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1 Domaine Centre National de Recherche Scientifique, Pelvipharm, Gif sur Yvette, France
2 University Paris-XII, CNRS UPRESA 7053, Creteil, France
3 Cardiovascular Clinical Research and Development, Novartis, East Hanover, New Jersey, USA
4 Domaine Centre National de Recherche Scientifique, Pelvipharm, Gif sur Yvette, France; University of Paris South, Groupe de Recherche en Urologie, UPRES EA 1602, Le Kremlin Bicetre, France
* To whom correspondence should be addressed. E-mail: giuliano{at}cyber-sante.org.
Erectile dysfunction (ED) is another manifestation of vascular disease. We evaluated the natural history of ED in the SHR and the respective participation of associated pathophysiological modifications i.e. endothelial dysfunction and tissue remodeling. SHR and their normotensive counterparts (WKY) of 6, 12 and 24 weeks of age (n=12) were used to evaluate erectile function, erectile and aortic tissue reactivity and remodeling. Erectile responses in SHR are reduced at all ages (p<0.001). In both aortic and erectile tissues of SHR and WKY, relaxations to ACh are altered progressively with age, although more markedly in SHR. They are decreased at 12 weeks of age in erectile tissue of SHR compared to WKY (maximal relaxation: -19.2 ± 2.8% vs -28.3 ± 3.9, p<0.001) but only at 24 weeks of age in aortas (-47.9 ± 6.4% vs -90.5 ± 2.9, p<0.001). Relaxations to sodium nitroprusside are unaltered in aortic rings of both strains but enhanced in erectile tissue of SHR at 12 weeks of age. Major modifications in the distribution of collagen I, III and V in SHR occur in both type of tissue and are detectable sooner in erectile tissue compared to aortic tissue. The onset of ED is detectable prior to the onset of hypertension in the SHR. Structural and functional alterations, while similar, occur earlier in erectile compared to vascular tissue. If confirmed in humans, ED could be an early warning sign for hypertension and common therapeutic strategies targeting both ED and hypertension could be investigated.
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