, 1991

    Article  PubMed  CAS  Google Scholar 

  • King GL, Kahn CR, Rechler MM, Nissley SP. Direct demonstration of separate receptors for growth and metabolic activities of insulin and multiplication-stimulating activity (an insulin like growth factor) using antibodies to the insulin receptor. Journal of Clinical Investigation 66: 130–140, 1980

    Article  PubMed  CAS  Google Scholar 

  • Krotkiewski M, Bylund-Fallenius AC, Holm J, Bjorntorp P, Grimby G, et al. Relationship between muscle morphology and metabolism in obese women: the effects of long-term physical training. European Journal of Clinical Investigation 13: 5–12, 1983

    Article  PubMed  CAS  Google Scholar 

  • Kuriyama S, Nakamura K, Horiguchi M, Uchida H, Sakai O. Decreased insulin-sensitive Ca2+ transport in cultured vascular smooth muscle cells from spontaneously hypertensive rats. American Journal of Hypertension 5: 892–895, 1992

    PubMed  CAS  Google Scholar 

  • Laakso M. The possible pathophysiology of insulin resistance syndrome. Cardiovascular Risk Factors 3: 55–66, 1993

    Google Scholar 

  • Laakso M, Edelman SV, Brechtel G, Baron AD. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. Journal of Clinical Investigation 85: 1844–1852, 1990

    Article  PubMed  CAS  Google Scholar 

  • Landin K, Tengborn L, Smith U. Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. Journal of Internal Medicine 229: 181–187, 1991

    Article  PubMed  CAS  Google Scholar 

  • Lembo G, Napoli R, Capaldo B, Rendina V, Iaccarino G, et al. Abnormal sympathetic overactivity evoked by insulin in the skeletal muscle of patients with essential hypertension. Journal of Clinical Investigation 90: 24–29, 1992a

    Article  PubMed  CAS  Google Scholar 

  • Lembo G, Napoli R, Rendina V, Capaldo B, Iaccarino G, et al. L’aumento del tono simpatico induce insulinoresistenza nel soggetto normale. IX Congresso Nazionale della Societa Italiana dell’Ipertensione Arteriosa, Roma, 1–2 Ottobre, 1992 p. 66, 1992b

    Google Scholar 

  • Lembo G, Rendina V, Lamenza F, Iaccarino G, Volpe M, et al. Insulin reduces forearm vasoconstriction evoked by reflex sympathetic activation in healthy humans. Abstract no 53 Hypertension 20: 409, 1992c

    Google Scholar 

  • Lillioja S, Young AA, Culter CL, Ivy JL, Abbott GH, et al. Skeletal muscle capillary density and fiber type as possible determinants of in vivo insulin resistance in man. Journal of Clinical Investigation 80: 415–424, 1987

    Article  PubMed  CAS  Google Scholar 

  • Lithell H. Insulin resistance and cardiovascular drugs. Clinical and Experimental Hypertension — Theory and Practice A14: 151–162, 1992

    Article  CAS  Google Scholar 

  • Mitrakou A, Mokan M, Bolli G, Veneman T, Jenssen T, et al. Evidence against the hypothesis that hyperinsulinemia increases sympathetic nervous system activity in man. Metabolism 41: 198–200, 1992

    Article  PubMed  CAS  Google Scholar 

  • Moore RD. Effects of insulin upon ion transport. Biochimica et Biophysica Acta 737: 1–49, 1983

    Article  PubMed  CAS  Google Scholar 

  • Morgan DA, Ray CA, Balon TW, Mark AL. Metformin increases insulin sensitivity and lowers arterial pressure in spontaneously hypertensive rats. Abstract no. P6 Hypertension 20: 421, 1992

    Google Scholar 

  • Mott DM, Clark RL, Andrews WJ, Foley JE. Insulin-resistant Na+ pump activity in adipocytes from obese humans. American Journal of Physiology 249 (Endocrinology and Metabolism 12): El 60–E164, 1985

    Google Scholar 

  • Natali A, Buzzigoli G, Taddei S, Santoro D, Cerri M, et al. Effects of insulin on hemodynamics and metabolism in human forearm. Diabetes 39: 490–500, 1990

    Article  PubMed  CAS  Google Scholar 

  • Natali A, Gal van Q, Santoro D, Taddei S, Salvetti A, et al. Relationship between insulin release, antinatriuresis, and hypo-kalemia following glucose ingestion in normal and hypertensive man. Clinical Science, in press, 1993

  • Natali A, Santoro D, Palombo C, Cerri M, Ghione S, et al. Impaired insulin action on skeletal muscle metabolism in essential hypertension. Hypertension 17: 170–178, 1991

    Article  PubMed  CAS  Google Scholar 

  • O’Hare JA, Minaker KL, Meneilly GS, Rowe JW, Pallotta JA, et al. Effect of insulin on plasma norepinephrine and 3,4-dihy-doxyphenylalanine in obese men. Metabolism 38: 322–329, 1989

    Article  PubMed  Google Scholar 

  • Pedrinelli R, Spessot M, Salvetti A. Reactive hyperemia during short-term blood flow and pressure changes in the hypertensive forearm. Journal of Hypertension 8: 467–471, 1990

    Article  PubMed  CAS  Google Scholar 

  • Pfeifle B, Ditschuneit H. Effect of insulin on growth of cultured human arterial smooth muscle cells. Diabetologia 20: 155–158, 1981

    Article  PubMed  CAS  Google Scholar 

  • Pollare T, Lithell H, Berne C. Insulin resistance is a characteristic feature of primary hypertension independent of obesity. Metabolism 39: 167–174, 1990

    Article  PubMed  CAS  Google Scholar 

  • Resnick LM. Calcium metabolism in hypertension and allied metabolic disorders. Diabetes Care 14: 505–520, 1991

    Article  PubMed  CAS  Google Scholar 

  • Reusch JEB, Begum N, Sussman KE, Draznin B. Regulation of GLUT-4 phosphorylation by intracellular calcium in adipocytes. Endocrinology 129: 3269–3273, 1991

    Article  PubMed  CAS  Google Scholar 

  • Rocchini AP, Katch V, Kveselis D, Moorehead C, Martin M, et al. Insulin and renal sodium retention in obese adolescents. Hypertension 14: 367–374, 1989a

    Article  PubMed  CAS  Google Scholar 

  • Rocchini AP, Key J, Bondie D, Chigo R, Moorehead C, et al. The effect of weight loss on the sensitivity of blood pressure to sodium in obese adolescents. New England Journal of Medicine 321: 580–585, 1989b

    Article  PubMed  CAS  Google Scholar 

  • Rocchini AP, Moorehead C, London M, Antishin K. Salt sensitivity and insulin resistance. Abstract. Circulation 82: 111–87, 1990

    Article  Google Scholar 

  • Rooney DP, Edgar JDM, Sheridan B, Atkinson AB, Bell PM. The effects of low dose insulin infusions on the renin angiotensin and sympathetic nervous systems in normal man. European Journal of Clinical Investigation 21: 430–435, 1991

    Article  PubMed  CAS  Google Scholar 

  • Rowe JW, Young JB, Minaker KL, Stevens AL, Pallotta J, et al. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes 30: 219–225, 1981

    PubMed  CAS  Google Scholar 

  • Saudek CD, Boulter PR, Knopp RH, Arky RA. Sodium retention accompanying insulin treatment of diabetes mellitus. Diabetes 23: 240–246, 1974

    PubMed  CAS  Google Scholar 

  • Schaefer W, PrieBen J, Mannhold R, Gries AF. Ca2+ -Mg2+ — ATPase activity of human red blood cells in healthy and diabetic volunteers. Klinische Wochenschrift 65: 17–21, 1987

    Article  PubMed  CAS  Google Scholar 

  • Segal S, Lloyd S, Sherman N, Sussman K, Draznin B. Postprandial changes in cytosolic free calcium and glucose uptake in adipocytes in obesity and non-insulin-dependent diabetes mellitus. Hormone Research 34: 39–44, 1990

    Article  PubMed  CAS  Google Scholar 

  • Shamiss A, Carroll J, Rosenthal T. Insulin resistance in secondary hypertension. American Journal of Hypertension 5: 26–28, 1992

    PubMed  CAS  Google Scholar 

  • Sharma AM, Ruland K, Spies KP, Distler A. Salt sensitivity in young normotensive subjects is associated with a hyperinsu-linemic response to oral glucose. Journal of Hypertension 9: 329–335, 1991

    Article  PubMed  CAS  Google Scholar 

  • Tedde R, Sechi LA, Marigliano A, Pala A, Scano L. Antihypertensive effect of insulin reduction in diabetic-hypertensive patients. American Journal of Hypertension 2: 163–170, 1989

    PubMed  CAS  Google Scholar 

  • Tomiyama H, Kushiro T, Abeta H, Kurumatani H, Taguchi H, et al. Blood pressure response to hyperinsulinemia in salt-sensitive and salt-resistant rats. Hypertension 20: 596–600, 1992

    Article  PubMed  CAS  Google Scholar 

  • Wolpert HA, Steen SN, Istfan NW, Simonson DC. Disparate effects of weight loss on insulin sensitivity and erythrocyte sodium-lithium countertransport activity. American Journal of Hypertension 5: 754–757, 1992

    PubMed  CAS  Google Scholar 

  • Zemel MB, Johnson BA, Ambrozy SA. Insulin-stimulated vascular relaxation. Role of Ca++ -ATPase. American Journal of Hypertension 5: 637–641, 1992

    PubMed  CAS  Google Scholar 

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  1. Cattedra di Medicina Interna, Clinica Medica I, University of Pisa, Pisa, Italy

    A. Salvetti, G. Brogi, V. Di Legge & G. P. Bernini

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  1. A. Salvetti
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  3. V. Di Legge
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Salvetti, A., Brogi, G., Di Legge, V. et al. The Inter-Relationship between Insulin Resistance and Hypertension. Drugs 46 (Suppl 2), 149–159 (1993). https://doi.org/10.2165/00003495-199300462-00024

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