Mechanism and modification of bradykinin-induced coronary vasodilation.

Abstract

In isolated perfused rabbit hearts, bradykinin produced a concentration-dependent decrease in coronary resistance directly associated with biosynthesis and release of prostaglandin-E-like substance. An inhibitor of bradykinin destruction (the nonapeptide SQ-20881) markedly enhanced both the coronary vasodilation and release of prostaglandin-E-like substance produced by cardiac injection of bradykinin. Indomethacin inhibited both the myocardial prostaglandin biosynthesis and the decrease in coronary resistance induced by bradykinin. The demonstration that bradykinin is a potent stimulator of prostaglandin biosynthesis in the heart has implications as to the cause of the afferent cardiovascular reflexes and pain in myocardial infarction and angina pectoris.Bradykinin is generated by the action of a proteolytic enzyme upon plasma alpha-2-globulin. Since proteolytic enzymes are ubiquitous in the body, all tissues presumably are capable of releasing bradykinin from plasma (1). Bradykinin has repeatedly been demonstrated to be one of the most potent coronary dilators in isolated perfused mammalian hearts (2) as well as in intact animals (3-5). Indeed, there is evidence to suggest that bradykinin is involved in the local humoral control of coronary blood flow. The bradykinin-induced coronary vasodilation could be the result of either a direct relaxation of coronary vascular smooth muscle or an indirect action by means of an endogenous substance. As to the second possibility, the action of bradykinin on coronary resistance does not appear to be the result of the elaboration of histamine, catecholamines, acetylcholine, or serotonin (2, 3).To establish that an endogenous substance mediates a physiologic event requires temporal and quantitative correlation between changes in concentration of the putative mediator with changes in functional status of the organ. The concentration of the mediator substance should be proportional to the stimulus (bradykinin in this case) and, in addition, abolition of the synthesis of the mediator should abolish the physiologic action of the stimulus. In view of the previous demonstration that the heart readily synthesizes and releases prostaglandins (6-8), we have investigated the possible involvement of endogenously synthesized prostaglandins in mediating the coronary vasodilation produced by bradykinin in isolated perfused rabbit hearts. METHODSIsolated rabbit (New Zealand) hearts were perfused through the aorta with Krebs-Henseleit medium (in an atmosphere of 95% 02 and 5% C02) at a constant flow of 30 ml/min. Abbreviation: PG, prostaglandin.Changes in perfusion pressure (Statham transducer, Brush recorder) were indicative of alterations in coronary resistance. Ventricular pressure and rate were recorded from a fluidfilled balloon tied into the left ventricle (isovolumic heart).The coronary venous effluent was continuously and immediately assayed for the presence of vasoactive substances. This was achieved by continuously superfusing a series of isolated assay tissues with the coro...

Regulation of bradykinin receptor level by cholera toxin, pertussis toxin and forskolin in cultured human fibroblasts

“…Many of these effects appear to be mediated by arachidonic acid metabolites. For example, prostacyclin, which is released from the heart in response to bradykinin, mimics bradykinin induced dilatation of coronary vessels (Needleman et al, 1975); and in the kidney, bradykinin causes the release of prostaglandin E2, which stimulates salt and water excretion (McGiff et al, 1976).…”

Effects of arachidonic acid and bradykinin on the coronary flow, release of PGI2 and cardiac functions in the perfused guinea-pig heart.

“…Needleman et al (2) suggested that the BK-induced coronary vasodilation seen in isolated rabbit heart preparations was mediated via the release of prostaglandins. Later, it was argued that PGI2 might play a main role in the coronary action of BK in isolated rabbit hearts (4).…”

“…Arachidonic acid (AA) and bradykinin (BK) have potent coronary vasodilating actions in isolated mammalian hearts (1,2). The vasodilating action of AA is attributed to a metabolic product of AA, prostacyclin (PG12) (3), which has been described as being a prostaglandin-like substance (PLS).…”

The influence of the kallikrein-kinin system on the characteristics of insulin receptors in rat skeletal muscle during ischemia

“…This phenomenon can be observed both in heart and skeletal muscle tissues (Needleman et al, 1975;Dietze et al, 1984). Tissue acidosis stimulates the activity of kallikreins leading to enhanced release of kinins (Regoli et al, 1980;Dietze et al, 1982), which in turn directly or by stimulation of prostaglandin synthesis stabilize a pool of cellular high-energy compounds during both ischemia and reperfusion (Zhu et al, 1995).…”