Qabazard Bedoor, Yousif Mariam H M, Phillips Oludotun A
Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait City, Kuwait.
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
Int J Impot Res. 2019 Mar;31(2):111-118. doi: 10.1038/s41443-018-0083-x. Epub 2018 Oct 9.
GYY4137 is a novel hydrogen sulfide (HS) releasing molecule with vasodilator activity. The objectives of this study were to investigate: (1) the pharmacological effect of GYY4137 on the reactivity of the corpus cavernosum (CC) from normal and diabetic rats; (2) the contribution of ATP-sensitive potassium (K-ATP) channels and nitric oxide (NO) pathway; (3) the reactivity to vasoactive agonists following ex vivo incubation of the diabetic rat CC with GYY4137. Longitudinal strips of CC from control and diabetic male Sprague-Dawley (SD) rats (n = 5-6 animals per group) were suspended in organ-baths. Responses to GYY4137, carbachol, or phenylephrine (PE) were determined by measurement of changes in isometric tension. The effects of acute incubation of the CC strips with L-NAME (NO synthase inhibitor) or glibenclamide (K-ATP channel inhibitor) on the relaxant responses to GYY4137 were examined. The effect of ex vivo incubation with GYY4137 (10 M) on the responses of CC to carbachol or PE was evaluated. We found that GYY4137 provoked relaxation in the CC strips, which was significantly reduced in the presence of L-NAME or glibenclamide. Ex vivo incubation of diabetic CC with GYY4137 resulted in a significant improvement in the vascular responses to the added agonists. We conclude that GYY4137 is a relaxant agonist in SD rats CC, and the response is mediated, at least in part, by NO and K-ATP channels. Brief incubation of diabetic CC with GYY4137 markedly improved the impaired vascular reactivity, thus raising the question whether chronic in vivo treatment of diabetic animals with GYY4137 would have any protective effect, which is worth further investigation.
GYY4137是一种具有血管舒张活性的新型硫化氢（HS）释放分子。本研究的目的是探讨：（1）GYY4137对正常和糖尿病大鼠海绵体（CC）反应性的药理作用；（2）ATP敏感性钾（K-ATP）通道和一氧化氮（NO）途径的作用；（3）糖尿病大鼠CC与GYY4137离体孵育后对血管活性激动剂的反应性。将对照和糖尿病雄性Sprague-Dawley（SD）大鼠（每组n = 5 - 6只动物）的CC纵向条带悬挂在器官浴槽中。通过测量等长张力的变化来确定对GYY4137、卡巴胆碱或去氧肾上腺素（PE）的反应。研究了CC条带与L-NAME（NO合酶抑制剂）或格列本脲（K-ATP通道抑制剂）急性孵育对GYY4137舒张反应的影响。评估了GYY4137（10 μM）离体孵育对CC对卡巴胆碱或PE反应的影响。我们发现GYY4137可引起CC条带舒张，在L-NAME或格列本脲存在时显著减弱。糖尿病CC与GYY4137离体孵育导致对添加激动剂的血管反应显著改善。我们得出结论，GYY4137是SD大鼠CC中的一种舒张激动剂，其反应至少部分由NO和K-ATP通道介导。糖尿病CC与GYY4137短暂孵育可显著改善受损的血管反应性，因此引发了一个问题，即GYY4137对糖尿病动物进行慢性体内治疗是否会有任何保护作用，这值得进一步研究。
