Heart rate-dependence of aortic pulse wave velocity in rats

Aortic pulse wave velocity (aPWV), a surrogate measure of arterial stiffness, is a strong independent predictor of cardiovascular disease and all-cause mortality. Whilst studies have shown associated changes in arterial stiffness with acute changes in heart rate (HR), the effect of HR on aPWV at different mean arterial pressures (MAPs) have not yet been fully investigated. In this study, aPWV was measured in age-matched (12 weeks), urethane-anaesthetized normotensive rats (n6) at different HRs across a wide MAP range (40–160 mmHg). HR changes were achieved by atrial pacing at randomly sequenced rates (350, 400 and 450 bpm) after the resting HR was lowered with multiple doses of a bradycardic agent (zatebradine, 1mg/kg, i.v.). MAP was increased and decreased by infusions of phenylephrine and sodium nitroprusside respectively (30 g/kg/min i.v.). Effects of HR on aPWV were analysed at each low (40–80 mmHg), medium (80–120 mmHg) and high (120–160 mmHg) MAP range. Data are presented as mean se and Student’s 2-tailed t-test for paired observations was applied to compare means of aPWV at two different HRs within the same MAP range. HR is shown to have no significant effects on aPWV at the low and medium MAP ranges, but a significant difference in mean aPWV was observed in the high MAP range between the lowest and highest HR. These findings indicate a HR-dependence of aPWV at high MAPs in rats. This is of particular interest as studies in humans have shown conflicting results of HR effects on arterial stiffness when blood pressure was relatively unchanged. These results suggest that the values of MAP and HR may also need to be accounted for when making comparisons across studies.