Involvement of NO and ROS in Organ Culture‐induced Vascular Damage. Influence of Androgenic Function

Abstract

Androgen deprivation may induce vascular dysfunction by altering the release and action of different factors, such as nitric oxide (NO) and reactive oxygen species (ROS), that maintained along the time lead to cardiovascular diseases. On the other hand, vascular damage can be induced by organ‐culture system, which has been reported as a valid model to study the phenotypic changes that occur in several cardiovascular pathologies. Since there are no studies analyzing the impact of androgenic loss on vascular vulnerability, the objective of this study was to analyze the preventive role of sex hormones on the vascular damage induced by organ‐cultured, as well as the involvement of NO and ROS on the acetylcholine‐ (ACh) induced relaxation. For this purpose, aortic segments from control and orchidectomized rats were incubated for 20 hours at 37°C in serum‐free culture medium, and the following parameters were studied: i) the release of NO and the expression of iNOS; ii) the production of hydrogen peroxide and the activity of peroxidase; iii) the vasodilator responses induced by acetylcholine (ACh), sodium nitroprusside (SNP), a NO donor, and 8Br‐cGMP, a cell‐permeable analog of cGMP; and iv) the effect of L‐NAME or Tempol (inhibitor of NOS or ROS scavenger, respectively) on the ACh‐induced response. The results showed that organ culture‐induced vascular damage increased NO release, iNOS expression and the production of hydrogen peroxide in similar extent in arteries from control or orchidectomized rats, while the increase in peroxidase activity was greater in arteries from orchidectomized than in those of control rats. Organ‐culture decreased the ACh‐induced response and did not modify the SNP‐ or 8Br‐cGMP‐induced responses in arteries from control rats, while enhanced the SNP‐induced response in arteries from orchidectomized rats. L‐NAME and Tempol decreased the ACh‐induced response in cultured arteries from orchidectomized rats, while that induced by SNP was increased. These results show that organ culture promotes oxidative stress and vascular inflammation in arteries from both control or orchidectomized rats in which the increased NO and hydrogen peroxide production are involved, although the action of theses mediators seems to be less in arteries from control rats. Overall, these results indicate that the androgenic function protects against organ cultured‐induced vascular damage by minimizing the effect of NO and ROS as well as the alteration in the endothelium‐dependent vasodilator response.Support or Funding InformationSupported from Comunidad de Madrid (S2013/ABI‐2783, “INSPIRA1‐CM”) and Fondo Europeo de Desarrollo Regional.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.