Different effects of naproxen on the organ blood flows in normo- and hypervolemic anaesthetized rats

The effects of naproxen, an inhibitor of the enzyme cyclooxigenase (10 mg/kg i.v.) on the distribution of the cardiac output (CO) and on the intrarenal hemodynamics were investigated in normovolemic (free salt and water uptake till the beginning of experiment) and hypervolemic (with i.v. infusion of 50 ml 0.9% NaCl solution/kg/10 min) narcotized rats. The cardiac output was measured on the basis of he Stewart-Hamilton principle, the blood flow of the organs by the Sapirstein method. 86Rb was used as indicator. In hypervolemia, the blood pressure is the same, the cardiac output is higher (CO-normovolemia: 23.1 +/- 7.04, CO-hypervolemia: 29.0 +/- 6.43 ml/min/100 g; p < 0.05) the total peripheral resistance (TPR) is lower (TPR-normovolemia: 40.0 +/- 9.39 R, TPR-hypervolemia: 31.2 +/- 8.34 R, p < 0.05) than in normovolemic animals. In hypervolemia the vascular resistance of the investigated organs (heart, lungs, kidney, skin, muscle, liver, spleen, intestine) is also lower and the intrarenal blood flow shifts toward the medulla. One hour following the naproxen administration a) in normovolemia joining to a slightly decreased cardiac output and increased TPR, the vascular resistance of the skin (R-control: 85.1 +/- 32.7, R-naproxen: 161 +/- 57.4; p < 0.001) and of the skeletal muscle (R-control: 114 +/- 35.1, R-naproxen: 190 +/- 81.9; p < 0.01) increases. The blood flow of the other organs and the intrarenal hemodynamics does not change under the effect of naproxen. b) in hypervolemia the general circulatory parameters (blood pressure, cardiac output, TPR) and the parameters of the organ circulation and intrarenal hemodynamics remain unchanged. The results suggest that in rats the prostanoid compounds (PGE2, PGI2, TXA2) a) can modify the blood flow of the skin and muscle in normovolemic animals, but they do not have any role in determining the blood flow of the other organs or the intrarenal distribution of blood flow. b) in hypervolemia they play no role in determining organ-, or intrarenal blood flow. The consequences of cyclooxygenaze enzyme inhibition--at least in the case of the organ blood flow--depend on the magnitude of sodium and water load in the organism.