(Circulation. 1999;99:896-902.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Microvascular Function Relates to Insulin Sensitivity and Blood Pressure in Normal Subjects
From the Department of Medicine (E.H.S., C.D.A.S., J.C.T.M, P.M.T.W, A.J.M.D, R.O.B.G.) and Department of Surgery (J.A.R.), Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands; and Institute for Cardiovascular Research-Vrije Universiteit (E.H.S., C.D.A.S., J.C.T.M., P.M.T.W., J.A.R., A.J.M.D., R.O.B.G.) Amsterdam, The Netherlands.
Correspondence to Dr Coen D.A. Stehouwer, Department of Medicine, Academic Hospital Vrije Universiteit, De Boelelaan 1117, 1007 MB, Amsterdam, The Netherlands. E-mail CDA.Stehouwer{at}AZVU.NL
Background—A strong but presently unexplained inverse association between blood pressure and insulin sensitivity has been reported. Microvascular vasodilator capacity may be a common antecedent linking insulin sensitivity to blood pressure. To test this hypothesis, we studied 18 normotensive and glucose-tolerant subjects showing a wide range in insulin sensitivity as assessed with the hyperinsulinemic, euglycemic clamp technique.
Methods and Results—Blood pressure was measured by 24-hour ambulatory blood pressure monitoring. Videomicroscopy was used to measure skin capillary density and capillary recruitment after arterial occlusion. Skin blood flow responses after iontophoresis of acetylcholine and sodium nitroprusside were evaluated by laser Doppler flowmetry. Insulin sensitivity correlated with 24-hour systolic blood pressure (24-hour SBP; r=-0.50, P<0.05). Capillary recruitment and acetylcholine-mediated vasodilatation were strongly and positively related to insulin sensitivity (r=0.84, P<0.001; r=0.78, P<0.001, respectively), and capillary recruitment was inversely related to 24-hour SBP (r=-0.53, P<0.05). Waist-to-hip ratio showed strong associations with insulin sensitivity, blood pressure, and the measures of microvascular function but did not confound the associations between these variables. Subsequent regression analysis showed that the association between insulin sensitivity and blood pressure was not independent of the estimates of microvascular function, and part of the variation in both blood pressure (R2=38%) and insulin sensitivity (R2=71%) could be explained by microvascular function.
Conclusions—Insulin sensitivity and blood pressure are associated well within the physiological range. Microvascular function strongly relates to both, consistent with a central role in linking these variables.
Key Words: hypertension • insulin • microcirculation • capillaries • endothelium
This article has been cited by other articles:
 |
|
 |
|
  A. R. Pries, H. Habazettl, G. Ambrosio, P. R. Hansen, J. C. Kaski, V. Schachinger, H. Tillmanns, G. Vassalli, I. Tritto, M. Weis, et al. A review of methods for assessment of coronary microvascular disease in both clinical and experimental settings Cardiovasc Res, June 25, 2008; (2008) cvn136v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Malik, V. Kondragunta, and I. J. Kullo Forearm Vascular Reactivity and Arterial Stiffness in Asymptomatic Adults From the Community Hypertension, June 1, 2008; 51(6): 1512 - 1518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-J. Mourad, G. des Guetz, H. Debbabi, and B. I. Levy Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation Ann. Onc., May 1, 2008; 19(5): 927 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cheng, C. Daskalakis, and B. Falkner Original Research: Capillary rarefaction in treated and untreated hypertensive subjects Therapeutic Advances in Cardiovascular Disease, April 1, 2008; 2(2): 79 - 88. [Abstract] [PDF]
|
|
|
|
 |
|
 L. A. Lesniewski, A. J. Donato, B. J. Behnke, C. R. Woodman, M. H. Laughlin, C. A. Ray, and M. D. Delp Decreased NO signaling leads to enhanced vasoconstrictor responsiveness in skeletal muscle arterioles of the ZDF rat prior to overt diabetes and hypertension Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1840 - H1850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. de Boer, R. G. IJzerman, R. T. de Jongh, E. C. Eringa, C. D.A. Stehouwer, Y. M. Smulders, and E. H. Serne Birth Weight Relates to Salt Sensitivity of Blood Pressure in Healthy Adults Hypertension, April 1, 2008; 51(4): 928 - 932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Eringa, C. D. A. Stehouwer, M. H. Roos, N. Westerhof, and P. Sipkema Selective resistance to vasoactive effects of insulin in muscle resistance arteries of obese Zucker (fa/fa) rats Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1134 - E1139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Okin, R. B. Devereux, K. E. Harris, S. Jern, S. E. Kjeldsen, L. H. Lindholm, B. Dahlof, and for the LIFE Study Investigators In-Treatment Resolution or Absence of Electrocardiographic Left Ventricular Hypertrophy Is Associated With Decreased Incidence of New-Onset Diabetes Mellitus in Hypertensive Patients: The Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study Hypertension, November 1, 2007; 50(5): 984 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Schillaci, M. Pirro, and E. Mannarino Left Ventricular Hypertrophy Reversal and Prevention of Diabetes: Two Birds With One Stone? Hypertension, November 1, 2007; 50(5): 851 - 853. [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Jonk, A. J. H. M. Houben, R. T. de Jongh, E. H. Serne, N. C. Schaper, and C. D. A. Stehouwer Microvascular Dysfunction in Obesity: A Potential Mechanism in the Pathogenesis of Obesity-Associated Insulin Resistance and Hypertension Physiology, August 1, 2007; 22(4): 252 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H. Serne, R. T. de Jongh, E. C. Eringa, R. G. IJzerman, and C. D.A. Stehouwer Microvascular Dysfunction: A Potential Pathophysiological Role in the Metabolic Syndrome Hypertension, July 1, 2007; 50(1): 204 - 211. [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Eringa, C. D. A. Stehouwer, K. Walburg, A. D. Clark, G. P. van Nieuw Amerongen, N. Westerhof, and P. Sipkema Physiological Concentrations of Insulin Induce Endothelin-Dependent Vasoconstriction of Skeletal Muscle Resistance Arteries in the Presence of Tumor Necrosis Factor-{alpha} Dependence on c-Jun N-Terminal Kinase Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 274 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Mitchell, J. A. Vita, M. G. Larson, H. Parise, M. J. Keyes, E. Warner, R. S. Vasan, D. Levy, and E. J. Benjamin Cross-Sectional Relations of Peripheral Microvascular Function, Cardiovascular Disease Risk Factors, and Aortic Stiffness: The Framingham Heart Study Circulation, December 13, 2005; 112(24): 3722 - 3728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mather and S. Verma Function determines structure in the vasculature: lessons from insulin resistance Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2005; 289(2): R305 - R306. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Blaauw, R. Graaff, M. G. van Pampus, J. J. van Doormaal, A. J. Smit, G. Rakhorst, and J. G. Aarnoudse Abnormal Endothelium-Dependent Microvascular Reactivity in Recently Preeclamptic Women Obstet. Gynecol., March 1, 2005; 105(3): 626 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M.R. Gill, A. Al-Mamari, W. R. Ferrell, S. J. Cleland, C. J. Packard, N. Sattar, J. R. Petrie, and M. J. Caslake Effects of prior moderate exercise on postprandial metabolism and vascular function in lean and centrally obese men J. Am. Coll. Cardiol., December 21, 2004; 44(12): 2375 - 2382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Jadhav, J Petrie, W Ferrell, S Cobbe, and N Sattar Insulin resistance as a contributor to myocardial ischaemia independent of obstructive coronary atheroma: a role for insulin sensitisation? Heart, December 1, 2004; 90(12): 1379 - 1383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Stewart, A. Kohen, D. Brouder, F. Rahim, S. Adler, R. Garrick, and M. S. Goligorsky Noninvasive interrogation of microvasculature for signs of endothelial dysfunction in patients with chronic renal failure Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2687 - H2696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. T. de Jongh, E. H. Serne, R. G. IJzerman, G. de Vries, and C. D.A. Stehouwer Free Fatty Acid Levels Modulate Microvascular Function: Relevance for Obesity-Associated Insulin Resistance, Hypertension, and Microangiopathy Diabetes, November 1, 2004; 53(11): 2873 - 2882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Eringa, C. D. A. Stehouwer, G. P. van Nieuw Amerongen, L. Ouwehand, N. Westerhof, and P. Sipkema Vasoconstrictor effects of insulin in skeletal muscle arterioles are mediated by ERK1/2 activation in endothelium Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2043 - H2048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Y. Wong, B. B. Duncan, S. H. Golden, R. Klein, D. J. Couper, B. E. K. Klein, L. D. Hubbard, A. R. Sharrett, and M. I. Schmidt Associations between the Metabolic Syndrome and Retinal Microvascular Signs: The Atherosclerosis Risk in Communities Study Invest. Ophthalmol. Vis. Sci., September 1, 2004; 45(9): 2949 - 2954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F. Mitchell, H. Parise, J. A. Vita, M. G. Larson, E. Warner, J. F. Keaney Jr, M. J. Keyes, D. Levy, R. S. Vasan, and E. J. Benjamin Local Shear Stress and Brachial Artery Flow-Mediated Dilation: The Framingham Heart Study Hypertension, August 1, 2004; 44(2): 134 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. de Jongh, E. H. Serne, R. G. IJzerman, G. de Vries, and C. D.A. Stehouwer Impaired Microvascular Function in Obesity: Implications for Obesity-Associated Microangiopathy, Hypertension, and Insulin Resistance Circulation, June 1, 2004; 109(21): 2529 - 2535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Meigs, F. B. Hu, N. Rifai, and J. E. Manson Biomarkers of Endothelial Dysfunction and Risk of Type 2 Diabetes Mellitus JAMA, April 28, 2004; 291(16): 1978 - 1986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. A. Stehouwer Endothelial dysfunction in diabetic nephropathy: state of the art and potential significance for non-diabetic renal disease Nephrol. Dial. Transplant., April 1, 2004; 19(4): 778 - 781. [Full Text] [PDF]
|
|
|
|
|
|
T F T Antonios, F M Rattray, D R J Singer, N D Markandu, P S Mortimer, and G A MacGregor Rarefaction of skin capillaries in normotensive offspring of individuals with essential hypertension Heart, February 1, 2003; 89(2): 175 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Clark, M. G. Wallis, E. J. Barrett, M. A. Vincent, S. M. Richards, L. H. Clerk, and S. Rattigan Blood flow and muscle metabolism: a focus on insulin action Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E241 - E258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Eringa, C. D.A. Stehouwer, T. Merlijn, N. Westerhof, and P. Sipkema Physiological concentrations of insulin induce endothelin-mediated vasoconstriction during inhibition of NOS or PI3-kinase in skeletal muscle arterioles Cardiovasc Res, December 1, 2002; 56(3): 464 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H Serne, R. G Ijzerman, R. T de Jongh, and C. D.A Stehouwer Blood pressure and insulin resistance: role for microvascular function?: [Cardiovasc Res 2002;53:271-276] Cardiovasc Res, August 1, 2002; 55(2): 418 - 419. [Full Text] [PDF]
|
|
|
|
|
|
E. H. Serne, R. G. IJzerman, R. O.B. Gans, R. Nijveldt, G. de Vries, R. Evertz, A. J.M. Donker, and C. D.A. Stehouwer Direct Evidence for Insulin-Induced Capillary Recruitment in Skin of Healthy Subjects During Physiological Hyperinsulinemia Diabetes, May 1, 2002; 51(5): 1515 - 1522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.J Irving, B.R Walker, J.P Noon, G.C.M Watt, D.J Webb, and A.C Shore Microvascular correlates of blood pressure, plasma glucose, and insulin resistance in health Cardiovasc Res, January 1, 2002; 53(1): 271 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Meigs, P. F. Jacques, J. Selhub, D. E. Singer, D. M. Nathan, N. Rifai, R. B. D'Agostino Sr., and P. W.F. Wilson Fasting Plasma Homocysteine Levels in the Insulin Resistance Syndrome: The Framingham Offspring Study Diabetes Care, August 1, 2001; 24(8): 1403 - 1410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H. Serne, R. O.B. Gans, J. C. ter Maaten, G.-J. Tangelder, A. J.M. Donker, and C. D.A. Stehouwer Impaired Skin Capillary Recruitment in Essential Hypertension Is Caused by Both Functional and Structural Capillary Rarefaction Hypertension, August 1, 2001; 38(2): 238 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.D. Hughes and S. Thom Wearing your heart in your sleeve? Eur. Heart J., July 1, 2001; 22(13): 1071 - 1073. [PDF]
|
|
|
|
|
|
D. J. Freeman, J. Norrie, N. Sattar, R. D. G. Neely, S. M. Cobbe, I. Ford, C. Isles, A. R. Lorimer, P. W. Macfarlane, J. H. McKillop, et al. Pravastatin and the Development of Diabetes Mellitus : Evidence for a Protective Treatment Effect in the West of Scotland Coronary Prevention Study Circulation, January 23, 2001; 103(3): 357 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H Serne, R. O.B Gans, J. C ter Maaten, P. M ter Wee, A. J.M Donker, and C. D.A Stehouwer Capillary recruitment is impaired in essential hypertension and relates to insulin's metabolic and vascular actions Cardiovasc Res, January 1, 2001; 49(1): 161 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hammoud, J.-F. Tanguay, and M. G. Bourassa Management of coronary artery disease: therapeutic options in patients with diabetes J. Am. Coll. Cardiol., August 1, 2000; 36(2): 355 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Mather, S. Verma, B. Corenblum, and T. J. Anderson Normal Endothelial Function Despite Insulin Resistance in Healthy Women with the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1851 - 1856. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Ryan, D. McInerney, D. Owens, P. Collins, A. Johnson, and G.H. Tomkin Diabetes and the Mediterranean diet: a beneficial effect of oleic acid on insulin sensitivity, adipocyte glucose transport and endothelium-dependent vasoreactivity QJM, February 1, 2000; 93(2): 85 - 91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Cleland, J. R. Petrie, M. Small, H. L. Elliott, and J. M. C. Connell Insulin Action Is Associated With Endothelial Function in Hypertension and Type 2 Diabetes Hypertension, January 1, 2000; 35(1): 507 - 511. [Abstract] [Full Text] [PDF]
|
|