The question was addressed whether short-term (4 hour) NO deficiency, inducing an increase in blood pressure in anaesthetized dogs, does influence proteosynthesis in the myocardium and coronary arteries. A potentially positive answer was to be followed by the study of the supporting role of ornithine decarboxylase for the polyamines pathway. NG-nitro-L-arginine-methyl ester (L-NAME) (50 mg/kg per hour) was administered i.v. to inhibit NO synthase. After the first L-NAME dose diastolic blood pressure increased from 131.8 ±2.0 to 149.4 ±3.9 mm Hg (p< 0.001) and was maintained at about this level till the end of the experiment. Systolic blood pressure only increased after the first dose (from 150.8 ±1.1 to 175.0 ±5.8 mm Hg, p<0.01), returning thereafter to the control level. Similarly, the heart rate declined only after the first dose (from 190.4±5.3 to 147.6±4.5 beats/min, p<0.01). Total RNA concentrations increased in the left cardiac ventricle (LV), the left anterior descending coronary artery (LADCA) and left circumflex coronary artery (LCCA) by 15.9 ±0.7, 29.7 ±1.3 and 17.6 ±1.0%, p<0.05, respectively. The same applied to [14C]leucine incorporation (by 86.5 ±5.0, 33.5 ±2.6, 29.3±4.1 %, p<0.05, respectively). The above parameters indicated an increase of proteosynthesis in the LV myocardium and both coronary arteries LADCA and LCCA after short-term NO deficiency. Surprisingly, the ornithine decarboxylase activity in the LV myocardium decreased significantly by 40.2± 1.6 % (p<0.01) but the changes were not significant in the coronary arteries. This unexpected finding makes the role of polyamines in increasing proteosynthesis during a pressure overload due to NO deficiency questionable.
Nitric oxide concentration in the periendothelial area of the femoral vein in anaesthetized dogs was measured directly with a catheter- protected porphyrinic sensor. A 2- to 4-fold increase occurred in the basal NO concentration of 90±12 nM after acetylcholine injection (1-1.5 ,wg/kg). A linear correlation was found between femoral artery blood flow and NO concentration in the periendothelial area of the femoral vein. Noradrenaline decreased NO levels below the detection limit of the porphyrinic sensor (10 nM).
• NO concentration was measured in the periendothelial area of the femoral artery by Malinski’s porphyrinic • NO sensor in seven anaesthetized dogs. The basal concentration was 154.2 ±5.6 nM and two-minute intraarterial infusions of acetylcholine (3-4 /tg/ml/min) or bradykinin (30 - 40 ng/ml/min) increased this value significantly to 204.3±16.4 and 266.5±16.4 nM (P<0.01), respectively. Inhibition of »NO synthase by L-NAME (50 mg/kg) declined the basal • NO concentration only to 137.2±3.3 nM (PcO.Ol). Subsequent administration of acetylcholine and bradykinin attenuated significantly the increase in • NO concentration. Surprisingly, both agonists still induced a significant increase of *NO concentration by 125.3±8.3 and 156.6±26.9 nM, respectively (PcO.Ol). One of the possible explanations may be that besides arginine-citrulline plus the • NO pathway other sources of • NO could be involved in the high level of • NO after • NO synthase blockade by L-NAME.