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(Hypertension. 2006;48:685.)
© 2006 American Heart Association, Inc.

Original Articles

Sustained Normalization of High Blood Pressure in Spontaneously Hypertensive Rats by Implanted Hemin Pump

Rui Wang; Rany Shamloul; Xiaoxia Wang; Qinghe Meng; Lingyun Wu

From the Departments of Physiology (R.W., R.S.), Pharmacology (X.W., L.W.), and Pathology (Q.M.), University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and the Department of Biology (R.W.), Lakehead University, Thunder Bay, Ontario, Canada.

Correspondence to Rui Wang, Office of VP Research, Lakehead University, 955 Oliver Rd, Thunder Bay, Ontario, Canada P7B 5E1. E-mail rwang{at}lakeheadu.ca

Treatment of established hypertension, especially for prolonged control of this pathogenic process, represents a great challenge. To upregulate the expression of heme oxygenase (HO) to lower blood pressure (BP) of spontaneously hypertensive rats (SHRs), we administered hemin to 12-week-old adult SHRs through subcutaneously implanted osmotic minipumps for 3 consecutive weeks (the hemin protocol). Systolic BP of SHRs was normalized 123±2 mm Hg (n=20; P<0.001) and this normalization maintained for 9 months after the removal of hemin pumps. At the end of the hemin protocol, HO-1 expression, HO activity, soluble guanylyl cyclase expression, and cGMP content were all increased, but phosphodiesterase-5 expression was downregulated in the mesenteric arteries. The hemin protocol also reversed SHR-featured arterial eutrophic inward remodeling and decreased expression levels of vascular endothelial growth factor. These changes lasted 9 months after the hemin protocol. Our study, thus, formulates a novel hemin protocol that will not only normalize BP in SHRs with established hypertension but, more importantly, will also provide long-lasting antihypertension protection. Sustained upregulation of HO-1–linked signaling pathways and reversal of vascular remodeling in peripheral blood vessels mediate likely the antihypertensive effect of the hemin protocol.

Key Words: hypertension • hemin • heme oxygenase • blood pressure • remodeling

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Induction of Heme Oxygenase: Can It Really Reverse Hypertension?

William H. Beierwaltes
Hypertension 2006 48: 555-557. [Full Text] [PDF]

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