Prolonged Regional Vasoconstriction Produced by NG-Nitro-L-Arginine in Conscious Sheep

Nitric oxide (NO) is a potent endothelium-derived vasodilator whose synthesis can be blocked both in vitro and in vivo by structural analogues of its precursor, L-arginine (L-ARG). We examined the dose-response profile of one such analogue, NG-nitro-L-arginine (NOLA) in conscious sheep (n = 4) and used continuous monitoring techniques to study long-term changes in mean arterial pressure (MAP), heart rate (HR), and cardiac output (CO) and the relative responsiveness of the coronary, mesenteric, renal, and hindlimb vascular beds to NOLA [10 mg/kg, intravenous (i.v.) bolus] in 5 sheep. NOLA (3 and 10 mg/kg) increased MAP at 1 h from 73 +/- 4 to 86 +/- 3 mm Hg (p < 0.05) and 73 +/- 1 to 106 +/- 8 mm Hg (p < 0.05), respectively. CO and HR decreased significantly after 10 mg/kg NOLA. Plasma endothelin (ET) level was unchanged after all doses of NOLA. Continuous monitoring of MAP, CO, and blood flow for 24 h before and after NOLA injection showed that MAP increased rapidly owing to a decrease in total peripheral conductance (TPC), with short-term reflex decreases in HR and prolonged decreases in CO and stroke volume (SV). Coronary and iliac conductances changed comparatively little. Renal conductance decreased by 43% at 80 min, but was not different from control after 6 h. The greatest and most sustained decrease in conductance, by a maximum of 55% of control levels at 110 min, occurred in the mesenteric bed.(ABSTRACT TRUNCATED AT 250 WORDS)