Transcapillary transport of solutes in the myocardium: effects of nitroglycerin, isoproterenol and histamine on permeability-surface area products of inulin and sucrose.
Three vasoactive drugs (nitroglycerin, isoproterenol and histamine) were examined for their effects on microsolute transport across capillary walls in the myocardium. Coronary arteries of the isolated rabbit heart were perfused at constant pressure with Tris-buffered Ringer's solution (pH = 7.4, 37 degrees C) with and without drug present in the perfusion fluid. A mixture of [3H]inulin and [14C]sucrose was injected into the left ventricular wall. From measured clearance rates, capillary permeability-surface area products (PS) (in milliliters per minute per 100 g) were computed for both solutes by the method of Gosselin and Stibitz (Pflügers Arch. 318: 85-98, 1970). Mean control PS values were 60.7 and 14.1 for sucrose and inulin, respectively. This computation required experimental determination of the myocardial volume of distribution (in milliliters per gram) for each reference solute. Values of myocardial volume of distribution obtained in the presence of nitroglycerin, isoproterenol and histamine did not differ significantly from controls. In paired clearance trials, isoproterenol and nitroglycerin significantly increased coronary flow, but neither drug influenced PS-inulin, PS-sucrose or the ratio PS inulin/PS sucrose. In contrast, histamine caused an apparently irreversible decrease in flow. Furthermore, in the presence of histamine, PS inulin/PS sucrose increased from 0.28 +/- 0.03 to 0.40 +/- 0.05 (P less than 0.003). This rise is consonant with a widening of diffusion channels between neighboring endothelial cells in the capillary wall. Thus, histamine (and presumably substances capable of histamine release) appears to increase myocardial permeability to microsolutes, in addition to its well known ability to enhance protein transport across postcapillary venules.
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D005260:Female; D006321:Heart / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007444:Inulin / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate; D009206:Myocardium / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology*; D011817:Rabbits; D013395:Sucrose / Q000378:metabolism*
D013395:Sucrose; D006632:Histamine; D007444:Inulin; D005996:Nitroglycerin; D007545:Isoproterenol