(Hypertension. 1995;25:994-1002.)
© 1995 American Heart Association, Inc.
Articles |
Hemodynamic and Renal Responses to Chronic Hyperinsulinemia in Obese, Insulin-Resistant Dogs
From the Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson.
Abstract We previously reported that chronic hyperinsulinemia does not cause hypertension in normal insulin-sensitive dogs. However, resistance to the metabolic and vasodilator effects of insulin may be a prerequisite for hyperinsulinemia to elevate blood pressure. The present study tested this hypothesis by comparing the control of systemic hemodynamics and renal function during chronic hyperinsulinemia in instrumented normal conscious dogs (n=6) and in dogs made obese and insulin resistant by feeding them a high-fat diet for 6 weeks (n=6). After 6 weeks of the high-fat diet, body weight increased from 24.0±1.2 to 40.9±1.2 kg, arterial pressure rose from 83±5 to 106±4 mm Hg, and cardiac output rose from 2.98±0.29 to 5.27±0.54 L/min. Insulin sensitivity, assessed by fasting hyperinsulinemia and by the hyperinsulinemic euglycemic clamp technique, was markedly reduced in obese dogs. Insulin infusion (1.0 mU/kg per minute for 7 days) in obese dogs elevated plasma insulin from 42±12 µU/mL to 95 to 219 µU/mL but failed to increase arterial pressure, which averaged 106±4 mm Hg during control and 102±4 mm Hg during 7 days of insulin infusion. Hyperinsulinemia for 7 days in obese dogs elevated heart rate from 116±8 to 135±7 beats per minute but caused no significant changes in cardiac output, in contrast to normal dogs (n=6), in which marked increases in cardiac output (31±5% after 7 days) and decreases in total peripheral resistance occurred during chronic insulin infusion. Thus, chronic hyperinsulinemia did not raise blood pressure in obese dogs even though they were resistant to the metabolic and vasodilator effects of insulin. These observations provide no evidence that hyperinsulinemia causes hypertension, even in the presence of insulin resistance, in obese dogs.
Key Words: obesity • insulin • cardiac output • vasodilation • heart rate • kidney • blood flow
This article has been cited by other articles:
 |
|
 |
|
  E. J. Belin de Chantemele, K. Muta, J. Mintz, M. L. Tremblay, M. B. Marrero, D. J. Fulton, and D. W. Stepp Protein Tyrosine Phosphatase 1B, a Major Regulator of Leptin-Mediated Control of Cardiovascular Function Circulation, September 1, 2009; 120(9): 753 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Brands, T. D. Bell, N. A. Rodriquez, P. Polavarapu, and D. Panteleyev Chronic glucose infusion causes sustained increases in tubular sodium reabsorption and renal blood flow in dogs Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R265 - R271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zhang, J. D. Knudson, S. Setty, A. Araiza, U. D. Dincer, L. Kuo, and J. D. Tune Coronary arteriolar vasoconstriction to angiotensin II is augmented in prediabetic metabolic syndrome via activation of AT1 receptors Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2154 - H2162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Morgan, S. Obici, and L. Rossetti Hypothalamic Responses to Long-chain Fatty Acids Are Nutritionally Regulated J. Biol. Chem., July 23, 2004; 279(30): 31139 - 31148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Aneja, F. El-Atat, S. I. McFarlane, and J. R. Sowers Hypertension and Obesity Recent Prog. Horm. Res., January 1, 2004; 59(1): 169 - 205. [Abstract] [Full Text]
|
|
|
|
|
|
S. Zhang, Y. Yang, B. C. Kone, J. C. Allen, and A. M. Kahn Insulin-Stimulated Cyclic Guanosine Monophosphate Inhibits Vascular Smooth Muscle Cell Migration by Inhibiting Ca/Calmodulin-Dependent Protein Kinase II Circulation, March 25, 2003; 107(11): 1539 - 1544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. HENEGAR, S. A. BIGLER, L. K. HENEGAR, S. C. TYAGI, and J. E. HALL Functional and Structural Changes in the Kidney in the Early Stages of Obesity J. Am. Soc. Nephrol., June 1, 2001; 12(6): 1211 - 1217. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. W. Brands, A. E. Hailman, and S. M. Fitzgerald Long-Term Glucose Infusion Increases Arterial Pressure in Dogs With Cyclooxygenase-2 Inhibition Hypertension, February 1, 2001; 37(2): 733 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. T. Cefalu Insulin Resistance: Cellular and Clinical Concepts Experimental Biology and Medicine, January 1, 2001; 226(1): 13 - 26. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. C. ter Maaten, S. J. L. Bakker, E. H. Serne, P. M. ter Wee, A. J. M. Donker, and R. O. B. Gans Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlate with salt sensitivity in normal subjects Nephrol. Dial. Transplant., October 1, 1999; 14(10): 2357 - 2363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Keen, M. W. Brands, M. J. Smith Jr, and J. E. Hall Maintenance of Baseline Angiotensin II Potentiates Insulin Hypertension in Rats Hypertension, February 1, 1998; 31(2): 637 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Brands, D. L. Harrison, H. L. Keen, A. Gardner, E. W. Shek, and J. E. Hall Insulin-Induced Hypertension in Rats Depends on an Intact Renin-Angiotensin System Hypertension, April 1, 1997; 29(4): 1014 - 1019. [Abstract] [Full Text]
|
|
|
|
|
|
J. R. Sowers Insulin and Insulin-Like Growth Factor in Normal and Pathological Cardiovascular Physiology Hypertension, March 1, 1997; 29(3): 691 - 699. [Full Text]
|
|
|
|
|
|
M. K. McKay and R. L. Hester Role of Nitric Oxide, Adenosine, and ATP-Sensitive Potassium Channels in Insulin-Induced Vasodilation Hypertension, August 1, 1996; 28(2): 202 - 208. [Abstract] [Full Text]
|
|