Effect of electroacupuncture on response to immobilization stress.

Forced immobilization is a simple and effective stressor which produces large increases in heart rate (HR), blood pressure (BP), and plasma levels of norepinephrine (NE) and epinephrine (EPI). This study investigated the effects of electroacupuncture on BP, HR, and plasma catecholamine levels in rats challenged with immobilization stress. Male Sprague-Dawley rats received electroacupuncture (3 Hz, 0.2 ms pulses, 20 mA) for 30 min after start of immobilization stress (180 min). Needlepoints corresponded to Shaohai (HT3) and Neiguan (PC6) on the heart and pericardium channel. BP and HR were monitored with an indwelling carotid catheter, and blood samples were taken from the jugular vein. Blood (for HPLC determination of NE and EPI), mean BP, and HR were sampled at rest and during the immobilization stress at 15, 30, 60, 90, 120, 150, and 180 min. Electroacupuncture at HT3 and PC6 points but not at control points (TE5, LI11, and tail) significantly reduced the expected increases in BP, HR, and attenuated plasma levels of NE and EPI in response to 3 h of immobilization stress. Results provide strong evidence that electroacupuncture effectively reduces BP and HR increases and plasma catecholamine increases in rats challenged with immobilization stress.

Influence of 4-week and 8-week exercise training on the pharmacokinetics and pharmacodynamics of intravenous and oral azosemide in rats.

Cytochrome P450 expression was determined in the livers of control, 4-week exercised (4WE) and 8-week exercised (8WE) rats. Even though the 4-week and 8-week exercise training caused 53 and 25% increases, respectively, in total cytochrome P450 contents in the liver, exercise training did not cause any changes in the levels of P450 1A2 (which primarily metabolizes azosemide), 2E1 and 3A23 in the liver, as assessed by both Western and Northern blot analyses. Also, exercise training failed to alter the activity of NADPH-dependent cytochrome P450 reductase. The plasma concentrations of norepinephrine and epinephrine were significantly (2 to 3 folds) higher in 4WE rats than in controls, presumably due to physical stress, but the catecholamine levels in 8 WE rats returned to control levels. After intravenous administration (10 mg/kg of azosemide), the amount of unchanged azosemide excreted in 8-h urine (Ae(Azo, 0-8 h)) was significantly greater (46% increase) in 4WE rats than that in control rats. This resulted in a significantly faster (82% increase) renal clearance of azosemide. However, the nonrenal clearances were not significantly different between control and 4WE rats. The significantly greater Ae(Azo, 0-8 h) in 4WE rats was mainly due to a significant increase in intrinsic active secretion of azosemide in renal tubules and not due to a decrease in the metabolism of azosemide. After oral administration (20 mg/kg), Ae(Azo, 0-8 h) was also significantly greater (264%) in 4WE rats and this again was due to a significant increase in intrinsic active renal secretion of azosemide and not due to an increase in gastrointestinal absorption. After both intravenous and oral administration, the 8-h urine output was not significantly different between control and 4WE rats although Ae(Azo, 0-8 h) increased significantly in 4WE rats. This could be due to the fact that the urine output reached a plateau at 10 mg/kg after intravenous administration and 20 mg/kg after oral administration of azosemide to rats and possibly due to increase in plasma antidiuretic hormone levels and aldosterone production in 4WE rats.