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Gonadal function protects against organ culture-induced vascular damage. Involvement of prostanoids
Diva M Villalpando1, Juan Gómez Rivas2, Daniel Flynn1
1Departamento de Fisiología, Facultad de Medicina, UAM, Spain.
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.
Insights
Male sex hormones protect against vascular damage by reducing the harmful effects of prostanoids, particularly thromboxane A2 (TXA2), in rat aorta organ cultures. This study highlights the protective role of androgens in maintaining vascular health.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Vascular Biology
Background:
- Androgen deprivation is linked to vascular dysfunction, with altered prostanoid activity being a key factor.
- Vascular organ culture serves as a model for studying cardiovascular pathologies.
- The impact of androgen loss on vascular vulnerability during induced damage remains understudied.
Purpose of the Study:
- To investigate the preventive role of male sex hormones against organ culture-induced vascular damage in rat aorta.
- To analyze potential changes in vascular gross structure associated with androgenic loss and induced damage.
Main Methods:
- Utilized aortic arterial segments from intact and orchidectomized rats, both fresh and after 20-hour organ culture.
- Assessed prostanoid (TXA2, PGE2, PGF2α, PGI2) release and vasomotor effects.
- Evaluated acetylcholine (ACh)-induced vasodilation, prostanoid involvement (especially TXA2), and thromboxane/prostaglandin (TP) receptor activation effects.
Main Results:
- Organ culture increased prostanoid production and prostanoid-induced vasomotor responses.
- ACh-induced relaxation decreased with indomethacin but increased with furegrelate (TXA2 synthase inhibitor) more in orchidectomized rats.
- ACh-induced relaxation was diminished by U-46619 (TP receptor agonist) only in orchidectomized rat arteries; vascular structure integrity was preserved.
Conclusions:
- Male sex hormones exert a protective effect against induced vascular damage.
- Androgens mitigate the deleterious impact of prostanoids, specifically TXA2, on vascular function.
- The findings support a role for androgens in maintaining vascular health and preventing damage.
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