PROTECTIVE ROLE OF NO IN THE REGIONAL HEMODYNAMIC-CHANGES DURING ACUTE ENDOTOXEMIA IN RATS

The role of NO during the first hour of endotoxemia is still controver sial. To evaluate whether NO is protective or detrimental to the regul ation of systemic blood pressure, cardiac output (CO), and organ perfu sion in rats during acute endotoxemia, we have studied the effects of inhibition of NO synthesis. Thirty minutes after 0.1 mg N-G-nitro-L-ar ginine (L-NNA; group L, n = 7, partial inhibition), 1 mg L-NNA (group H, n = 6, complete inhibition), or saline (group E, n = 7) intravenous infusion, anesthetized volume-loaded rats were infused with endotoxin Escherichia coli O127:B8 (8 mg.kg(-1) h(-1)) from time (t) = 0 to 60 min. Organ blood flow was measured with radioactive microspheres. In g roup H, at time 0, CO was lower than in group E (by -29%; P < 0.05), a nd systemic vascular resistance (SVR) was higher than in groups E and L (by 72 and 51%, respectively; P < 0.05). Perfusion of the pancreas, stomach, intestines, and kidney was lower (P < 0.05) and corresponding organ vascular resistance (OVR) higher (P < 0.05) in group H than in groups E and L (except kidney in group L). At t = 60 min, in groups H and L, CO was lower (by -45 and -26%, respectively; P < 0.05) and SVR was higher (by 112 and 54%, respectively; P < 0.05) than in group E. I n group L only blood flow to the heart, pancreas, intestines, and kidn ey was significantly lower than in group E, and corresponding OVR was higher. In group H perfusion of all organs (except spleen) was lower ( P < 0.05) and OVR in the heart, pancreas, stomach, intestines, kidney, and skin was higher (P < 0.05) than in group E. Complete, and even pa rtial, inhibition of NO synthesis thus had adverse effects in our endo toxin model: NO synthesis prevented severe hypoperfusion of especially the pancreas, small and large intestines, and kidney.