The bradykinin-induced coronary vasodilation. evidence for an additional prostacyclin-independent mechanism

Schrör, Karsten; Metz, U.; Krebs, R.

doi:10.1007/bf00505936

Cited by 20 publications

(5 citation statements)

References 46 publications

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“…Figure 2 depicts results from a bioassay experiment on an isolated perfused rabbit heart. Stimulation of the heart by bradykinin is followed by a significant release of both PGI2-and PGE2-1ike activities into the coronary effluent (64). Thus, the composition of the prostaglandin fraction appears to be dependent on the type of vessel studied.…”

Section: Prostaglandins and Thromboxanesmentioning

confidence: 97%

Prostaglandins, other eicosanoids and endothelial cells

Schrör

1985

Basic Res Cardiol

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Endothelial cells are an important source of eicosanoid formation in the cardiovascular systems. All major pathways of eicosanoid production have been demonstrated in endothelial cells, yielding significant amounts of prostacyclin (PGI2), PGE2, PGF2 alpha, thromboxane A2, leukotrienes and a number of hydroxy fatty acids. The regulation of eicosanoid formation by endothelial cells is poorly understood. There is evidence that precursors, such as arachidonic acid or prostaglandin endoperoxides, may also be provided by other cell types. Endothelial cell-derived eicosanoids are involved in the regulation of local vessel tone, intravascular platelet activation, cell locomotion and, eventually, cell proliferation. Most of the available information considers PGI2. This compound is the quantitatively dominating eicosanoid in endothelial cells. Major actions of PGI2 include inhibition of platelet activation and aggregation, relaxation of arterial vessels and inhibition of growth-factor release. There is probably a tight interaction with other biologically active mediators which needs further evaluation. This also applies to the clinical significance of eicosanoid-related pathways for the mechanism of action of cardiovascular drugs, such as organic nitrates or acetylsalicylic acid. The unique property of the eicosanoid system to become activated only in response to stimulation, the local nature of this reaction, the multiplicity of products formed and the short half-time of most of them are currently the most significant obstacles to define the role of endothelial cell-derived eicosanoids in clinical practice.

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Section: Prostaglandins and Thromboxanesmentioning

confidence: 97%

Prostaglandins, other eicosanoids and endothelial cells

Schrör

1985

Basic Res Cardiol

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“…We find these results are not unique to the colon. For example, the relaxant activity of kinin on coronary vessels persists after indomethacin has been used to block prostacyclin release (Schror et al, 1979). Also PGE release in the perfused rabbit ear following kinin infusion was not inhibited by calcium-free conditions (Juan, 1979).…”

Section: Possible Involvement Ofcyclic Amp In the Responses To Kininsmentioning

confidence: 99%

Mediators of the secretory response to kinins

Cuthbert

Halushka

Margolius

et al. 1984

British J Pharmacology

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1 The output of immunoreactive (i) 6 keto prostaglandin Fl, (i6ketoPGF1,). iPGE2 and ithromboxane B2 (iTXB2) from isolated colonic epithelium of the rat into the apical and basolateral bathing solution has been measured. In some instances tissues were also voltage clamped at 0 mV to measure short circuit current (SCC). 2 Kallidin (lysylbradykinin) stimulated the output of all three eicosanoids, specifically from the basolateral face of the tissue. The output was similar whether or not the tissues were short circuited. 3 Both the SCC response and eicosanoid output were dependent upon the concentration of kallidin, but not in a strictly proportional manner, there being relatively more eicosanoid output at submaximal kinin concentrations. 4 Indomethacin, 5 JiM, abolished the eicosanoid output, in response to kinin, while some part of the SCC response remained. 5 Calcium removal from the basolateral bathing fluid severely attenuated the SCC response, reduced the output of i6ketoPGFp, to half, but left the output of iPGE2 unchanged. In the presence or absence of calcium it is probable that sufficient PGE material is released to cause part of the SCC changes seen with kinin. 6 Kinin and PGE1 increased the cyclic AMP content of intact epithelia, provided a phosphodiesterase inhibitor was added at the same time.7 It is proposed that kinin causes an increase in calcium influx at the basolateral pole of the tissue. This calcium is necessary for the production of some eicosanoids and the subsequent generation of cyclic AMP, which then increases apical chloride permeability. In addition, calcium may facilitate entry of chloride through the basolateral face of the cells by activating a cotransport mechanism.

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“…ACE inhibitors not only inhibit the con version of angiotensin I to angiotensin II, but additionally inhibit the metabolism of bradykinin [25,26], Bradykinin is released from the ischemic myocardium [27], and is reported to stimulate endogenous prostacy clin formation [28]. A number of studies have reported that prostacyclin or prostacy clin mimetics protect the ischemic and re perfused myocardium [2,29,30], Although increased circulating levels of bradykinin have been difficult to document because of rapid degradation and assay limitations, the observation that inhibitors of prostaglandin formation reverse the antihypertensive ef fects of ACE inhibitors [31,32] supports the contention that prostaglandin formation is stimulated following inhibition of ACE.…”

Section: Discussionmentioning

confidence: 99%

Effects of Two Nonsulfhydryl Angiotensin-Converting Enzyme Inhibitors, CGS 14831 and CGS 16617, on Myocardial Damage and Left-Ventricular Hypertrophy following Coronary Artery Occlusion in the Rat

Smith¹,

Egan²,

Goodman³

et al. 1988

Pharmacology

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The present study was designed to examine the effects of two new angiotensin-converting enzyme (ACE) inhibitors, CGS 14831 and CGS 16617 (3 mg/kg i.v. 1 min prior to occlusion and 4 and 24 h after occlusion), on myocardial ischemic (MI) damage and left-ventricular hypertrophy in rats. Administration of CGS 14831 or CGS 16617 inhibited angiotensin-1-induced pressor responses by 40–100% for 4 h after each dose. Myocardial creatine phosphokinase (CK) levels were 10.6 ± 0.6 U/mg protein in sham-MI animals, and following coronary artery occlusion for 48 h were decreased to 4.1 ± 0.2 U/mg protein in MI + vehicle animals (p < 0.01). CGS 14831 and CGS 16617 attenuated the decrease in CK content and resulted in 47 and 40% sparing, respectively, of the left-ventricular free wall. Neither agent attenuated the left-ventricular hypertrophy which developed following coronary artery occlusion. These data indicate that the nonsulfhydryl ACE inhibitors CGS 14831 and CGS 16617 have a significant cardioprotective effect in rats surviving 48 h, and suggest a potential therapeutic usefulness of these agents for the treatment of ischemia-induced heart failure.

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The bradykinin-induced coronary vasodilation. evidence for an additional prostacyclin-independent mechanism

Cited by 20 publications

References 46 publications

Prostaglandins, other eicosanoids and endothelial cells

Prostaglandins, other eicosanoids and endothelial cells

Mediators of the secretory response to kinins

Effects of Two Nonsulfhydryl Angiotensin-Converting Enzyme Inhibitors, CGS 14831 and CGS 16617, on Myocardial Damage and Left-Ventricular Hypertrophy following Coronary Artery Occlusion in the Rat

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