Published online before print July 22, 2002, doi: 10.1161/01.HYP.0000028488.71068.16
(Hypertension. 2002;40:315.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
Selective Regulation of Blood Pressure by Heme Oxygenase-1 in Hypertension
From the Department of Physiology, University of Saskatchewan, Saskatoon, Canada.
Correspondence to Prof Rui Wang, Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada S7N 5E5. E-mail wangrui{at}duke.usask.ca
Heme oxygenase (HO) and carbon monoxide (CO) participate in the homeostatic control of cardiovascular functions, including the regulation of blood pressure (BP). Upregulation of the HO/CO system has been shown to lower BP in young (8 weeks) but not in adult (20 weeks) spontaneously hypertensive rats (SHR). The underlying mechanism for this selective effect, however, has been unknown and was investigated in the present study. The administration of hemin resulted in a marked decrease in BP (from 148.6±3.2 to 125.8±2.6 mm Hg, P<0.01) in young but not in prehypertensive (4 weeks) or adult SHR or Wistar-Kyoto rats at all ages. The inhibition of HO with chromium mesoporphyrin abrogated the BP-lowering effect of hemin. Significantly lower expression levels of HO-1 and soluble gyanylyl cyclase (sGC) as well as reduced cGMP content were detected in 8-week SHR but not in adult SHR or Wistar-Kyoto rats of all ages. These deficiencies were all corrected by hemin treatment. The expression of HO-2 protein was not different among all animal groups tested and not affected by hemin treatment. Desensitization of the sGC/cGMP pathway in adult SHR was demonstrated by the reduced vasorelaxant potency of the sGC activator 3-(5' -hydroxymethyl-2-'furyl)-1-benzylindazole. Thus, in young and prehypertensive SHR, a defective HO/CO-sGC/cGMP system might constitute a pathogenic mechanism for the development of hypertension. The HO/CO-sGC/cGMP system appears normal in adult SHR, but desensitization of the downstream targets of the system to sGC/cGMP may endow SHR at this stage a persistent hypertension status.
Key Words: cyclic GMP • hypertension, experimental • rats, spontaneously hypertensive • mesenteric arteries • heme oxygenase
This article has been cited by other articles:
 |
|
 |
|
  A. Jadhav and J. F. Ndisang Heme Arginate Suppresses Cardiac Lesions and Hypertrophy in Deoxycorticosterone Acetate-Salt Hypertension Experimental Biology and Medicine, July 1, 2009; 234(7): 764 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cheng, A. M. Noordeloos, V. Jeney, M. P. Soares, F. Moll, G. Pasterkamp, P. W. Serruys, and H. J. Duckers Heme Oxygenase 1 Determines Atherosclerotic Lesion Progression Into a Vulnerable Plaque Circulation, June 16, 2009; 119(23): 3017 - 3027. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Ndisang and A. Jadhav Up-Regulating the Hemeoxygenase System Enhances Insulin Sensitivity and Improves Glucose Metabolism in Insulin-Resistant Diabetes in Goto-Kakizaki Rats Endocrinology, June 1, 2009; 150(6): 2627 - 2636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Ndisang, N. lane, and A. Jadhav The Heme Oxygenase System Abates Hyperglycemia in Zucker Diabetic Fatty Rats by Potentiating Insulin-Sensitizing Pathways Endocrinology, May 1, 2009; 150(5): 2098 - 2108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Brunt, M. R. Tsuji, J. H. Lai, R. T. Kinobe, W. Durante, W. C. Claycomb, C. A. Ward, and L. G. Melo Heme Oxygenase-1 Inhibits Pro-Oxidant Induced Hypertrophy in HL-1 Cardiomyocytes Experimental Biology and Medicine, May 1, 2009; 234(5): 582 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Ndisang, N. Lane, and A. Jadhav Upregulation of the heme oxygenase system ameliorates postprandial and fasting hyperglycemia in type 2 diabetes Am J Physiol Endocrinol Metab, May 1, 2009; 296(5): E1029 - E1041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Ndisang and A. Jadhav Heme oxygenase system enhances insulin sensitivity and glucose metabolism in streptozotocin-induced diabetes Am J Physiol Endocrinol Metab, April 1, 2009; 296(4): E829 - E841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jadhav, E. Torlakovic, and J. F. Ndisang Interaction Among Heme Oxygenase, Nuclear Factor-{kappa}B, and Transcription Activating Factors in Cardiac Hypertrophy in Hypertension Hypertension, November 1, 2008; 52(5): 910 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Chang, L. Wu, and R. Wang Inhibition of vascular smooth muscle cell proliferation by chronic hemin treatment Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H999 - H1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-G. Sun, Y.-X. Cao, W.-W. Wang, S.-F. Ma, T. Yao, and Y.-C. Zhu Hydrogen sulphide is an inhibitor of L-type calcium channels and mechanical contraction in rat cardiomyocytes Cardiovasc Res, September 1, 2008; 79(4): 632 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Datla, G. J. Dusting, T. A. Mori, C. J. Taylor, K. D. Croft, and F. Jiang Induction of Heme Oxygenase-1 In Vivo Suppresses NADPH Oxidase Derived Oxidative Stress Hypertension, October 1, 2007; 50(4): 636 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-C. Lo, P.-J. Lu, W.-Y. Ho, M. Hsiao, and C.-J. Tseng Induction of Heme Oxygenase-1 Is Involved in Carbon Monoxide-Mediated Central Cardiovascular Regulation J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 8 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Ryter, J. Alam, and A. M. K. Choi Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications Physiol Rev, April 1, 2006; 86(2): 583 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Achouh, S. Simonet, C. Badier-Commander, C. Chardigny, C. Vayssettes-Courchay, R. Zegdi, Z. Khabbaz, J.-N. Fabiani, and T. J. Verbeuren The induction of heme oxygenase 1 decreases contractility in human internal thoracic artery and radial artery grafts J. Thorac. Cardiovasc. Surg., December 1, 2005; 130(6): 1573 - 1580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wu and R. Wang Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications Pharmacol. Rev., December 1, 2005; 57(4): 585 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Bolognesi, D Sacerdoti, M Di Pascoli, P Angeli, S Quarta, A Sticca, P Pontisso, C Merkel, and A Gatta Haeme oxygenase mediates hyporeactivity to phenylephrine in the mesenteric vessels of cirrhotic rats with ascites Gut, November 1, 2005; 54(11): 1630 - 1636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-M. Hu, Y.-H. Chen, M.-T. Chiang, and L.-Y. Chau Heme Oxygenase-1 Inhibits Angiotensin II-Induced Cardiac Hypertrophy In Vitro and In Vivo Circulation, July 20, 2004; 110(3): 309 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Roman Gene Therapy and Heme Oxygenase Coming of Age Hypertension, June 1, 2004; 43(6): 1173 - 1174. [Full Text] [PDF]
|
|
|
|
|
|
F. K. Johnson, W. Durante, K. J. Peyton, and R. A. Johnson Heme oxygenase-mediated endothelial dysfunction in DOCA-salt, but not in spontaneously hypertensive, rat arterioles Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1681 - H1687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Naik and B. R. Walker Heme oxygenase-mediated vasodilation involves vascular smooth muscle cell hyperpolarization Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H220 - H228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Ndisang, L. Wu, W. Zhao, and R. Wang Induction of heme oxygenase-1 and stimulation of cGMP production by hemin in aortic tissues from hypertensive rats Blood, May 15, 2003; 101(10): 3893 - 3900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Ndisang and R. Wang Alterations in Heme Oxygenase/Carbon Monoxide System in Pulmonary Arteries in Hypertension Experimental Biology and Medicine, May 1, 2003; 228(5): 557 - 563. [Abstract] [Full Text] [PDF]
|
|