Differential effects of chronic intermittent versus continuous hypoxia on cardiovascular function and skeletal muscle resistance arteries

Abstract

Exposure of rats to intermittent hypoxia for 8–12 hrs/day for several wks causes increased arterial pressure that is evident not only during exposure but throughout the 24-hr period. This increase is accompanied by impaired vasodilator function in skeletal muscle resistance arteries. We evaluated whether an intermittent pattern of hypoxic exposure is required to cause these vascular alterations by comparing responses to intermittent (IH) and continuous (CH) hypoxia. Sprague-Dawley rats were exposed to IH (10% FIO2 for 1–2 min at 4 min intervals; 12 hrs/day) or CH (12% FIO2; 24 hrs/day). Control rats were housed under normoxic conditions. After 14 days, gracilis arteries were isolated and cannulated with glass micropipettes, perfused and superfused with physiological salt solution which was equilibrated with 21% O2 and 5% CO2. Arteries were pressurized to 80 mmHg and diameters were measured using videomicroscopy before and after exposure to acetylcholine (ACH; 10−6M) or sodium nitroprusside (SNP; 10−4 M) in the superfusate. Arterial pressure was raised to the same extent (+10–15 mmHg) by IH and CH; however, CH caused a much larger increase in heart rate (+90 vs. +30 beats/min). Both IH and CH resulted in impaired ACH-induced vasodilation. The vasodilator response to SNP, which was not altered by IH, was greatly attenuated by CH. Thus, despite nearly identical effects on arterial pressure, 2 wks of IH and CH produced dissimilar patterns of vascular dysfunction in skeletal muscle resistance arteries. Funded by NIH #HL074072.