Arteriolar reactivity of endotoxin-tolerant rats after hemorrhage and reinfusion.
Adrenergic and endothelium-dependent arteriolar reactivity are greatly reduced in hemorrhagic shock. However, development of tolerance to endotoxin may prevent the decrease. The reactivity of cremaster muscle arterioles was tested in pentobarbital-anesthetized endotoxin-tolerant (ENDT-T) and nontolerant control rats. Tolerance was developed by sublethal intraperitoneal injections of Escherichia coli endotoxin for 4 days (n = 9). Controls received saline (n = 9). Mean arterial pressure (MAP), arteriolar diameter-response curves to topical norepinephrine (NE) (10-9M to 10-3M) and responses to 10-3M acetylcholine (ACh) were obtained as follows 1) at control, 2) following hemorrhage to 40 mmHg. 3) after uptake of 25% of bled volume with the remainder infused, and 4) at 240 min post-hemorrhage. The A1, A2, and A3 arterioles were constricted following hemorrhage in the ENDT-T group and in the saline group. After reinfusion and in late shock, vessel diameters remained constricted. MAP increased to control levels (106 +/- 5 and 101 +/- 4 mmHg, respectively) following re-infusion in both groups but in late shock it decreased until death in the nontolerant group and decreased only minimally (96 +/- 4 mmHg) in the ENDT-T group. The nontolerant group NE ED50 increased from pre-hemorrhage to late shock (p < .05). The ENDT-T group ED50 was unchanged. The bleeding volumes of the two groups were not different. The survival time of the nontolerant group was 234 +/- 36 min, whereas the ENDT-T group all survived and were sacrificed at 427 +/- 30 min. The response to endothelium-dependent ACH vasodilation in late shock was significantly reduced in the saline group but was unchanged in the ENDT-T group. Alpha 1 receptor activity was maintained in both groups. Alpha 2 receptor activity was attenuated pre-hemorrhage and at 240 min post-hemorrhage in ENDT-T rats. In late shock, alpha 2 receptor activity was attenuated in nontolerant rats. The development of endotoxin tolerance prevents the loss of arteriolar responsiveness to NE and ACh. ENDT-T rats have attenuated alpha 2 receptor activity but not alpha 1 receptor activity.
Baker
C H
CH
Department of Physiology & Biophysics, College of Medicine, University of South Florida, Tampa 33612, USA.
Sutton
E T
ET
Price
J M
JM
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006439:Hemodynamics; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000503:physiopathology*
D008070:Lipopolysaccharides; D000109:Acetylcholine; D009638:Norepinephrine