Gonadal function protects against organ culture-induced vascular damage. Involvement of prostanoids

Diva M Villalpando; Juan Gómez Rivas; Daniel Flynn; Fermín R de Bethencourt; Mercedes Ferrer

doi:10.1016/j.prostaglandins.2019.106406

Gonadal function protects against organ culture-induced vascular damage. Involvement of prostanoids

Prostaglandins Other Lipid Mediat. 2020 Jun:148:106406. doi: 10.1016/j.prostaglandins.2019.106406. Epub 2020 Jan 13.

Authors

Diva M Villalpando¹, Juan Gómez Rivas², Daniel Flynn¹, Fermín R de Bethencourt², Mercedes Ferrer³

Affiliations

¹ Departamento de Fisiología, Facultad de Medicina, UAM, Spain.
² Servicio de Urología, Hospital Universitario La Paz, Madrid, Spain; Instituto de Investigación Hospital Universitario La Paz (IdiPAZ) Madrid, Spain.
³ Departamento de Fisiología, Facultad de Medicina, UAM, Spain; Instituto de Investigación Hospital Universitario La Paz (IdiPAZ) Madrid, Spain. Electronic address: mercedes.ferrer@uam.es.

PMID: 31945460
DOI: 10.1016/j.prostaglandins.2019.106406

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, PGF_2α 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.

Keywords: Androgens; Gonadal function; Organ culture; Prostanoids; Rat aorta; TXA(2); Vascular structure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Androgens / pharmacology*
Animals
Aorta / drug effects*
Aorta / metabolism
Aorta / pathology
Blood Pressure
Cyclooxygenase 2 / chemistry
Endothelium, Vascular / drug effects*
Endothelium, Vascular / metabolism
Endothelium, Vascular / pathology
Male
Models, Animal
Orchiectomy / methods*
Organ Culture Techniques / methods*
Prostaglandins / toxicity*
Rats
Rats, Sprague-Dawley
Thromboxane A2 / toxicity*
Thromboxane-A Synthase / antagonists & inhibitors

Substances

Androgens
Prostaglandins
Thromboxane A2
Cyclooxygenase 2
Thromboxane-A Synthase