Abstract
Androgen deprivation induces vascular dysfunction in which altered release and action of prostanoids has been extensively studied. On the other hand, the vascular organ-culture system has been reported as a valid model for phenotypic changes that occur in several cardiovascular pathologies. Since there are no studies analyzing the impact of androgenic loss on vascular vulnerability during induced vascular damage, the objective of this study was to analyze the possible preventive role of male sex hormones on the organ culture-induced vascular damage in rat aorta. The link to possible changes in gross structure was also analyzed. For this purpose, fresh and 20 h-cultured aortic arterial segments from intact and orchidectomized rats were used to analyze: (i) the release and vasomotor effect of the thromboxane A2 (TXA2), prostaglandin (PG) E2, PGF2α and PGI2; (ii) the vasodilator response induced by acetylcholine (ACh) as well as the involvement of prostanoids, in particular TXA2, in the ACh-induced response; (iii) the effect of activation of thromboxane/prostaglandin (TP) receptors on the ACh-induced response; and (iv) the vascular structure. The results showed that organ culture: i) increased production of prostanoids; ii) increased prostanoids-induced vasomotor responses; iii) decreased ACh-induced relaxation after incubation with indomethacin, a blocker of cyclooxygenases; iv) increased the ACh-induced relaxation after incubation with the TXA2 synthase inhibitor, furegrelate, more in arteries from orchidectomized rats than in those of intact rats; v) diminished ACh-induced relaxation after U-46619 incubation only in arteries from orchidectomized rats; and vi) preserved the integrity of the different vascular layers. These results showed the protective role of male sex hormones against the induced vascular damage, since a decreased deleterious effect of prostanoids, in particular that of TXA2, was observed in arteries from rats with intact gonadal function.
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