In the present study the effects of thyrotropin releasing hormone (TRH) and its stable analogue, CG3703, on cardiac output (thermodilution, Cardiomax) and regional blood flow (BF; directional pulsed Doppler technique) were investigated in hypovolemic hypotension in the rat. In urethan-anesthetized rats TRH (0.5 or 2 mg/kg ia) or CG3703 (0.05 or 0.5 mg/kg ia) reversed the bleeding (27% of the blood volume)-induced decreases in mean arterial pressure (MAP) and cardiac index (CI) and increased the heart rate (HR) and total peripheral resistance index (TPRI) in a dose-related manner. In the conscious rat exposed to a 45% hemorrhage, CG3703 (0.5 mg/kg ia) significantly raised MAP, HR, and TPRI with maximum changes of +67 +/- 6 (SE) mmHg, +123 +/- 30 beats/min, and +101 +/- 2%, respectively, CG3703 (0.5 mg/kg ia) also further enhanced the hemorrhage-induced reduction of hindquarter, mesenteric, and renal BF. The changes in BF in saline-treated vs. CG3703-treated rats 2 h after the bleeding were -32 +/- 6 vs. -55 +/- 6% (P less than 0.001) in hindquarter, -9 +/- 8 vs. -61 +/- 11% (P less than 0.001) in mesenteric, and -2 +/- 9 vs. -33 +/- 9% (P less than 0.01) in the renal artery; the changes in vascular resistance +30 +/- 7 vs. +309 +/- 167% (P less than 0.001) in hindquarter, -4 +/- 8 vs. +349 +/- 244% in the mesenteric, and -10 +/- 9 vs. +80 +/- 10% (P less than 0.01) in the renal artery. The survival rate after the 45% hemorrhage was significantly reduced by both TRH and CG3703.(ABSTRACT TRUNCATED AT 250 WORDS)
Central ventilatory effects of thyrotropin-releasing hormone in the conscious rat