Endothelium-associated vasodilators in rat skeletal muscle microcirculation

Kaley, Gabor; Rodenburg, J. M.; Messina, Edward J.; Wolin, Michael S.

doi:10.1152/ajpheart.1989.256.3.h720

Cited by 30 publications

(24 citation statements)

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“…6 However, in our current study with aortic rings, the 3-week hypercholesterolemic and control aortic rings constricted to the same degree in response to 10" 6 M norepinephrine. The EDRF-dependent relaxation stimulated by acetylcholine 14 is reduced in both the microcirculation and the aorta (Figure 3) after 3 weeks of the high-cholesterol diet. However, smooth muscle relaxation induced by sodium nitroprusside is not affected by hypercholesterolemia in either the microcirculation or the aorta ( Figure 5).…”

Section: Figure 3 Line Plot Showing Effect Of Increasing Concentratimentioning

confidence: 99%

“…6 The present data, when combined with our previous microvascular study showing decreased responses to norepinephrine, histamine, and mast cell degranulation in 3-week-hypercholesterolemic rats, 6 suggest that receptor-mediated microvascular responses are attenuated by hypercholesterolemia. This attenuation of responses in the microcirculation by hypercholesterolemia includes receptor responses to acetylcholine ( Figure 4, upper panel), which are EDRF mediated, 14 and receptor responses to serotonin (Figures 1 and 2). Preliminary results in the rat cremaster muscle microcirculation suggest that serotonin-induced dilation does not involve EDRF mediation.…”

Section: Figure 3 Line Plot Showing Effect Of Increasing Concentratimentioning

confidence: 99%

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Comparison of early microcirculatory and aortic changes in hypercholesterolemic rats.

Schuschke

Joshua

Miller

1991

Arterioscler Thromb

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The microcirculatory changes caused by hypercholesterolemia were studied in the rat cremaster muscle model by intravital microscopy and were compared with aortic ring segments from the same animals. Male Sprague-Dawley rats were fed either a normal chow diet or a chow diet supplemented with 1% cholesterol and 0.5% cholic acid for 3 or 5 weeks before experimentation. Three weeks of hypercholesterolemia produced a significantly decreased vasodilator response to serotonin in the arterioles. This response was also seen after 5 weeks on the hypercholesterolemia diet Three weeks of hypercholesterolemia produced a significantly increased macromolecular leakage from postcapillary venules in response to serotonin. However, after 5 weeks of hypercholesterolemia, the serotonin-induced leakage was less than in control animals. Hypercholesterolemia for 3 weeks decreased the arteriolar dilation evoked by acetylcholine but did not change the arteriolar response to sodium nitroprusside. Contraction of the aortic rings induced by serotonin and aortic ring relaxation induced by sodium nitroprusside were not different between 3-week-control and 3-week-hypercholesterolemic animals. However, 3 weeks of hypercholesterolemia attenuated the aortic ring relaxation evoked by acetylcholine. These results suggest that hypercholesterolemia causes an early depression of endothelium-derived relaxing factor (EDRF)-mediated receptor responses in both microvessels and the aorta, whereas non-EDRF-mediated receptor responses are altered in the microcirculation but not in the aorta. (Arteriosclerosis and Thrombosis 1991;ll:154-160) I n several animal models, hypercholesterolemia has been shown to cause abnormal aortic and coronary artery reactivity preceding the onset of atherosclerotic lesions. Diet-induced hypercholesterolemia significantly increased maximal aortic responses to norepinephrine, histamine, and serotonin after 4 weeks of high-cholesterol feeding in rabbits. 1 However, after 8 weeks on the hypercholesterolemia diet, these responses became attenuated as lipid deposition occurred in the artery walls. The response to norepinephrine in canine coronary arteries was potentiated by 4-5 weeks of a high-cholesterol diet. 2 In contracted porcine coronary arteries, endothelium-dependent relaxations caused by serotonin were reduced by hypercholesterolemia, 34 while endothelium-independent relaxations caused by sodium nitroprusside were unaffected. 3 Endothelium-derived relaxing factor (EDRF) relaxation evoked by acetylcholine was also decreased in the aortas of

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Section: Figure 3 Line Plot Showing Effect Of Increasing Concentratimentioning

confidence: 99%

Section: Figure 3 Line Plot Showing Effect Of Increasing Concentratimentioning

confidence: 99%

Comparison of early microcirculatory and aortic changes in hypercholesterolemic rats.

Schuschke

Joshua

Miller

1991

Arterioscler Thromb

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“…PGE 2 and PGF 2␣ were prepared in Krebs-Henseleit buffer according to the supplier's recommendations. The concentrations and mode of administration of PGE 2 and PGF 2␣ in these experiments were based on the experience of other investigators utilizing similar experimental models (4,5,15,23,30,34). The addition of these substances to the Krebs-Henseleit buffer had no effect on the pH of the perfusate.…”

Section: Experimental Protocolmentioning

confidence: 99%

Prostaglandins potentiate U-46619-induced pulmonary microvascular dysfunction

Wright¹,

Kim²,

Rogers

et al. 2000

Journal of Applied Physiology

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.-The induction of cyclooxygenase is an important event in the pathophysiology of acute lung injury. The purpose of this study was to examine the synergistic effects of various cyclooxygenase products (PGE 2 , PGI 2 , PGF 2␣ ) on thromboxane A 2 (TxA 2 )-mediated pulmonary microvascular dysfunction. The lungs of SpragueDawley rats were perfused ex vivo with Krebs-Henseleit buffer containing indomethacin and PGE 2 (5 ϫ 10 Ϫ8 to 1 ϫ 10 Ϫ7 M), PGF 2␣ (7 ϫ 10 Ϫ9 to 5 ϫ 10 Ϫ6 M), or PGI 2 (5 ϫ 10 Ϫ8 to 2 ϫ 10 Ϫ5 M). The TxA 2 -receptor agonist U-46619 (7 ϫ 10 Ϫ8 M) was then added to the perfusate, and then the capillary filtration coefficient (K f ), pulmonary arterial pressure (Ppa), and total pulmonary vascular resistance (RT) were determined. The K f of lungs perfused with U-46619 was twice that of lungs perfused with buffer alone (P ϭ 0.05). The presence of PGE 2 , PGF 2␣ , and PGI 2 within the perfusate of lungs exposed to U-46619 caused 118, 65, and 68% increases in K f , respectively, over that of lungs perfused with U-46619 alone (P Ͻ 0.03). The RT of lungs perfused with PGE 2 ϩ U-46619 was ϳ30% greater than that of lungs exposed to either U-46619 (P Ͻ 0.02) or PGE 2 (P Ͻ 0.01) alone. When paired measurements of RT taken before and then 15 min after the addition of U-46619 were compared, PGI 2 was found to attenuate U-46619-induced increases in RT (P Ͻ 0.01). These data suggest that PGE 2 , PGI 2 , and PGF 2␣ potentiate the effects of TxA 2 -receptor activation on pulmonary microvascular permeability.capillary filtration coefficient; pulmonary vascular resistance; isolated perfused lung model THROMBOXANE A 2 (TxA 2 ) has been incriminated as an important mediator of the pulmonary microvascular dysfunction that characterizes tissue ischemia and reperfusion injury (29), endotoxin exposure (9), and cutaneous thermal injury (14). In these conditions, as well as others, TxA 2 has been shown to cause vasoconstriction and enhanced microvascular permeability. Upregulation of cyclooxygenase is an important event in the generation of TxA 2 during acute inflammatory states. Cyclooxygenase catalyzes the incorporation of molecular oxygen into arachidonic acid, yielding a cyclic endoperoxide (PGG 2 ); subsequent peroxidation yields PGH 2 , the precursor for the synthesis of TxA 2 and PGE 2 , PGI 2 , and PGF 2␣ . In general, each of these cyclooxygenase products is released by the lung in response to a particular inflammatory stimulus, albeit in varying amounts (9,14).Despite their common origin, the physiological effects of these substances on the pulmonary microvasculature are diverse. For example, TxA 2 and PGF 2␣ are constrictors of the pulmonary vasculature in rats, whereas PGI 2 is a potent vasodilator (4, 5). Furthermore, TxA 2 profoundly increases microvascular permeability, whereas the other agents have little, if any, effect by themselves (20, 27). Several investigators have reported that PGE 2 and PGI 2 potentiate the effects of histamine, bradykinin, and interleukin-1 on microvascular permeability (2,34,35). Thi...

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“…This was subsequently found to be true for many other vasoactive substances.2-6 As a result of work from several laboratories, this response has been shown to occur because the endothelium releases a shortlived nonprostanoid compound or family of compounds collectively termed the "endotheliumSee p 458 and p 466 derived relaxing factor" (EDRF).7,8 These substances relax vascular smooth muscle by activating guanylate cyclase9,10 and by producing transient smooth muscle hyperpolarization.11 The role of EDRF in regulating vascular tone was first implicated in large vessels but has now been extended to the microcirculation. 12 …”

mentioning

confidence: 99%

From isolated vessels to the catheterization laboratory. Studies of endothelial function in the coronary circulation of humans.

Harrison

1989

Circulation

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Endothelium-associated vasodilators in rat skeletal muscle microcirculation

Cited by 30 publications

References 0 publications

Comparison of early microcirculatory and aortic changes in hypercholesterolemic rats.

Comparison of early microcirculatory and aortic changes in hypercholesterolemic rats.

Prostaglandins potentiate U-46619-induced pulmonary microvascular dysfunction

From isolated vessels to the catheterization laboratory. Studies of endothelial function in the coronary circulation of humans.

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