Role of nitric oxide synthase and cystathionine gamma-lyase in the effects of leptin and apelin on water intake in rats

Medical Review (Med. pregled), 2025, 61(2), 45-51.

M. Hristov, L. Lazarov, P. Gateva

Department of Pharmacology and Toxicology, Faculty of Medicine, Medical University of Sofia

Abstract. Introduction: Leptin and apelin are adipokines that play a key role in regulating various physiological functions. Nitric oxide and hydrogen sulfide are signaling molecules of critical importance for the control of water balance. Aim: This study aimed to investigate the effect of systemic intraperitoneal (i.p.) administration of leptin and the pyroglutamated apelin-13 ([Pyr1]apelin-13) on water intake in rats. Furthermore, we examined the hypothesis that inhibition of hydrogen sulfide synthesis by the cystathionine gammalyase inhibitor dl-propargylglycine or inhibition of nitric oxide synthesis by the non-selective nitric oxide synthase inhibitor l-NAME or the selective inducible nitric oxide synthase inhibitor aminoguanidine could modulate the effects of leptin and apelin on water consumption. Materials and methods: Rats were injected with L-NAME (50 mg/kg, i.p.), dl-propargylglycine (50 mg/kg, i.p.), aminoguanidine (50 mg/kg, i.p.), or saline, followed 10 minutes later by leptin (0.5 mg/kg, i.p.), [Pyr1] apelin-13 (0.5 mg/kg, i.p.), or saline. To measure water intake, the animals were individually housed in separate cages with access to water through graduated bottles. Water intake was recorded 24 hours after substance administration. Results: Leptin alone did not significantly affect water intake, whereas [Pyr1]apelin-13 significantly increased water consumption compared to the control group. Administration of l-NAME, aminoguanidine, or dl-propargylglycine alone did not significantly affect water intake. The combination of leptin with L-NAME reduced water consumption, whereas the combinations with aminoguanidine or dl-propargylglycine had no effect. Co-administration of [Pyr1]apelin-13 with L-NAME significantly suppressed apelin-induced increases in water intake. The combination of [Pyr1]apelin-13 with aminoguanidine did not affect the apelin-induced effect, while the combination with dl-propargylglycine abolished the apelin-induced increase in water consumption. Conclusion: These results provide valuable insights into the physiological roles of nitric oxide and hydrogen sulfide in the integration of leptin and apelin signaling. Further studies are needed to clarify the specific roles of different nitric oxide synthase isoforms and hydrogen sulfide-producing enzymes in these mechanisms.

Key words: leptin, apelin, nitric oxide, hydrogen sulfide, L-NAME, aminoguanidine, dl-propargylglycine, water intake

Address for correspondence: Milen Hristov, MD, PhD, e-mail: ; ;
ORCID ID: 0000-0002-6185-2157