Published Online
on August 28, 2006

A more recent version of this article appeared on October 1, 2006

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Submitted on May 10, 2006
Revised on May 30, 2006

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

Rui Wang^*; Rany Shamloul; Xiaoxia Wang; Qinghe Meng; and 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.

^* To whom correspondence should be addressed. E-mail: rwang{at}lakeheadu.ca.

Abstract--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

Related Article:

Induction of Heme Oxygenase: Can It Really Reverse Hypertension?

William H. Beierwaltes
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