Differences between Candesartan and Hydralazine in the protection of penile structures in spontaneously hypertensive rats.
BACKGROUND
Previous studies indicate that angiotensin type I receptor antagonists present a beneficial effect on penile structures in hypertensive rats. However, at present there is no substantial information concerning the functional aspect of this class of antihypertensive drugs.


OBJECTIVE
To determine, by in vitro studies, functional effects of Candesartan in comparison with a traditional vasodilating agent, Hydralazine, on penile structures in a rat model of arterial hypertension.


METHODS
During 4 months, three groups of male spontaneously hypertensive rats (SHR) and one of Wistar-Kyoto (WKY) rats, as control group, were studied: SHR without treatment; SHR with Candesartan cilexetil 7.5 mg/kg/day; SHR with Hydralazine 50 mg/kg/day; and WKY rats without treatment. Cavernous smooth muscle strips were mounted in an organ bath system for in vitro studies. In addition, cavernous smooth muscle and vascular smooth muscle from cavernous arteries, cavernous tissue fibrosis, and collagen type III were also evaluated by immunohistochemistry.


RESULTS
After 4 months, SHR with Candesartan and Hydralazine showed similar reduction in blood pressure compared with untreated SHR. However, in vitro studies revealed that SHR with Candesartan displayed a better relaxation response to acetylcholine than SHR and SHR with Hydralazine (P < 0.01). Immunostaining indicates that only SHR with Candesartan and control WKY rats showed significantly lower values of: (i) cavernous smooth muscle (P < 0.01); (ii) vascular smooth muscle (P < 0.01); and (iii) collagen type III (P < 0.01) when compared with untreated SHR or SHR with Hydralazine. Additionally, SHR with Candesartan presented a higher endothelial nitric oxide synthase expression in sinusoidal endothelium in comparison with SHR, and SHR with Hydralazine (P < 0.01).


CONCLUSIONS
Candesartan presented equivalent blood pressure control compared with Hydralazine. However, only Candesartan showed a significant better response to acetylcholine, in in vitro studies, with a protective role against structural changes in vessels as well as in cavernous spaces of the erectile tissue.
Mazza
Osvaldo Néstor
ON
Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina.
Angerosa
Margarita
M
Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina.
Becher
Edgardo
E
Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina.
Toblli
Jorge Eduardo
JE
Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina. Electronic address: jtoblli@hospitalaleman.com.
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006830:Hydralazine / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D018783:Impotence, Vasculogenic / Q000188:drug therapy* / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D010413:Penis / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D006830:Hydralazine; D003094:Collagen; C081643:candesartan