PROLONGED REGIONAL VASOCONSTRICTION PRODUCED BY N-G-NITRO-L-ARGININE IN CONSCIOUS SHEEP

Nitric oxide (NO) is a potent endothelium-derived vasodilator whose sy nthesis can be blocked both in vitro and in vivo by structural analogu es of its precursor, L-arginine (L-ARG). We examined the dose-response profile of one such analogue, N-G-nitro-L-arginine (NOLA) in consciou s sheep (n = 4) and used continuous monitoring techniques to study lon g-term changes in mean arterial pressure (MAP), heart rate (HR), and c ardiac output (CO) and the relative responsiveness of the coronary, me senteric, renal, and hindlimb vascular beds to NOLA [10 mg/kg, intrave nous (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 a fter 10 mgikg NOLA. Plasma endothelin (ET) level was unchanged after a ll doses of NOLA. Continuous monitoring of MAP, CO, and blood flow for 24 h before and after NOLA injection showed that MAP increased rapidl y owing to a decrease in total peripheral conductance (TPC), with shor t-term reflex decreases in HR and prolonged decreases in CO and stroke volume (SV). Coronary and iliac conductances changed comparatively li ttle. Penal conductance decreased by 43% at 80 min, but was not differ ent from control after 6 h. The greatest and most sustained decrease i n conductance, by a maximum of 55% of control levels at 110 min, occur red in the mesenteric bed. The degree and duration of the response to NOLA suggest that the NO system plays a major role in control of regio nal blood flow (RBF), with individual vascular beds exhibiting differe nt patterns of response over time.-