The Epinephrine Response of Isolated Rabbit Vascular Strips After in Vivo and in Vitro Endotoxin Exposure

Wright, Robert C.; Winkelmann, R. K.

doi:10.1177/000331977102200901

Cited by 2 publications

(2 citation statements)

References 13 publications

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“…The depression ofcarotid contractility by LPS-activated macrophages or their supernatants was not due to direct action by LPS, because LPS alone had no significant effect throughout the time course of our experiments, in agreement with previous results (12 On to macrophage functional phenotypes. In the present work, quiescent resident macrophages were fully activated by LPS via a state of elicitation induced by intraperitoneal injection of sterile mineral oil.…”

Section: Discussionsupporting

confidence: 93%

Activated macrophages depress the contractility of rabbit carotids via an L-arginine/nitric oxide-dependent effector mechanism. Connection with amplified cytokine release.

Bernard

Szekély²,

Philip³

et al. 1992

J. Clin. Invest.

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Inflammatory mediators released by macrophages (M+) are believed to be involved in septic vasoplegia. To investigate the effect of My on vascular reactivity, excised rabbit carotids were exposed intraluminally either to peritoneal rabbit ME, activated by 18 h of incubation with 1 gg/ml lipopolysaccharide, or to the supernatants (SPN) derived from them. The contractile responses to phenylephrine (PE, 10-6 M) were determined by measuring changes in diameter using an ultrasonic microdimensiometer 1, 2, and 3 h after the first control contraction. In control arteries (n = 12), PE-induced contractions were, respectively, 102.9±3.3%, 95.2±4.1%, and 89.7±3.8% of the first contraction, after 1, 2, and 3 h. Activated M4 significantly reduced PE-stimulated contractions after as little as 1 h of carotid exposure (percentage of controls at 1, 2, or 3 h: 74.1±5.6, 57.2±5.2, and 34.2±5.6, n = 10, P < 0.001). The activated macrophage-derived SPN took longer to diminish carotid contractility than the Mt themselves, and became significant only after 2 h. The greater effect of Mt might be due to cooperation between Mt and vascular cells, as suggested by the amplified interleukin-1 release observed after Mt infusion. The presence of the endothelium partially protected carotid contractility from depression by activated Mt. Extraluminal addition of NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis prevented this depression in arteries with or without endothelium. No products of the oxidative pathway of L-arginine were detected in rabbit activated Mt. These results suggest that activation of this pathway in smooth muscle cells seems to be involved in vascular hypocontractility. (J. Clin.

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Section: Discussionsupporting

confidence: 93%

Activated macrophages depress the contractility of rabbit carotids via an L-arginine/nitric oxide-dependent effector mechanism. Connection with amplified cytokine release.

Bernard

Szekély²,

Philip³

et al. 1992

J. Clin. Invest.

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“…Vascular hyporeactivity to vasoconstrictors is character-ized by the reduced sensitivity of the vasculature to vasopressor agents. A large body of evidence supports the pathophysiological generation of excess NO in septic shock through the expression of inducible NO synthase (iNOS) in the vasculature and myocardium, which contributes to vasodilatation, vascular hyporeactivity, and cardiac collapse (2,10,15,16,32,35,38,45,49).…”

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confidence: 99%

Inhibition of matrix metalloproteinase activity in vivo protects against vascular hyporeactivity in endotoxemia

Cena¹,

Lalu²,

Cho³

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Persistent arterial hypotension is a hallmark of sepsis and is believed to be caused, at least in part, by excess nitric oxide (NO). NO can combine with superoxide to produce peroxynitrite, which activates matrix metalloproteinases (MMPs). Whether MMP inhibition in vivo protects against vascular hyporeactivity induced by endotoxemia is unknown. Male Sprague-Dawley rats were administered either bacterial lipopolysaccharide (LPS, 4 mg/kg ip) or vehicle (pyrogen-free water). Later (30 min), animals received the MMP inhibitor doxycycline (4 mg/kg ip) or vehicle (pyrogen-free water). After LPS injection (6 h), animals were killed, and aortas were excised. Aortic rings were mounted in organ baths, and contractile responses to phenylephrine or KCl were measured. Aortas and plasma were examined for MMP activity by gelatin zymography. Aortic MMP and inducible nitric oxide synthase (iNOS) were examined by immunoblot and/or immunohistochemistry. Doxycycline prevented the LPS-induced development of ex vivo vascular hyporeactivity to phenylephrine and KCl. iNOS protein was significantly upregulated in aortic homogenates from endotoxemic rats; doxycycline did not alter its level. MMP-9 activity was undetectable in aortic homogenates from LPS-treated rats but significantly upregulated in the plasma; this was attenuated by doxycycline. Plasma MMP-2 activities were unchanged by LPS. Specific MMP-2 activity was increased in aortas from LPS-treated rats. This study demonstrates the in vivo protective effect of the MMP inhibitor doxycycline against the development of vascular hyporeactivity in endotoxemic rats.

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The Epinephrine Response of Isolated Rabbit Vascular Strips After in Vivo and in Vitro Endotoxin Exposure

Cited by 2 publications

References 13 publications

Activated macrophages depress the contractility of rabbit carotids via an L-arginine/nitric oxide-dependent effector mechanism. Connection with amplified cytokine release.

Activated macrophages depress the contractility of rabbit carotids via an L-arginine/nitric oxide-dependent effector mechanism. Connection with amplified cytokine release.

Inhibition of matrix metalloproteinase activity in vivo protects against vascular hyporeactivity in endotoxemia

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