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Effects of Hydrogen Sulfide on Mesenteric Blood Flow
Author(s) -
Barrera Adelaeda,
Naik Jay,
Gonzalez Bosc Laura V.,
Mendiola Perenkita,
Kanagy Nancy L.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1012.21
Subject(s) - medicine , vascular resistance , saline , anesthesia , vasodilation , superior mesenteric artery , blood pressure , bolus (digestion) , hemodynamics
In sleep apnea, recurrent obstruction of the upper airway leads to sleep fragmentation and intermittent hypoxia (IH). In animal studies, IH causes wake‐time hypertension by elevating vascular resistance due in part to decreased production of the vasodilator, hydrogen sulfide (H 2 S). Inhibiting cystathionine γ‐lyase (CSE) to prevent H 2 S synthesis augments constriction in isolated mesenteric arteries, but H 2 S regulation of resistance in this vascular bed in vivo is unknown. The goal of this study was to evaluate CSE regulation of blood flow and resistance in the mesenteric circulation of control rats and in rats made hypertensive by exposure to IH for 14 days. We hypothesized that inhibiting CSE would increase vascular resistance and mean arterial pressure (MAP) more in control than in IH exposed rats. Rats were anesthetized with inhaled isofluorane (2%) and instrumented with femoral artery and vein catheters as well as Doppler flow probes on the main mesenteric artery. Under anesthesia, CSE inhibition (β‐cyanoalanine, BCA, 30mg/kg bolus + 5 mg/kg/min for 20 minute) increased MAP in both control and IH rats compared to saline infusion (control: 7.2±1.2 vs. −2.8±1.1; IH: 9.3±1.1 vs. 3.3±0.7, % change from baseline, p<0.05, n=6–8 rats per group) but did not alter mesenteric resistance. To determine if anesthesia masked acute changes in vascular resistance in response to CSE inhibition, the study was repeated in conscious animals. In conscious control rats, BCA infusion significantly increased MAP (saline −0.8±1.18 vs BCA 7.9±2.55, % change from baseline, p<0.05, n=7) and mesenteric resistance (saline 0.9±3.1 vs BCA 15.6±6.5, % change from baseline, p<0.05, n=12). We then tested our hypothesis that chronic CSE inhibition would increase vascular resistance and MAP in control but not in IH rats. The irreversible CSE inhibitor DL‐propargylglycine (PAG) was used to permit a once daily i.v injection (50 mg/kg/day for 5 days). CSE inhibition significantly increased both, MAP and mesenteric resistance in control but not in IH rats (MAP: control: 110.3±2.9 vs. 122.4±4.0 post PAG; IH: 118.8±2.1 vs. 111.3±3.7 post PAG, mmHg, p<0.05 n=3–5 rats per group; Relative mesenteric resistance normalized to starting values: Sham: 1±0 vs. 1.5±0.07.1; IH: 1±0 vs. 0.85±0.19, p<0.05, n=3–5 rats per group). Our results suggest that endogenous H 2 S is an important regulator of blood pressure and mesenteric vascular resistance and that this control is lost after IH exposure. Support or Funding Information This work was supported by the NIH, NHLBI, and AHA [Grants HL123301, HL007736‐21, and 15GRNT25090039 (LGB)] and institutional funding from the University of New Mexico.