Acetylcholine and Bradykinin Relax Intrapulmonary Arteries by Acting on Endothelial Cells: Role in Lung Vascular Diseases

Chand, N.; Altura, Burton M.

doi:10.1126/science.7268440

Cited by 219 publications

(71 citation statements)

References 5 publications

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“…Bradykinin is able to elicit an endotheliumdependent relaxation of a large variety of canine arteries (Chand & Altura, 1981;Cherry et al, 1982). Such a bradykinin-induced relaxation was also found to occur in pig aorta (Gordon & Martin, 1983), in bovine intrapulmonary artery and vein (Gruetter & Lemke, 1986a) and in bovine coronary artery (Angus et al, 1986b).…”

Section: Discussionmentioning

confidence: 97%

Modulatory role of the vascular endothelium in the contractility of human isolated internal mammary artery

Schoeffter

Dion

Godfraind

1988

British J Pharmacology

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1 Endothelium-dependent relaxant responses and modulation of contractile responses were investigated in human isolated 'internal mammary artery (HIMA), a vessel widely used for coronary bypass surgery.2 Acetylcholine and ionophore A23187 (both l0nM-l pM) elicited concentration-dependent relaxations of precontracted HIMA. These relaxations were abolished after rubbing of the endothelium, they were inhibited by methylene blue and were insensitive to indomethacin.3 Histamine at concentrations lower than 10pM elicited an endothelium-dependent, methylene blue-sensitive relaxation of precontracted HIMA. This effect of histamine was inhibited by the Hl-receptor antagonist mepyramine. Bradykinin, noradrenaline and a2-adrenoceptor agonists (in the presence of prazosin) did not relax unrubbed HIMA in which acetylcholine or A23187 were shown to be efficient.4 Tissue levels of guanosine-3':5'-monophosphate (cyclic GMP) were found to be significantly higher in unrubbed HIMA rings than in matched rubbed rings. 5 Methylene blue evoked a slow contraction in resting HIMA, and this contraction was significantly greater in unrubbed than in rubbed preparations. Also, methylene blue enhanced the contractile response of HIMA to noradrenaline and this potentiating effect was significantly greater in unrubbed than in rubbed preparations. Indomethacin induced a slow contraction, of similar magnitude in unrubbed and rubbed HIMA rings.6 In resting HIMA, the concentration-effect curve of noradrenaline-induced contraction was significantly shifted to the left after rubbing of the endothelium, without change in the maximal responses. In unrubbed rings the EC50 value of noradrenaline was about 2 fold that in rubbed rings.7 Histamine also contracted resting HIMA in a concentration-dependent manner and in addition, it triggered rhythmic activity. This rhythmic activity was more prominent in unrubbed preparations and could be partially inhibited by indomethacin. The concentration-effect curve of histamineinduced contractions was displaced to the left after rubbing the endothelium, without changes in the maximal responses. The EC50 value of histamine in unrubbed rings was 4 to 9 fold that found in rubbed rings, depending on the level of tension taken into account for the concentration-effect curve during rhythmic contractions. 8 In the presence of nifedipine (3 pM), noradrenaline-induced contractions were not significantly altered, whereas histamine-induced contractions were found to be inhibited by about 70%. 9 It is concluded that in HIMA, both spontaneous and stimulated endothelium-dependent relaxing factor (EDRF) release may occur, and that basal EDRF can itself be responsible for the modulatory effect of endothelium on contractile responses.

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Section: Discussionmentioning

confidence: 97%

Modulatory role of the vascular endothelium in the contractility of human isolated internal mammary artery

Schoeffter

Dion

Godfraind

1988

British J Pharmacology

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“…Although the nature of EDRF has never been clearly explained, the activities of these EDRF inhibitors have led investigators to propose a number of possible sources for EDRF, including oxidative products of the lipoxygenase or epoxygenase pathways of arachidonate metabolism (25-27). Further studies showed that pulmonary artery strips had the capacity to respond to endothelium-dependent vasodilators (7,28). In view of these previous investigations, the results presented here demonstrate endothelium-dependent vasodilation in the pulmonary vascular bed, and are consistent with an important role of the endothelium in the modulation of the hypoxic pressor response of the intact pulmonary vascular bed through the release of EDRF.…”

Section: Discussionmentioning

confidence: 99%

“…As the role of the endothelium was investigated further, it was apparent that endothelium-dependent relaxation was due to release of a diffusible factor(s), as the relaxation was transferable in perfusate to vascular strips denuded of endothelium (6). This factor appeared to be a nonprostaglandin substance since vascular responsiveness to endothelium-dependent vasodilators was unchanged by treatment with cyclooxygenase inhibitors (7,8). However, the actions of these endothelium-dependent relaxing factors (EDRF)' were attenuated or blocked by multiple pharmacological agents, including the lipoxygenase antagonists eicosatetrayenoic acid (ETYA) and nordihydroguaiaretic acid (NDGA) (8) and the antioxidant hydroquinone (HQ) (6).…”

Section: Introductionmentioning

confidence: 99%

Augmentation of hypoxic pulmonary vasoconstriction in the isolated perfused rat lung by in vitro antagonists of endothelium-dependent relaxation.

Brashers¹,

Peach²,

Rose³

1988

J. Clin. Invest.

131

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The role of the endothelium in hypoxic constriction of the intact pulmonary vascular bed has not been clearly elucidated.To test for a possible role for endothelium-derived relaxing factor(s) (EDRF) in the hypoxic pressor response, isolated, whole blood-perfused rat lungs from male Sprague-Dawley rats treated with meclofenamate were prepared. Three protocols were performed, including: (a) normal saline (control); (b) the putative EDRF inhibitors, eicosatetraynoic acid (ETYA, 1 X 10-4 M) or nordihydroguaiaretic acid (NDGA, 1 X 10-4 M) versus vehicle DMSO; and (c) the putative EDRF inhibitor hydroquinone (HQ, 1 X 10-4 M) versus vehicle ethyl alcohol (ETOH). The pulmonary pressor response to angiotensin II (Ang II, 0.25 Mg) injections alternated with 6-min periods of hypoxic ventilation (3% 02,5% C02) was measured before and after the administration of saline, inhibitors, or vehicles. The administration of the EDRF inhibitors ETYA, NDGA, and HQ resulted in a marked accentuation of the hypoxic pressor response that was not seen in the controls (P < 0.05). In separate experiments, lungs precontracted with norepinephrine (1 X 10-6 M) were pretreated with edrophonium (1 X 10-4 M) and then observed for endothelium-dependent vasodilator responses to acetylcholine at increasing doses (1 X 10-7 X 10-4 M). Administration of ETYA, NDGA, or HQ abrogated the observed vasodilatation to acetylcholine, which was not seen with vehicles alone (P < 0.01). These studies suggest an important role for the endothelium in pulmonary vascular responsiveness to alveolar hypoxia through possible release of a relaxing factor(s) that attenuates the degree of pulmonary arterial constriction.

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“…Furthermore, in microvessel beds of the cheek pouch and cremaster muscle of the hamster, arteriolar dilatation is produced by suffusing the tissues with hyperosmotic solutions. The dilatation requires between 2 and 5 min to reach full effect (Duling & Staples, 1976 Acetylcholine, bradykinin and histamine, however, evoke relaxation of large arteries in vitro by similar mechanisms which involve the release of a substance by the endothelial cell (Furchgott & Zawadzki, 1980;Chand & Altura, 1981a; Van de Voorde & Leusen, 1982). It was relevant, therefore, to test the response of large arteries from normal and diabetic animals to these agents.…”

Section: Discussionmentioning

confidence: 99%

Vascular reactivity in diabetes mellitus: role of the endothelial cell

Fortes

Lerne

Scivoletto

1983

British J Pharmacology

130

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1 The response to vasoactive agents of microvessels in situ and large arteries in vitro was compared in normal and alloxan-diabetic rats. 2 Noradrenaline was equally effective in evoking a constrictor response of mesenteric microvessels in normal and diabetic animals. 3 The constrictor response to a standard amount of noradrenaline in such vessels was fully antagonized by acetylcholine or papaverine, the minimum effective doses being equivalent in normal and diabetic animals. In contrast, the minimum doses of histamine or bradykinin, effective in normal animals, had to be increased about 20 fold to be active in diabetic animals. 4 Increased osmolarity of extracellular fluid caused a significant and equivalent increase in latency of the vasoconstrictor response of microvessels to noradrenaline in normal and diabetic animals. 5 Concentration-effect curves, constructed from the response of isolated aortae to noradrenaline, were similar in normal and diabetic animals, provided the endothelium was removed. Diabetes only affected preparations in which the endothelium was left intact. In these, the median effective concentrations of noradrenaline were greatly increased in comparison with normal values. 6 Precontracted aortae from normal and diabetic animals were equally relaxed by acetylcholine and histamine, provided the endothelium was left intact. Loss of the relaxant response of the preparations in all groups of animals was observed following removal of endothelial cells. 7 It is suggested that different mechanisms may be involved in the effects of vasodilator agents on large arteries in vitro or small vessels in situ. Histamine and bradykinin which are potent permeability-increasing factors, may antagonize the vasoconstrictor response of microvessels to noradrenaline through an action on endothelial cells with increased vascular permeability and temporary changes in composition of extracellular fluid. The reactive process of endothelial cells to permeability factors was affected by diabetes mellitus. However, the response of microvessels to acetylcholine and papaverine which are devoid of permeability-increasing properties, was not influenced by diabetes.

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Acetylcholine and Bradykinin Relax Intrapulmonary Arteries by Acting on Endothelial Cells: Role in Lung Vascular Diseases

Cited by 219 publications

References 5 publications

Modulatory role of the vascular endothelium in the contractility of human isolated internal mammary artery

Modulatory role of the vascular endothelium in the contractility of human isolated internal mammary artery

Augmentation of hypoxic pulmonary vasoconstriction in the isolated perfused rat lung by in vitro antagonists of endothelium-dependent relaxation.

Vascular reactivity in diabetes mellitus: role of the endothelial cell

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