Hemorrhage-induced Vascular Hyporeactivity to Norepinephrine in Select Vasculatures of Rats and the Roles of Nitric Oxide and Endothelin
Abstract
Hemorrhage-induced vascular hyporeactivity to norepinephrine (NE) and the possible effector roles of nitric oxide (NO) and endothelin (ET) were investigated in different vascular beds of rats. Under urethane anesthesia, rats (n= 7 per group) were hemorrhaged to a mean arterial pressure (MAP) of 50 mm Hgf or 60 min. A group of rats was pretreated with either NG-nitro-L-arginine methyl ester (10 mg/kg), an NO synthase inhibitor, or PD142893 (0.1 mg/kg), an ET receptor antagonist 15 min before the end of the hypotensive period. Operated, euvolemic rats served as controls. The responses of MAP and the blood flow of the superior mesenteric (SMA), celiac (CA), left renal (LRA), and left femoral arteries (LFA) to NE (3 g/kg, i.v.) were measured at baseline (prehemorrhage), at the end of the hypotensive period (0 h), and at 1, 2, and 4 h after the end of the hypotensive period. The pressor responses to NE on MAP at 0, 1, 2, and 4 h in the 60-min hemorrhage groups were reduced to 45.9%, 37.8%, 29.2%, 18.4 % of baseline pressor response, respectively. At these same times, the fall in blood flow in response to NE in SMA, CA, LRA, and LFA was significantly blunted ( P less than 0.01). This loss of responsiveness in CA and LFA was more severe than in SMA and LRA ( P less than 0.05- P less than 0.01). Pretreatment with L-NAME or PD142893 significantly improved the pressor response of MAP and the blood flow responses of the four arteries to NE (P less than 0.01). Hypotension at 50 mm Hg for 60 min resulted in an apparent loss of vascular reactivity to NE, and the four vasculatures studies were not affected to the same extent. In addition, NO and ET appear to contribute to the loss of vascular reactivity in different vasculatures in hemorrhagic shock.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2003
- Accession Number
- ADA628289
Entities
People
- John A. Ward
- Liang-ming Liu
- Michael A. Dubick
Organizations
- United States Army Institute of Surgical Research