TIME-COURSE OF CHANGES IN HEART-RATE AND BLOOD-PRESSURE VARIABILITY IN STREPTOZOTOCIN-INDUCED DIABETIC RATS TREATED WITH INSULIN

Autonomic neuropathy is a frequent complication of diabetes associated with higher morbidity and mortality in symptomatic patients, possibly because it affects autonomic regulation of the sinus node, reducing h eart rate (HR) variability which predisposes to fatal arrhythmias. We evaluated the time course of arterial pressure and HR and indirectly o f autonomic function (by evaluation of mean arterial pressure (MAP) va riability) in rats (164.5 +/- 1.7 g) 7, 14, 30 and 120 days after stre ptozotocin (STZ) injection, treated with insulin, using measurements o f arterial pressure, HR and MAP variability. HR variability was evalua ted by the standard deviation of RR intervals (SDNN) and root mean squ are of successive difference of RR intervals (RMSSD). MAP variability was evaluated by the standard deviation of the mean of MAP and by 4 in dices (P-1, P-2, P-3 and MN) derived from the three-dimensional return map constructed by plotting MAP, x [(MAP(n+1))-(MAP(n))] x density. T he indices represent the maximum concentration of points (P-1), the lo ngitudinal axis (P-2), and the transversal axis (P-3) and MN represent s P-1 x P-2 x P-3 x 10(-3). STZ induced increased urinary glucose in d iabetic (D) rats compared to controls (C). Seven days after STZ, diabe tes reduced resting HR from 380.6 +/- 12.9 to 319.2 +/- 19.8 bpm, incr eased HR variability, as demonstrated by increased SDNN, from 11.77 +/ - 1.67 to 19.87 +/- 2.60 ms, did not change MAP, and reduced P-1 from 61.0 +/- 5.3 to 51.5 +/- 1.8 arbitrary units (AU), P-2 from 41.3 +/- 0 .3 to 29.0 +/- 1.8 AU, and MN from 171.1 +/- 30.2 to 77.2 +/- 9.6 AU o f MAP. These indices, as well as HR and MAP, were similar for D and C animals 14, 30 and 120 days after STZ. Seven-day rats showed a negativ e correlation of urinary glucose with resting HR (r = -0.76, P = 0.03) as well as with the MN index (r = -0.83, P = 0.01). We conclude that rats with short-term diabetes mellitus induced by STZ presented modifi ed autonomic control of HR and MAP which was reversible. The metabolic control may influence these results, suggesting that insulin treatmen t and a better metabolic control in this model may modify arterial pre ssure, HR and MAP variability.