Alterations in the Vascular Actions of Insulin in the Pathogenesis of Insulin Resistance and Hypertension

  • Subodh Verma
  • John H. McNeill
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 498)

Abstract

Resistance to the metabolic effects of insulin (insulin resistance) and hyperinsulinemia have been suggested to contribute to a cluster of abnormalities including diabetes, hypertension, obesity, hyperlipidemia, atherosclerosis, coronary artery disease and polycystic ovary syndrome.1–5 One of our primary interests has been the role of insulin resistance and hyperinsulinemia in the pathogenesis of hypertension independent of obesity and diabetes. In a series of studies we have demonstrated that drugs that specifically improve insulin sensitivity (counter insulin resistance) and decrease plasma insulin levels both prevent and reverse hypertension in experimental models of high blood pressure (BP).3,4,6–12 These data lend credence to the notion that insulin resistance and hyperinsulinemia may play an important role in the final expression of high BP. Following these observations, we focussed our efforts towards elucidating the mechanisms through which insulin resistance and hyperinsulinemia lead to hypertension in these models. Our studies have focussed on the interaction of insulin with endothelium derived relaxing and contracting factors. A growing body of evidence suggests that insulin exerts direct effects on vascular tone through stimulation of endothelium derived nitric oxide (NO). This has led to the suggestion that changes in the actions of insulin (in states of insulin resistance) may be important in modulating the expression of both cardiovascular and metabolic endpoints. For example, resistance to the vasodilatory action of insulin (vascular insulin resistance) has been documented in the insulin resistant states of diabetes, obesity and hypertension.13–16 Vascular insulin resistance may sensitize/predispose the vasculature to the effects of pressors and lead to an increased vascular smooth muscle (VSM) tone and reactivity. As the vasodilatory actions of insulin contribute significantly to whole body glucose disposal, vasoconstriction (secondary to vascular insulin resistance) may play a role in the development and/or reinforcement of skeletal muscle/whole body insulin resistance. In this paper, we briefly discuss the relationship between insulin resistance and hypertension from a pharmacological and mechanistic standpoint. We then present some data from our laboratory that suggest that the vascular actions of insulin are altered in insulin resistant hypertensive rats and that these effects may antedate the development of high BP. For a general discussion of insulin resistance in cardiovascular regulation, the reader is referred to several comprehensive reviews.1,3,4,17

Keywords

Obesity Serotonin Vanadate Norepinephrine Fructose 

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Subodh Verma
    • 1
  • John H. McNeill
    • 2
  1. 1.The Division of Cardiology Faculty of MedicineUniversity of CalgaryCanada
  2. 2.The Division of Pharmacology and Toxicology Faculty of Pharmaceutical SciencesThe University of British ColumbiaCanada

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