Chronic Intermittent Hypobaric Hypoxia (4600 M) Attenuates Pulmonary Vasodilation Induced by Acetylcholine or Sodium Nitroprusside.

ABSTRACT

Moraga, Fernando A., Giselle Miranda, Vasthi López, Carmen Vallejos, and Daniel Silva. Chronic intermittent hypobaric hypoxia (4600 M) attenuates pulmonary vasodilation induced by acetylcholine or sodium nitroprusside. High Alt Med Biol. 19149-155, 2018. BACKGROUND: Previous studies performed in rats exposed to chronic intermittent hypobaric hypoxia (CIHH), at a simulated altitude of 4600 m, showed reduced nitric oxide (NO) production, increased arginase activity, and increased oxidative stress. However, studies on vascular function are scarce. Our aim was to measure plasma nitrate and nitrite (NOx) concentration and study pulmonary vascular function in rats exposed to CIHH in the presence of potassium chloride (KCl), acetylcholine (Ach), and sodium nitroprusside (SNP). METHODS: Thirty male Wistar rats were divided into two groups A control group (normoxia (N), n = 10) and a CIHH group (2N × 2H × 30 days, n = 20). CIHH exposure was performed in a hypobaric chamber at 428 Torr (4600 m). Noninvasive systolic blood pressure (SBP), heart rate, and body weight (BW) were measured. Blood samples were obtained to measure NOx levels and hematocrit (Hct). CIHH animals that gained BW and presented a Hct <20% and maintained SBP were classified as tolerant, and animals that lost >30% of their BW, increased Hct and SBP >20% were classified as intolerant. Animals were sacrificed and small pulmonary arteries (SPA) were obtained to perform concentration-response curves to KCl, Ach, and SNP. RESULTS AND CONCLUSIONS: Intolerant rats (30%) had decreased NOx levels. SPA had a larger vasocontraction response to KCl and a lower dilation response to SNP in the SPA compared to tolerant and control animals. In addition, SPA had a lower dilatation response to Ach compared with the control. Together, these results show that CIHH alters endothelium-dependent vasodilation.