Cigarette smoke extract contracts isolated porcine coronary arteries by superoxide anion-mediated degradation of EDRF

To test whether cigarette smoke extract (CSE) influences the endothelial regulation of vascular tone in vitro, pig coronary arterial rings were incubated in organ chambers and isometric tension changes were examined. CSE was prepared by bubbling mainstream smoke of one filter cigarette into phosphate-buffered saline (2 ml). Fresh CSE (3.3, 10, and 30 microliters/ml) elicited initial contraction and subsequent relaxation during stable contraction to prostaglandin F2 alpha (PGF2 alpha). Initial contraction to CSE was dependent on the presence of endothelium, whereas subsequent relaxation was endothelium independent. Initial contraction was significantly attenuated by superoxide dismutase (SOD), methylene blue, but not by catalase. Prior inhibition of the basal release of endothelium-derived relaxing factor by NG-monomethyl-L-arginine also inhibited the initial contraction, and this inhibition was reversed by coincubation with L-arginine but not D-arginine. Subsequent relaxation was significantly potentiated by SOD but was markedly attenuated by methylene blue. CSE reduced ferricytochrome c, and this reduction was significantly inhibited by SOD. In conclusion, CSE induced biphasic tension change, initial contraction, and subsequent relaxation during stable contraction to PGF2 alpha in isolated pig coronary arteries. The initial contraction may be, at least in part, mediated through the degradation of basally released endothelium-derived relaxing factor (nitric oxide) by superoxide anions derived from CSE.

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Canine arteries release two different endothelium-derived relaxing factors

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.257.1.h330 ◽

1989 ◽

Vol 257 (1) ◽

pp. H330-H333 ◽

Cited By ~ 6

Author(s):

U. Hoeffner ◽

M. Feletou ◽

N. A. Flavahan ◽

P. M. Vanhoutte

Keyword(s):

Endothelial Cells ◽

Smooth Muscle ◽

Coronary Artery ◽

Vascular Smooth Muscle ◽

Coronary Arteries ◽

Relaxing Factor ◽

Prostaglandin F2 Alpha ◽

Donor Artery ◽

Canine Coronary Artery ◽

Endothelium Derived Relaxing Factor

Experiments were designed to analyze the effects of ouabain on the response of vascular smooth muscle to endothelium-derived relaxing factors released under basal conditions and on stimulation with acetylcholine or bradykinin. Bioassay rings of canine coronary artery (without endothelium) were superfused with perfusate from canine left circumflex coronary arteries with endothelium (donor arteries). During contractions of the bioassay ring evoked by prostaglandin F2 alpha, the relaxations caused by endothelium-derived relaxing factor(s), released under basal conditions or on exposure of the endothelial cells of the donor artery to maximally effective concentrations of acetylcholine, were reduced by incubation of the bioassay ring with ouabain. However, the relaxations evoked by infusion of bradykinin were not altered by incubation of the bioassay rings with ouabain. These experiments demonstrate the release of two endothelium-derived relaxing factors that can be distinguished using ouabain.

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Subarachnoid hemorrhage inhibition of endothelium-derived relaxing factor in rabbit basilar artery

Journal of Neurosurgery ◽

10.3171/jns.1988.69.2.0247 ◽

1988 ◽

Vol 69 (2) ◽

pp. 247-253 ◽

Cited By ~ 85

Author(s):

Kazuhiro Hongo ◽

Neal F. Kassell ◽

Tadayoshi Nakagomi ◽

Tomio Sasaki ◽

Tetsuya Tsukahara ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Basilar Artery ◽

Selective Inhibitor ◽

Isometric Tension ◽

The Other ◽

Content Type ◽

Relaxing Factor ◽

Endothelium Derived Relaxing Factor ◽

Fine Print

✓ Vascular contractions in response to KCl and serotonin (5-hydroxytryptamine, 5-HT) in rabbit basilar artery were studied in vitro using an isometric tension-measurement technique. Hemoglobin ( 10−5 M) markedly augmented contractions induced by 5-HT (10−9 to 10−6 M) and slightly augmented those induced by KCl (20 to 80 mM) in arteries with intact endothelium. On the other hand, the augmentation induced by hemoglobin was almost abolished in arteries that were chemically denuded of endothelial cells by pretreatment with saponin. Since hemoglobin is known to be a selective inhibitor of endothelium-derived relaxing factor (EDRF), it is possible that the augmentation of contraction by hemoglobin in endothelium-intact arteries was mediated via an inhibition of spontaneously released EDRF. The effect of subarachnoid hemorrhage (SAH) on spontaneously released EDRF was investigated by injecting 5 ml of blood into the cisterna magna and sacrificing the rabbits 2 days later. Arteries after SAH showed a significant reduction in hemoglobin-induced augmentation compared to that seen in control arteries with intact endothelium. This result suggests that spontaneously released EDRF is significantly reduced after SAH. It is concluded that EDRF is released spontaneously in the rabbit basilar artery and that inhibition of its release might be involved in pathogenesis of cerebral vasospasm.

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Lowering Po2 induces epithelium-dependent relaxation in isolated canine bronchi

AJP Cell Physiology ◽

10.1152/ajpcell.1989.257.5.c1034 ◽

1989 ◽

Vol 257 (5) ◽

pp. C1034-C1037 ◽

Cited By ~ 9

Author(s):

Y. S. Gao ◽

P. M. Vanhoutte

Keyword(s):

Methylene Blue ◽

Sodium Channels ◽

Respiratory Epithelium ◽

Isometric Tension ◽

Solution Temperature ◽

Reflex Mechanism ◽

Relaxing Factor ◽

Bronchial Lumen ◽

Endothelium Derived Relaxing Factor ◽

Local Reflex

This study was designed to investigate whether the respiratory epithelium can modulate the tone of the underlying smooth muscle in response to decreases in partial pressure of O2 (PO2). Canine bronchial segments with or without epithelium (diameter, 4-6 mm; length, 50-60 mm) were mounted in organ chambers and perfused intraluminally with modified Krebs-Ringer bicarbonate solution [temperature, 37 degrees C; PO2 varying from 600 (control) to 40 mmHg; PCO2, 36 mmHg]. Isometric tension was recorded by means of stirrups passed through the wall of the central part of the bronchial segment. During contractions to carbachol, the tissues with epithelium showed epithelium-dependent relaxations when the PO2 was decreased. The level of relaxation was dependent on the PO2. The epithelium-dependent relaxation could not be blocked by the following agents: indomethacin, methylene blue, propranolol, or tetrodotoxin (antagonists or blockers of cyclooxygenase, guanylate cyclase, beta-adrenoceptors, and sodium channels, respectively). The epithelium-dependent relaxation was not accompanied by the release of an assayable relaxing factor in the bronchial lumen. The experiments suggest that 1) lowering the PO2 induces the epithelium to release a relaxing factor(s), which is neither a product of cyclooxygenase nor endothelium-derived relaxing factor; 2) a local reflex mechanism is not involved in the phenomenon; and 3) the relaxing factor(s) either is not released into the bronchial lumen or, if it is, is catalyzed rapidly in the lumen on release.

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Proximal and distal dog coronary arteries respond differently to basal EDRF but not to NO

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.256.3.h828 ◽

1989 ◽

Vol 256 (3) ◽

pp. H828-H831 ◽

Cited By ~ 2

Author(s):

U. Hoeffner ◽

C. Boulanger ◽

P. M. Vanhoutte

Keyword(s):

Nitric Oxide ◽

Smooth Muscle ◽

Coronary Artery ◽

Sodium Nitroprusside ◽

Coronary Arteries ◽

Relaxing Factor ◽

Prostaglandin F2 Alpha ◽

Endothelium Derived Relaxing Factor

Experiments were designed to analyze the effects of endothelium-derived relaxing factor(s) (EDRF; released basally or on stimulation with acetylcholine) and nitric oxide (NO) on smooth muscle of coronary arteries of different diameter. During contractions of the bioassay ring evoked with prostaglandin F2 alpha, the relaxations caused by basal EDRF were greater in the distal than in the proximal coronary arteries, whereas there was no difference in response to the EDRF released by acetylcholine. During direct superfusion, NO caused similar relaxations in proximal and distal coronary artery rings. Optimal tension, prostaglandin F2 alpha-induced contractions, and relaxations caused by sodium nitroprusside were comparable in both preparations. In rings of proximal and distal coronary artery studied in organ chambers, acetylcholine caused comparable endothelium-dependent, whereas sodium nitroprusside and NO cause comparable endothelium-independent relaxations. These experiments indicate a difference in response of different-sized coronary arteries to basally released EDRF and suggest that the basally released factor differs from NO.

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Synthetic nitrovasodilators are effective, in vitro, in relaxing penile tissue from impotent men: the findings and their implications

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-014 ◽

1989 ◽

Vol 67 (1) ◽

pp. 78-81 ◽

Cited By ~ 21

Author(s):

Jeremy P. W. Heaton

Keyword(s):

Smooth Muscle ◽

Muscle Relaxation ◽

Venous Occlusion ◽

Isometric Tension ◽

Smooth Muscle Relaxation ◽

Clinical Criteria ◽

Erectile Tissue ◽

Relaxing Factor ◽

Endothelium Derived Relaxing Factor

Normal penile erectile function is dependent on arterial adequacy, appropriate venous occlusion, neurohumoral factors, and finally the relaxation of penile cavernous trabecular smooth muscle. The present experiments were designed to test whether compounds related to endothelium-derived relaxing factor have a role in penile smooth muscle relaxation and whether this role is preserved in clinically impotent tissue. Isometric tension experiments were conducted using strips of human tissue (appropriately obtained) from patients found to be impotent by clinical criteria. Glyceryl trinitrate and isosorbide dinitrate produced maximal relaxations of 66 and 63%, respectively, in tissues contracted with norepinephrine: 50% relaxation was observed at 6 × 10−7 and 8 × 10−5 M, respectively. The finding of a relaxant response to synthetic nitrovasodilators in "impotent" tissue implies that (i) complete end organ (smooth muscle) failure is not always, if ever, seen, (ii) endothelium-derived factors probably play a role in erectile tissue parallel with their role in other vascular tissues, (iii) more proximal factors may be responsible for clinical impotence, and (iv) synthetic nitrovasodilators may have a role in the therapy of clinical impotence.Key words: penis, erection, nitrovasodilators, endothelium-derived relaxing factor, human.

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The basal and stimulated release of the endothelium-derived relaxing factor from isolated pig coronary arteries does not interfere with the vascular release of superoxide

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/bf00169835 ◽

1994 ◽

Vol 349 (2) ◽

Cited By ~ 4

Author(s):

R.P. Brandes ◽

A. Dwenger ◽

A. M�gge

Keyword(s):

Coronary Arteries ◽

Relaxing Factor ◽

Endothelium Derived Relaxing Factor ◽

Pig Coronary Arteries

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Antagonists of EDRF attenuate acetylcholine-induced vasodilation in isolated hamster lungs

Journal of Applied Physiology ◽

10.1152/jappl.1992.72.6.2162 ◽

1992 ◽

Vol 72 (6) ◽

pp. 2162-2167 ◽

Cited By ~ 4

Author(s):

C. M. Tseng ◽

W. Mitzner

Keyword(s):

Methylene Blue ◽

Smooth Muscle ◽

Angiotensin Ii ◽

Krebs Solution ◽

Inhibitory Effects ◽

Relaxing Factor ◽

Prostaglandin F2 Alpha ◽

Pressor Responses

To evaluate the role of endothelium-dependent relaxing factor (EDRF) in acetylcholine- (ACh) induced vasodilation in the intact pulmonary circulation, we examined the effects of atropine and three EDRF antagonists that have been shown to be effective in vitro: nitro-L-arginine (NOARG), hemoglobin (Hb), and methylene blue (MB). We studied ACh-induced dilation after preconstriction with angiotensin II and prostaglandin F2 alpha (PGF2 alpha) in hamster lungs perfused with Krebs solution containing Ficoll (4 g/dl) and indomethacin (10 microM). In the constricted lungs with no blockers, infusion of ACh (1 microM) decreased the constriction by 67%, and this effect was completely abolished by atropine pretreatment (1 microM). Treatment of hamster lungs with each of the three EDRF blockers, NOARG (30 microM), Hb (10 microM), and MB (250 microM), augmented the pressor responses to angiotensin II and PGF2 alpha. However, NOARG and MB inhibited the ACh-induced dilation by 49 and 60%, respectively, without affecting vasodilatory responses to isoproterenol, an agent that relaxes vascular smooth muscle independent of EDRF synthesis. In contrast, Hb significantly inhibited both ACh- and isoproterenol-induced vasodilations. Because all these EDRF antagonists attenuated ACh-induced vasodilation in intact hamster lungs, we conclude that EDRF plays a role in this response. Nonselective inhibitory effects of Hb in hamster lungs, however, suggest that mechanisms other than inhibition of EDRF by this agent are also involved.

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Human basilar and middle cerebral arteries exhibit endothelium-dependent responses to peptides

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.267.3.h880 ◽

1994 ◽

Vol 267 (3) ◽

pp. H880-H886 ◽

Cited By ~ 2

Author(s):

H. Onoue ◽

N. Kaito ◽

M. Tomii ◽

S. Tokudome ◽

M. Nakajima ◽

...

Keyword(s):

Substance P ◽

Cerebral Arteries ◽

Isometric Tension ◽

Relaxing Factor ◽

Prostaglandin F2 Alpha ◽

Middle Cerebral Arteries ◽

Vasopressin Receptors ◽

Basilar Arteries ◽

Human Cadavers ◽

Endothelium Derived Relaxing Factor

We examined the activities of bradykinin, substance P, and vasopressin in isolated human cerebral arteries to better understand humoral control of cerebrovascular tone. Basilar and middle cerebral arteries were isolated from human cadavers during autopsy, and isometric tension was measured in helical strips of the arteries. Both bradykinin and substance P relaxed strips of both arteries precontracted with prostaglandin F2 alpha to similar extents. The relaxations induced by both peptides were abolished by removal of the vascular endothelium and were markedly reduced by pretreatment with NG-nitro-L-arginine, an inhibitor of endothelium-derived relaxing factor. Treatment with indomethacin, a cyclooxygenase inhibitor, did not attenuate the relaxations. These results indicate that the responses of human cerebral arteries to bradykinin and substance P are mediated by endothelium-derived relaxing factor. In contrast, vasopressin primarily produced endothelium-independent contractions in human cerebral arteries. Contractions of basilar arteries induced by vasopressin were much less than those of middle cerebral arteries. Two of eighteen basilar arteries, but none of the middle cerebral arteries, responded to vasopressin with endothelium-dependent relaxation. This suggests that the function of vasopressin receptors differs in basilar and middle cerebral arteries.

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