n-255 Inhibition of Nitric Oxide, Bradykinin, and Prostaglandins in Normal Rats

We assessed the vasodilator effect of endothelium-derived nitric oxide by inhibiting its formation with JVG-monomethyl L-arginine (LNMMA) on systemic and regional hemodynamics in conscious, normotensive rats, using the radioactive microsphere technique. In rats injected with 10 mg/kg LNMMA (n=8), mean blood pressure increased by 16.2±2.6 mm Hg, and heart rate decreased by 543 ±16.7 beats per minute. In comparison with rats injected with 5% dextrose (n=14), cardiac index was lower by 35.6 % (/?<0.01), and total peripheral vascular resistance was higher by 51.6 % (p<0.01); regional blood flows were lower and vascular resistance higher in most organs. Changes were significant in the heart, kidney, stomach, large intestine, skin, and adrenals (/?<0.05). Preinjection of 100 mg/kg L-arginine prevented the pressor response but only partially attenuated the other hemodynamic effects of LNMMA. Combination of LNMMA with the bradykinin antagonist (D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg)trifluoroacetic acid (50 jtg/min for 5 minutes) did not produce systemic or regional effects different from those obtained with LNMMA alone. Combination of LNMMA with indomethacin (10 mg/kg) resulted in additional changes in the cerebral circulation, blood flow decreasing by an additional 44.2 % (p<0.01) and vascular resistance increasing by 753