Hostname: page-component-76fb5796d-9pm4c Total loading time: 0 Render date: 2024-04-27T02:47:03.828Z Has data issue: false hasContentIssue false
  • English
  • Français

Enhanced contractility in coronary arteries of diabetic pigs is prevented by exercise

Published online by Cambridge University Press:  09 March 2007

EA Mokelke ,
Q Hu ,
JR Turk  and
M Sturek
EA Mokelke
Affiliation:
Departments of Medical Pharmacology and Physiology, Internal Medicine and the Diabetes and Cardiovascular Biology Program, University of Missouri, Columbia, MO 65212, USA
Q Hu
Affiliation:
Departments of Medical Pharmacology and Physiology, Internal Medicine and the Diabetes and Cardiovascular Biology Program, University of Missouri, Columbia, MO 65212, USA
JR Turk
Affiliation:
Departments of Medical Pharmacology and Physiology, Internal Medicine and the Diabetes and Cardiovascular Biology Program, University of Missouri, Columbia, MO 65212, USA
M Sturek*
Affiliation:
Biomedical Sciences, University of Missouri, Columbia, MO 65212, USA
*
*sturekm@missouri.edu
Get access

Abstract

We hypothesized that hyperlipidaemia, diabetes and diabetic dyslipidaemia increase the contractility of coronary arteries in swine, and that exercise would prevent this enhanced contractility. We further hypothesized that this enhanced contractility is associated with elevated potassium (K+) channel activity, consistent with the idea that certain disease states, as in hypertension, result in a compensatory upregulation in K+ channels. Swine were assigned to one of the following groups: control, standard chow (C; n=6); hyperlipidaemic, high-fat chow (H; n=5); diabetic, standard chow (D; n=7); diabetic, high-fat chow (‘diabetic dyslipidaemic’, DD; n=12); or exercise-trained DD (DDX; n=9). High-fat chow consisted of standard pig chow with added cholesterol (2%) and coconut oil. Endothelium-denuded segments from D, DD and DDX animals showed enhanced contractility to prostaglandin F2α (PGF2α) compared with C, while segments from H, D and DD showed enhanced contractility to endothelin-1 (ET-1) compared with C and DDX (P<0.05). The enhanced contractility was not accompanied by differences in K+ channel contribution to force reduction. There was no effect of the treatments on expression of the endothelin receptor A or endothelin receptor B. A possible mechanism for the enhanced vasoreactivity of coronary arteries of H, D and DD swine is an alteration in the signalling pathways of ET-1- and PGF2α-induced contraction. Exercise prevented the increase in contractility to ET-1, but not to PGF2α, reinforcing the concept of vasoconstrictor specificity.

Keywords

diabetic dyslipidaemiaendothelin-1prostaglandinsmooth musclepotassium channels
Type
Research Article
Information
Equine and Comparative Exercise Physiology , Volume 1 , Issue 1 , February 2004 , pp. 71 - 80
Copyright
Copyright © Cambridge University Press 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Kannel, WB and McGee, DL (1979). Diabetes and cardiovascular disease: The Framingham study. Journal of the American Medical Association 241: 2035–2038.CrossRefGoogle ScholarPubMed
2Raman, M and Nesto, RW (1996). Heart disease in diabetes mellitus. Endocrinology and Metabolism Clinics of North America 25: 425–438.CrossRefGoogle ScholarPubMed
3Agrawal, DK, Bhimji, S and McNeill, HH (1987). Effect of chronic experimental diabetes on vascular smooth muscle function in rabbit carotid artery. Journal of Cardiovascular Pharmacology 9: 584–593.CrossRefGoogle ScholarPubMed
4Wamhoff, BR, Dixon, JL and Sturek, M (2002). Atorvastatin treatment prevents alterations in coronary smooth muscle nuclear Ca2+ signaling associated with diabetic dyslipidaemia. Journal of Vascular Research 39: 208–220.CrossRefGoogle Scholar
5Agrawal, DK and McNeill, JH (1987). Vascular responses to agonists in rat mesenteric artery from diabetic rats. Canadian Journal of Physiology and Pharmacology 65: 1484–1490.CrossRefGoogle ScholarPubMed
6Ramanadham, S, Lyness, WH and Tenner, TE (1984). Alterations in aortic and tail artery reactivity to agonists after streptozotocin treatment. Canadian Journal of Physiology and Pharmacology 62: 418–423.CrossRefGoogle ScholarPubMed
7Mokelke, EA, Hu, Q, Song, M, Toro, L, Reddy, HK and Sturek, M (2003). Altered functional coupling of K+ channels in diabetic dyslipidemic pigs is prevented by exercise. Journal of Applied Physiology 95: 1179–1193.CrossRefGoogle ScholarPubMed
8Nelson, MT and Quayle, JM (1995). Physiological roles and properties of potassium channels in arterial smooth muscle. American Journal of Physiology. Cell Physiology 268: C799–C822.CrossRefGoogle ScholarPubMed
9El-Kashef, H (1996). Hyperglycemia increased the responsiveness of isolated rabbit's pulmonary arterial rings to serotonin. Pharmacology 53: 151–159.CrossRefGoogle ScholarPubMed
10Hattori, Y, Kawasaki, H, Fukao, M, Gando, S, Akaishi, Y and Kanno, M (1996). Diminishment of contractions associated with depolarization-evoked activation of Ca2+ channels in diabetic rat aorta. Journal of Vascular Research 33: 454–462.CrossRefGoogle ScholarPubMed
11Sullivan, S and Sparks, HV (1979). Diminished contractile response of aortas from diabetic rabbits. American Journal of Physiology 236: H301–H306.Google ScholarPubMed
12Dixon, JL, Stoops, JD, Parker, JL, Laughlin, MH, Weisman, GA and Sturek, M (1999). Dyslipidaemia and vascular dysfunction in diabetic pigs fed an atherogenic diet. Arteriosclerosis, Thrombosis and Vascular Biology 19: 2981–2992.CrossRefGoogle ScholarPubMed
13Abebe, W, Harris, KH and MacLeod, KM (1990). Enhanced contractile responses of arteries from diabetic rats to α1-adrenoceptor stimulation in the absence and presence of extracellular calcium. Journal of Cardiovascular Pharmacology 16: 239–248.CrossRefGoogle Scholar
14Hill, JF, Dixon, JL and Sturek, M (2001). Effect of atorvastatin on intracellular calcium uptake in coronary smooth muscle cells from diabetic pigs fed an atherogenic diet. Atherosclerosis 159: 117–124.CrossRefGoogle ScholarPubMed
15Liu, Y, Jones, AW and Sture, kM (1995). Ca2+-dependent K+ current in arterial smooth muscle cells from aldosterone-salt hypertensive rats. American Journal of Physiology. Heart and Circulatory Physiology 269: H1246–H1257.CrossRefGoogle Scholar
16Liu, YP, Hudetz, AG, Knaus, HG and Rusch, NJ (1998). Increased expression of Ca2+-sensitive K+ channels in the cerebral microcirculation of genetically hypertensive rats; evidence for their protection against cerebral vasospasm. Circulation Research 82: 729–737.CrossRefGoogle ScholarPubMed
17Bowles, DK, Laughlin, MH and Sturek, M (1995). Exercise training alters the Ca2+ and contractile responses of coronary arteries to endothelin. Journal of Applied Physiology 78: 1079–1087.CrossRefGoogle ScholarPubMed
18Phillips, RW, Panepinto, LM, Spangler, R and Westmoreland, N (1982). Yucatan miniature swine as a model for the study of human diabetes mellitus. Diabetes 31: 30–36.CrossRefGoogle Scholar
19Mills, PC, Marlin, DJ, Demoncheaux, E, Scott, C, Casas, L, Smith, NC, et al. (1996). Nitric oxide and exercise in the horse. Journal of Physiology (London) 495: 863–874.CrossRefGoogle ScholarPubMed
20Manohar, M (1988). Costal vs. crural diaphragmatic blood flow during submaximal and near-maximal exercise in ponies. Journal of Applied Physiology 65: 1514–1519.CrossRefGoogle ScholarPubMed
21Dixon, JL, Shen, S, Vuchetich, JP, Wysocka, E, Sun, GY and Sturek, M (2002). Increased atherosclerosis in diabetic dyslipidemic swine: protection by atorvastatin involves decreased VLDL triglycerides but minimal effects on the lipoprotein profile. Journal of Lipid Research 43: 1618–1629.CrossRefGoogle ScholarPubMed
22Boullion, RD, Molelke, EA, Wamhoff, BR, Otis, CR, Wenzel, J, Dixon, JL, et al. (2003). Porcine model of diabetic dyslipidaemia: insulin and feed algorithms for mimicking diabetes in humans. Comparative Medicine 53: 42–52.Google ScholarPubMed
23Cooperstein, SJ and Watkins, D (1981). The Islets of Langerhans. New York: Academic Press, pp. 387–425.CrossRefGoogle Scholar
24Stehno-Bittel, L, Laughlin, MH and Sturek, M (1990). Exercise training alters Ca release from coronary smooth muscle sarcoplasmic reticulum. American Journal of Physiology. Heart and Circulatory Physiology 259: H643–H647.CrossRefGoogle ScholarPubMed
25Stehno-Bittel, L, Laughlin, MH and Sturek, M (1991). Exercise training depletes sarcoplasmic reticulum calcium in coronary smooth muscle. Journal of Applied Physiology 71: 1764–1773.CrossRefGoogle ScholarPubMed
26McAllister, RM and Laughlin, MH (1997). Short-term exercise training alters responses of porcine femoral and brachial arteries. Journal of Applied Physiology 82: 1438–1444.CrossRefGoogle ScholarPubMed
27Jones, AW, Rubin, LJ and Magliola, L (1999). Endothelin-1 sensitivity of porcine coronary arteries is reduced by exercise training and is gender dependent. Journal of Applied Physiology 87: 1172–1177.CrossRefGoogle ScholarPubMed
28Nelson, MT, Patlak, JB, Worley, JF and Standen, NB (1990). Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone. American Journal of Physiology. Cell Physiology 259: C3–C18.CrossRefGoogle ScholarPubMed
29Brayden, JE and Nelson, MT (1992). Regulation of arterial tone by activation of calcium-dependent potassium channels. Science 256: 532–535.CrossRefGoogle ScholarPubMed
30Weber, LP, Chow, WL, Abebe, W and MacLeod, KM (1996). Enhanced contractile responses of arteries from streptozotocin diabetic rats to sodium fluoride. British Journal of Pharmacology 118: 115–122.CrossRefGoogle ScholarPubMed
31Abebe, W and MacLeod, KM (1990). Protein kinase Cmediated contractile responses of arteries from diabetic rats. British Journal of Pharmacology 225: 29–36.Google Scholar
32Wamhoff, BR, Dixon, JL and Sturek, M (2001). Exercise training prevents altered coronary smooth muscle L-type calcium channel function in diabetic dyslipidaemia. Circulation 104: II 157.Google Scholar
33Hattori, Y, Kawasaki, H and Kanno, M (1999). Increased contractile responses to endothelin-1 and U46619 via a protein kinase C-mediated nifedipine-sensitive pathway in diabetic rat aorta. Research Communications in Molecular Pathology and Pharmacology 104: 73–80.Google Scholar
34Davis, SF, Yeung, AC, Meredith, T, Charbonneau, F, Ganz, P, Selwyn, AP, et al. (1996). Early endothelial dysfunction predicts the development of transplant coronary artery disease at 1 year post-transplant. Circulation 93: 457–462.CrossRefGoogle Scholar
35Liu, Y and Sturek, M (1996). Attenuation of endothelin-1-induced calcium responses by tyrosine kinase inhibitors in vascular smooth muscle cells. American Journal of Physiology. Cell Physiology 270: C1825–C1833.CrossRefGoogle ScholarPubMed
36Lee, DL, Wamhoff, BR, Katwa, LC, Reddy, HK, Voelker, DJ, Dixon, JL, et al. (2003). Increased endothelin-induced Ca2+ signaling, tyrosine phosphorylation, and coronary artery disease in diabetic dyslipidemic swine are prevented by atorvastatin. Arteriosclerosis, Thrombosis and Vascular Biology 306: 132–140.Google ScholarPubMed
37Campbell, WB and Halushka, PV (1996). Lipid-derived autanoids, eicosanoids and platelet-activating factor. In: Hardman, JG, and Limbird, LE (eds) Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York: McGraw-Hill, pp. 601–610.Google Scholar
38Abebe, W and MacLeod, KM (1992). Augmented inositol phosphate production in mesenteric arteries from diabetic rats. European Journal of Pharmacology. Molecular Pharmacology 225: 29–36.CrossRefGoogle ScholarPubMed
39Usune, S, Katsuragi, T and Furukawa, T (1989). Two phases of the prostaglandin F2α-induced contraction in guinea pig taenia coli involve different Ca2+ channels. Naunyn-Schmiedeberg's Archives of Pharmacology 340: 437–441.CrossRefGoogle Scholar
40Rembold, CM and Chen, XL (1998). The buffer barrier hypothesis, [Ca2+]i homogeneity and sarcoplasmic reticulum function in swine carotid artery. Journal of Physiology (London) 513: 477–492.CrossRefGoogle ScholarPubMed
41Yoshikawa, A, Van Breemen, C and Isenberg, G (1996). Buffering of plasmalemmal Ca2+ current by sarcoplasmic reticulum of guinea pig urinary bladder myocytes. American Journal of Physiology. Cell Physiology 271: C833–C841.Google ScholarPubMed