Effects of intravenously infused histamine on canine forelimb transvascular protein efflux following adrenergic receptor blockade.

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The intravenous infusion of high doses of histamine (400 micrograms base/min) produced only small increases in weight (approximately equal to +30 g) and lymph total protein concentration (+ 0.9 g/100 ml) in canine forelimbs perfused at constant inflow. The weight gain was associated with profound decreases in aortic pressure (112 to 30 mm Hg) and in forelimb perfusion pressure (105 to 75 mm Hg) and marked increases in forelimb skin small-vein pressure (from 12 to 25 mm Hg). After treatment with phentolamine, the intravenous infusion of these doses of histamine under the same conditions produced marked decreases in forelimb perfusion pressure (120 to 60 mm Hg) and failed to increase forelimb skin small-vein pressure, yet still produced only minimal increases in weight (+ 12 g) and lymph total protein concentration (+ 0.8 g/100 ml). Following treatment with both phentolamine and propranolol, the intravenous infusion of histamine caused very marked increases in forelimb weight (approximately equal to +75 g) and lymph total protein concentration (+ 2.9 g/100 ml). These marked increases in forelimb weight and lymph formation were associated with profound decreases in perfusion pressure (112 to 60 mm Hg) but no change in skin small-vein pressure relative to control. These same increases in weight and lymph total protein concentration were observed after treatment with propranolol alone. Thus, treatment with propranolol markedly increased net fluid filtration and protein efflux during intravenous infusions of massive doses of histamine, idicating that this edemogenic agent causes an endogenous release of catecholamines which tend to antagonize the direct actions of histamine on the microvascular membrane via stimulation of beta-adrenergic receptors.