Increased intracavernosal pressure response in hypertensive rats after chronic hemin treatment.
BACKGROUND
Erectile dysfunction (ED) is increased in prevalence in patients with arterial hypertension. Whether upregulation of heme oxygenase (HO) expression could improve penile erection has been unknown.


OBJECTIVE
To correlate altered expression profiles of HO-1 and soluble guanylyl cyclase (sGC) in penile tissues with low intracavernosal pressure (ICP) in adult spontaneously hypertensive rats (SHR); and to investigate therapeutic effect of hemin-induced upregulation of HO-1 in penile tissues on ED developed in adult SHR.


METHODS
Intracavernosal pressure changes after electrical stimulation were monitored in adult SHR and age-matched normotensive Sprague-Dawley (SD) rats after chronic administration of either hemin or hydralazine. Expression levels of HO-1, HO-2, sGC, and phosphodiesterase type 5 (PDE5) were examined with Western blot.


RESULTS
Frequency-dependent ICP changes were reduced in adult SHR. Three weeks after hemin treatment, high blood pressure of SHR was normalized and ICP responses to electrical stimulations in SHR were significantly increased to the level of normotensive rats. Hydralazine-treated SHR had normalized blood pressure but unaltered low ICP response. Expression of HO-1 and sGC was upregulated and that of PDE5 downregulated in hemin-treated, but not hydralazine-treated, SHR.


CONCLUSIONS
Decreased erectile responses in adult SHR can be improved through chronic hemin treatment. Prolonged upregulation of HO-1 and sGC as well as lowered expression of PDE5 may at least partially explain the effect of hemin treatment on ICP. Upregulation of HO-1 may represent a novel therapeutic approach to treat ED.
Shamloul
Rany
R
Department of Physiology, University of Saskatchewan, Saskatoon, Canada.
Wang
Rui
R
Department of Physiology, University of Saskatchewan, Saskatoon, Canada;; Office of VP Research, Lakehead University, Thunder Bay, Ontario, Canada. Electronic address: rwang@lakeheadu.ca.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000187:drug effects; D006427:Hemin / Q000008:administration & dosage*; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010413:Penis / Q000098:blood supply / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D000071756:Soluble Guanylyl Cyclase; D014665:Vasodilator Agents / Q000008:administration & dosage*
D018160:Receptors, Cytoplasmic and Nuclear; D014665:Vasodilator Agents; D006830:Hydralazine; D006427:Hemin; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase