Abstract
Responses of the perfused forelimb paw small vein in anesthetized dog to vasoactive agents including serotonin, histamine, bradykinin, acetylcholine and epinephrine were investigated together with their modification by anti-inflammatory drugs. Venous perfusion with blood frequently caused venospasms which could not be attenuated by anesthetics, gallamine or phentolamine. In perfusion experiments both with blood and with Krebs-bicarbonate solution, close i.v. injections of epinephrine, serotonin and acetylcholine caused marked venoconstrictions (threshold doses in blood perfusion experiments, about 1, 3 and 300 ng, respectively), whereas bradykinin and histamine produced only weak constrictive responses even in large doses of more than 3 μg. Close i.v. injections of non-steroidal anti-inflammatory drugs, i.e. phenylbutazone, 150 μg/min, sodium salicylate, 500 μg/min, indomethacin, 50 μg/min, aminopyrine, 300 μg/min and benzydamine, 10 μg/min, nonspecifically depressed the venoconstrictor responses to epinephrine, serotonin, acetylcholine, bradykinin and histamine. A steroidal anti-inflammatory drug, hydrocortisone, however, tended to enhance the effect of epinephrine with no influence on the effects of the other vasoactive agents. The results suggest that the inhibitory effects of non-steroidal antiinflammatory drugs on the venoconstrictor responses to the vasoactive agents may contribute to their anti-inflammatory activity through the inhibition of facilitated vascular permeability due to the rise in hydrostatic pressure of the fine blood vessels.
