Coronary vasoconstriction and PGI2 release by leukotrienes in isolated guinea pig hearts

Terashita, Zen‐ichi; Fukui, Hiroshi; Hirata, Minoru; Terao, Shinji; Ohkawa, Shigenori; Nishikawa, Kokei; Kikuchi, Shintarō

doi:10.1016/0014-2999(81)90238-7

Cited by 88 publications

(30 citation statements)

References 9 publications

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“…The maintenance of cardiac output during the initial pressor phase in our model could be explained by increased myocardial contractility or increased left ventricular filling or both. A few studies have indicated a positive inotropic action of LTD 4 on guinea pig atria 26 ; others have reported cardiodepression 12 -"• 16 or no effect of LTD 4 on contractility after systemic administration of a high dose of LTD 4 to Sprague-Dawley rats. 13 We found that dp/dt was increased by 60% shortly after LTD 4 administration to SHR, which suggests an increase in contractility especially as the heart faced a simultaneous increase in afterload in this period.…”

Section: Discussionmentioning

confidence: 99%

Overall and regional hemodynamic effects of leukotriene D4 in spontaneously hypertensive rats.

Zukowska‐Grojec¹,

Bayorh²,

Kopin³

et al. 1985

Hypertension

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SUMMARY Leukotriene D 4 , a constituent of slow-reacting substance of anaphylaxis, elicits a pressor response followed by nypotensive shock in spontaneously hypertensive rats but not in other rats. Hemodynamic mechanisms underlying this pattern in spontaneously hypertensive rats, pithed and vagotomized to eliminate circulatory reflexes, were studied using radiolabeleti microspheres. One minute after leukotriene D 4 administration (20 fig/kg i.v.), mean arterial pressure increased by 54 mm Hg, total peripheral resistance index increased by 68%, heart rate decreased by 34 beats/minute, and cardiac index was unchanged. Profound reductions of blood flow and increases of vascular resistance in the hepatosplanchnic area, skeletal muscles, and skin also occurred. Five minutes later, mean arterial pressure remained elevated ( + 35%), hematocrit rose (+17%), and total peripheral resistance index increased, which offset 40% decreases in cardiac and stroke volume indices. Ten minutes after leukotriene D 4 administration, during hypotension, cardiac and stroke volume indices and blood flow to all vascular beds declined further while total peripheral resistance index and hematocrit (+ 28%) continued to rise. In Wistar-Kyoto rats, administration of leukotriene D 4 caused less of a pressor response ( + 34 mm Hg) because vascular resistance was increased only in skeletal muscles, which was followed by a slight hypotension without any significant changes in cardiac and stroke volume indices, total or regional vascular resistance, and hematocrit. Thus, in spontaneously hypertensive rats the leukotriene D 4 -induced pressor response appears to be caused by generalized vasoconstriction, and the subsequent hypotension appears to result not from vascular collapse but from reduced cardiac output. (Hypertension 7: 507-513, 1985) KEY WORDS • leukotrienes • blood pressure • cardiac output • total peripheral resistance • regional blood flow • regional vascular resistance • spontaneously hypertensive rats • Wistar-Kyoto rats A CUTE anaphylaxis is characterized by severe / \ hemodynamic changes, cardiac arrhythmias, A. \ -and myocardial ischemia. All these phenomena can be elicited by systemic or intracardiac administration of slow-reacting substance of anaphylaxis. 1 " 3 Recently, leukotriene D 4 (LTD 4 ) and C 4 (LTC 4 ), 5-lipoxygenase metabolites of arachidonic acid, were identified as major constituents of slow-reacting substance of anaphylaxis^ and were shown to cause bronchoconstriction, 4. 7. 8 vasoconstnction, 4. 7-14 cardiodepression, 9 l2~16 and increased venular permeabil- j t y 4.6. i7. i8 Aft er systemic administration of leukotrienes to some animal species, an initial arteriolar constriction and rise in blood pressure are followed by a transient hypotensive period. This biphasic response to LTD,, and LTC 4 is characteristic of guinea pig, monkey, and sheep 7 ' l2 -l4 but is uncommon in various species of rats."-' 3 -l9~21 Spontaneously hypertensive rats (SHR), however, are extremely sensitive to the cardiovascular effects ...

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Section: Discussionmentioning

confidence: 99%

Overall and regional hemodynamic effects of leukotriene D4 in spontaneously hypertensive rats.

Zukowska‐Grojec¹,

Bayorh²,

Kopin³

et al. 1985

Hypertension

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“…On the other hand, the lack of effect of NDGA on TXB2 release suggests that endogenous SRS-A does not liberate TXB2 from isolated anaphylactic guinea-pig hearts. This assumption is supported by results (Terashita et al, 1981) showing that exogenous leukotrienes do not release TXB2 from guinea-pig isolated perfused hearts. In the guinea-pig lung, however, exogenous LTC4 (Folco, Hansson & Granstrom, 1981) as well as SRS-A (Engineer, Morris, Piper & Sirois, 1978) have been demonstrated to release TXA2, indicating an organ specificity as to the cyclo-oxygenase products released by leukotrienes.…”

Section: Discussionmentioning

confidence: 53%

“…Alternatively, the decreased release of 6-keto-PGF1, into the heart perfusates may be a consequence of the inhibition of SRS-A release by NDGA. In fact, release of 6-keto-PGFi, by exogenous leukotrienes from isolated perfused guinea pig hearts has been demonstrated (Terashita et al, 1981). On the other hand, the lack of effect of NDGA on TXB2 release suggests that endogenous SRS-A does not liberate TXB2 from isolated anaphylactic guinea-pig hearts.…”

Section: Discussionmentioning

confidence: 99%

“…Exogenous LTC4 and LTD4 are, in fact, potent coronary constrictors (Terashita, Fukui, Hirata, Terao, Ohkawa, Nishikawa & Kikuchi, 1981;Letts & Piper, 1982; Burke, Levi, Guo & Corey, 1982). In order to investigate further the contribution of endogenous SRS-A to anaphylactic coronary flow reduction we have now used the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) (Tappel, Lundberg & Boyer, 1953;Hamberg, 1976) and the SRS-A antagonist, FPL 55712 (Augstein, Farmer, Lee, Sheard & Tattersall, 1973).…”

Section: Introductionmentioning

confidence: 99%

“…The use of a radioimmunoassay for LTC4, developed recently (Aehringhaus, W61bling, Konig, Patrono, Peskar & Peskar, 1982), permitted quantification of LTC4-like immunoreactivity in the presence of the antagonist FPL55712, when bioassay of SRS-A is not possible. Finally, since exogenous leukotrienes release 6-keto-PGF1,, but not TXB2 (Terashita et al, 1981), from guinea-pig isolated perfused hearts, we have additionally examined the effects of NDGA and FPL 55712 on the release of these cyclo-oxygenase products during cardiac anaphylaxis. Some of these results have been reported at the Annual Symposium on Leukotrienes and Other Lipoxygenase Products, London, 1982 (Wittenberg, W6lbling, Aehringhaus, Patrono, Peskar & Peskar, 1983).…”

Section: Introductionmentioning

confidence: 99%

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Effect of inhibition of synthesis and receptor antagonism of SRS‐ A in cardiac anaphylaxis

Aehringhaus

Peskar

Wittenberg

et al. 1983

British J Pharmacology

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1 The effects of infusions of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 1.1 x 10-molmin-') and the antagonist of slow-reacting substance of anaphylaxis (SRS-A) FPL 55712 (1.2 x 10-mol min-') on the coronary constriction and the release of SRS-A, leukotriene C4-like immunoreactivity, thromboxane B2 and 6-keto-prostaglandin Fl. from perfused anaphylactic guinea-pig hearts were investigated. 2 Both NDGA and FPL 55712 in the concentrations used induced an increase in basal coronary flow, but did not prevent the coronary flow reduction in the early phase (0-4 min) after antigen injection. On the other hand, NDGA and FPL 55712 inhibited the less pronounced long-lasting coronary flow reduction in the later phase of cardiac anaphylaxis. 3 NDGA decreased the release of SRS-A from the anaphylactic guinea-pig hearts below or close to the detection limit of the bioassay and simultaneously diminished the release of leukotriene C4-like immunoreactivity. On the other hand, FPL 55712 did not influence the amounts of leukotriene C4-like immunoreactivity released in cardiac anaphylaxis. 4 Neither NDGA nor FPL 55712 affected the release of immunoreactive thromboxane B2 (TXB2) from anaphylactic guinea-pig hearts. Release of 6-keto-prostaglandin Flm after challenge, however, was decreased by NDGA, while FPL 55712 had no significant effect. 5 These results suggest, that SRS-A may be a relatively more important mediator in the late phase of coronary constriction occurring during cardiac anaphylaxis, while the effects of other mediators, particularly vasoconstrictor cyclo-oxygenase products, seem to prevail in the early phase.

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Leukotrienes in COPD: The Unexploited Potential

Dahlén

Stockley

Rennard

et al. 2007

Chronic Obstructive Pulmonary Disease

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Coronary vasoconstriction and PGI2 release by leukotrienes in isolated guinea pig hearts

Cited by 88 publications

References 9 publications

Overall and regional hemodynamic effects of leukotriene D4 in spontaneously hypertensive rats.

Overall and regional hemodynamic effects of leukotriene D4 in spontaneously hypertensive rats.

Effect of inhibition of synthesis and receptor antagonism of SRS‐ A in cardiac anaphylaxis

Leukotrienes in COPD: The Unexploited Potential

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