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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Erectile dysfunction: an early marker for hypertension? A longitudinal study in spontaneously hypertensive rats

¹Pelvipharm, Domaine Centre National de la Recherche Scientifique (CNRS), Gif sur Yvette; ²CNRS Unité propre de Recherche de l’Enseignement Supérieur 7053, University Paris-XII, Créteil Cedex; ⁴Groupe de Recherche en Urologie, Unité propre de Recherche de l’Enseignement Supérieur Associée, Equipe d’Accuol 1602, University of Paris South, Le Kremlin Bicêtre, France; and ³Cardiovascular Clinical Research and Development, Novartis, East Hanover, New Jersey

Submitted 20 January 2004 ; accepted in final form 28 July 2004

Erectile dysfunction (ED) is another manifestation of vascular disease. We evaluated the natural history of ED in the spontaneously hypertensive rat (SHR) and the respective participation of associated pathophysiological modifications, i.e., endothelial dysfunction and tissue remodeling. SHR and their normotensive counterparts [Wistar-Kyoto rats (WKY)] of 6, 12, and 24 wk 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 wk of age in erectile tissue of SHR compared with WKY (maximal relaxation: –19.2 ± 2.8% vs. –28.3 ± 3.9%, P < 0.001) but only at 24 wk 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 wk of age. Major modifications in the distribution of collagen I, III, and V in SHR occur in both types of tissue and are detectable sooner in erectile tissue compared with aortic tissue. The onset of ED is detectable before the onset of hypertension in the SHR. Structural and functional alterations, while similar, occur earlier in erectile compared with 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.

hypertension; endothelial dysfunction; remodeling

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