Abstract 087: Impaired Brain Cystathionine Beta-Synthase-Derived H ₂ S Production is Associated With the Development of Neurogenic Hypertension

Hydrogen sulfide (H 2 S) is recognized as an important physiological signaling molecule for cardiovascular homeostasis. Decreased circulating H 2 S levels are associated with the development of hypertension, and central administration of H 2 S donors reduces blood pressure in animal models. Cystathionine β-synthase (CBS), one of the H 2 S producing enzymes, is highly expressed in the brain. However, little is known about the role of CBS and brain endogenous H 2 S in the regulation of blood pressure. We hypothesized that impaired brain H 2 S production is associated with the development of neurogenic hypertension. In the 1 st experiment, male C57/BL6/J mice (10-12 wks, n=7) were infused with Angiotensin-II (Ang-II, 600 ng/kg/min, sc, mini-osmotic pump; neurogenic hypertension model) or saline for 4 weeks. Plasma and brain H 2 S levels were measured using gas chromatography-chemiluminesence. Following 4 wks of Ang-II infusion, mean arterial blood pressure (MAP) under anesthesia (carotid artery catheter) was significantly higher in Ang-II compared to saline-infused mice (108.5 ± 8 vs. 77.1 ± 1 mmHg, p < 0.01), confirming hypertension in the Ang-II group. Although plasma free H 2 S levels were not different between groups, brain free H 2 S level was significantly decreased in Ang-II-infused mice (3.3 ± 0.3 vs. 4.5 ± 0.4 pmol/mg, p < 0.05), suggesting that brain H 2 S production is impaired during neurogenic hypertension. In the 2 nd experiment, Neuron-specific CBS knockout mice (NS-CBS KO) and CBS Flox controls (male, 10-12 wks, n=6) were implanted with telemetry probes for conscious blood pressure recording. Ang-II was infused after baseline recording. The basal level of MAP was not different between NS-CBSKO and CBS Flox mice (96.5 ± 3 vs. 99.3 ± 4 mmHg, p < 0.05). After 1 wk of Ang-II infusion, MAP was significantly higher in NS-CBS KO compared to CBS Flox mice (126.6 ± 10 vs. 106.8 ± 5 mmHg, p < 0.05). Taken together, these data suggest that CBS is involved in the central regulation of blood pressure, and impaired brain CBS-derived H 2 S production promotes the development of neurogenic hypertension. (Funding: NIH R01 HL146098-01; NIGMS P30GM106392)