Morphological and physiological correlation of bradykinin-induced macromolecular efflux

Abstract

Bradykinin applied topically for 4 min produced marked dose-related increases in the number of fluorescent dextran (mol wt 145,000) vascular leakage sites exclusively from small postcapillary venules--evidence for an increase in macromolecular permeability. The increase in macromolecular permeability was short-lived, making repeated applications possible. The number of bradykinin-induced venular fluorescent dextran leakage sites could be greatly reduced by the simultaneous topical application of isoproterenol, and this antagonism of the increase in macromolecular permeability could be prevented by pretreatment with propranolol. The topical application of papaverine failed to antagonize the increase in the number of venular leakage sites of fluorescent dextran by bradykinin. A continuous 90-min superfusion of bradykinin elicited an initial marked increase in the number of fluorescent dextran venular leakage sites, which then waned after 20-30 min, returning to near control despite the continued superfusion with bradykinin. In canine forelimbs the bradykinin-induced increase in protein efflux, total protein transport, and lymph flow also peaked in approximately 30 min and then waned markedly despite continued local intra-arterial infusions of this agent for prolonged periods. The morphological data from the cheek pouch agrees well with the physiological data from the forelimb, suggesting that an increase in protein efflux in the canine forelimb could be readily explained by an increase in the number of large pores.

Bradykinin Production and Increased Pulmonary Endothelial Permeability during Acute Respiratory Failure in Unanesthetized Sheep

“…The morphological evidence in the above studies suggested that this leakage may in part be mediated by BK induced endothelial cell contraction, hence increasing the size of intercellular gaps (30,31). BK may also increase permeability by increasing vesicular transport (16).…”

“…BK is a potent systemic arteriolar vasodilator and is edematogenic in bronchial vessels (30) and systemic tissues (16,31). We have recently shown that intravenous infusions of BK increase water and protein movement in the hypoxic lung (7).…”

“…Angiotensin II is a potent vasoconstrictor, whereas BK is a potent vasodilator. Catecholamines can oppose the permeability changes induced by histamine (39) or BK (31,40).…”

Role of protein kinase C in bradykinin-induced increases in microvascular permeability.

“…Morphological evidence suggests that bradykinin increases macromolecular efflux through the formation of intercellular gaps between endothelial cells23 that are located principally in postcapillary venules. 4 Responses to kinins are mediated by activation of specific bradykinin receptors. 5,6 In cultured endothelial cells, bradykinin activates protein kinase C through the formation of diacylglycerol, a product of phospholipase C hydrolysis of phosphatidylinositol.7-13 Protein kinase C may be a mediator of pulmonary edema, since the activation of this enzyme with phorbol myristate acetate14-18 or H2O219 produces increases in vascular permeability and/or capillary pressure in isolated lungs and whole animals.…”

Effect of PAF on rat lung vascular permeability: role of platelets and polymorphonuclear leucocytes

“…Results of intravital and light microscopy showed that the action of PAF on vascular permeability is mediated by an early alteration of vascular integrity of the postcapillary venules by formation of gaps between endothelial cells (Bjork & Smedegard, 1983;Humphrey et al, 1984). These changes of endothelial cell integrity have also been demonstrated to occur in response to other inflammatory mediators such as histamine (Majno & Palade, 1961), bradykinin (Svensjo et al, 1979) and peptidoleukotrienes (Dahlen et al, 1981). Heffner et al (1983) showed that the perfusion of PAF together with platelets in isolated perfused lung in vitro caused an acute pulmonary hypertension and oedema which was attributed to TxA2 released from platelets.…”