Effect of prolonged stimulation of the heme oxygenase/carbon monoxide system by hemin on blood pressure and penile erection of spontaneously hypertensive rats

Abstract

Essential hypertension (EH) is a risk factor for many cardiovascular disorders. Treatment of established EH, especially for prolonged control of this pathogenic process, represents a great challenge. Moreover, hypertension is considered an important risk factor for the development of many other diseases, e.g. erectile dysfunction. Hemin and other heme derivatives, e.g. heme-L-lysinate (HLL) and heme-L-arginate, have been used extensively to upregulate expression of heme oxygenase (HO) and production of endogenous carbon monoxide (CO). Short-term hemin administration for 4-5 days has been shown to markedly decrease high blood pressure (BP) in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) or Sprague Dawley (SD) rats. This short-term therapy was effective in treating young, but not adult SHR. In the present study, hemin (15 mg/kg/day) was administered to 12-week old adult SHR through subcutaneously implanted osmotic minipumps for 3 consecutive weeks (the hemin protocol). Into the second week of the hemin protocol, BP of SHR was normalized from 203.2 ± 2.5 to 123.4 ±1.9 mmHg (n=20, p