| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Physiology, University of Saskatchewan, Saskatchewan, Canada, S7N 5E5
Abstract
Enhancement of the heme oxygenase/carbon monoxide (HO/CO) system has been shown to lower blood pressure (BP) in young (8 weeks), but not in adult (20 weeks) spontaneously hypertensive (SHR) rats. The reasons for this selective effect still remain puzzling. We investigated the effects of hemin on the HO/CO system of the pulmonary artery (PA) in SHR and Wistar-Kyoto (WKY) rats at different ages and evaluated the hemin-dependent changes in sGC and cGMP pathways. Hemin administration resulted in an evident reduction of BP (from 148.6 ± 3.2 to 125.8 ± 2.6 mmHg, P < 0.01) in young, but not in prehypertensive (4 weeks) or adult SHR or WKY rats at all ages. Coadministration of the HO inhibitor, chromium mesoporphyrin, with hemin, cancelled the BP-lowering effect of hemin. Remarkably, lower expression levels of HO-1, HO-2, and sGC paralleled with reduced HO activity and cGMP content were observed in PA from 8-week SHR rats, but not from adult SHR or WKY rats of all ages. Interestingly, hemin treatment restored these deficiencies, although the expression level of non-inducible HO-2 protein remained unchanged. We conclude that in young and prehypertensive SHR rats, an impaired HO/CO-sGC/cGMP system in the PA might be indicative of the pathogenesis and development of hypertension. In contrast, the HO/CO system in the PA of adult SHR rats was upregulated as a compensatory reaction to elevated BP and desensitization of the downstream targets of the sGC/cGMP pathway occurred.
Key Words: carbon monoxide • gasotransmitter • heme oxygenase • hypertension • pulmonary artery
This article has been cited by other articles:
|
|
 |
|
  G. Alba, R. El Bekay, P. Chacon, M. E. Reyes, E. Ramos, J. Olivan, J. Jimenez, J. M. Lopez, J. Martin-Nieto, E. Pintado, et al. Heme oxygenase-1 expression is down-regulated by angiotensin II and under hypertension in human neutrophils J. Leukoc. Biol., August 1, 2008; 84(2): 397 - 405. [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]
|
|
|
|
 |
|
 E. A. Herrera, R. V. Reyes, D. A. Giussani, R. A. Riquelme, E. M. Sanhueza, G. Ebensperger, P. Casanello, N. Mendez, R. Ebensperger, E. Sepulveda-Kattan, et al. Carbon monoxide: a novel pulmonary artery vasodilator in neonatal llamas of the Andean altiplano Cardiovasc Res, January 1, 2008; 77(1): 197 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Taskiran, T. Nesil, and K. Alkan Mitochondrial oxidative stress in female and male rat brain after ex vivo carbon monoxide treatment Human and Experimental Toxicology, August 1, 2007; 26(8): 645 - 651. [Abstract] [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
