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 Hg for 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 microg/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 < 0.01). This loss of responsiveness in CA and LFA was more severe than in SMA and LRA (P < 0.05-P < 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 < 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.

Androstenediol inhibits the trauma-hemorrhage-induced increase in caspase-3 by downregulating the inducible nitric oxide synthase pathway

“…It is evident that maintenance of liver circulation after hemorrhagic shock is critical in limiting liver injury (49,57). The maintenance of liver circulation relies partly on endothelin-1 and nitric oxide (NO) (2,27,37,43,58). However, an increased inducible NO synthase (iNOS) in hemorrhaged liver has been reported (8,11,23,43,47,48).…”

Hemodynamic responses and serum nitrite concentration during uncontrolled hemorrhagic shock in normotensive and hypertensive rats

“…Several circulating factors such as NO are involved in modulation of cardiovascular response to hemorrhagic shock 7 . Excessive formation of NO may contribute to pathogenesis of various shock and vascular hyporeactivity in various shocks 7,16,17 . In the present study, serum nitrite level in HT animals was lower than NT group which may be the result of endothelial dysfunction in these animals 18,19 .…”

Stimulation of the adenosine A3 receptor reverses vascular hyporeactivity after hemorrhagic shock in rats

“…Therefore, we hypothesized that A 3 AR might be involved in the modulation of vasoreactivity through a RyR-mediated Ca 2+ release and BK Ca channel dependent signal pathway after hemorrhagic shock. In this study, we examined: (1) whether A 3 AR is involved in the modulation of vascular reactivity after hemorrhagic shock in rats and (2) whether A 3 AR modulates the vascular reactivity to NE after hemorrhagic shock through a RyR-mediated Ca 2+ release-dependent pathway. To the best of our knowledge, this is the first report to demonstrate that A 3 AR is involved in the modulation of vasoreactivity after hemorrhagic shock and that stimulation of A 3 AR could restore the decreased vasoreactivity to NE through a RyR-mediated, BK Ca channel dependent signal pathway.…”