Cystathionine gamma lyase (CSE) deficiency promotes increased contraction of the corpus cavernosum

Cystathionine γ lyase (CSE) is the primary enzyme responsible for hydrogen sulfide (H 2 S) production in the vasculature. Although, it is known that H 2 S is a vasodilator systemically, little is known about the effect of CSE on the arteries and tissues responsible for erectile function. Adequate relaxation of the pre-penile arteries and corpus cavernosum are important for effective penile erection, while excessive contraction impedes erectile response. The aim of our study was to determine the effect of CSE deletion on pre-penile vessels and erectile tissue reactivity. We hypothesized that CSE deletion will impair vascular relaxation of these tissues. We used 12 CSE KO mice and 12 age matched controls for this study. The mice were fed with normal chow and water ad libitum and sacrificed at 1 year of age. The distal internal pudendal arteries (dIPA), internal iliac arteries (IIA) and corpus cavernosum (CC) were harvested and used for ex vivo functional assessment. Tissue and wire myography studies were carried out to assess adrenergic and endothelium-dependent vasoconstrictions using cumulative dose-responses to phenylephrine (PE), endothelin, U-46619 and electrical stimulation (E-stim). Endothelium-dependent relaxation was assessed by acetylcholine (ACh) and endothelium-independent relaxation was assessed using Sodium nitroprusside (SNP). Na 2 S was used to assess the vascular reactivity to H 2 S. Finally, Non-adrenergic non-cholinergic (NANC) transmission was assessed using E-stim; 20V of electrical impulses were delivered to the tissues with frequency ranging from 0.5 to 16Hz following the administration of atropine, guanethidine and pre-constriction with PE. There were no significant differences observed in the relaxation due to ACh, SNP or NANC-stimulation in any tissue type. However, we found that the loss of CSE increased the contraction of the CC in response to electrical stimulation (p=0.024) and U-46619 (p=0.030). These results indicate that chronic deficiency of CSE increases sensitivity to two prominent vasoconstriction pathways in the CC, which may result in increased vascular resistance in the penis rather than the arteries that supply blood to the penis. Chronic H 2 S deficiency may thus result in impaired erectile function. This work was supported in part by National Institute of Health grant R03DK131242 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.