Hypoxic contraction of canine coronary arteries: role of endothelium and cGMP

1991 ◽  
Vol 261 (6) ◽  
pp. H1769-H1777 ◽  
Author(s):  
T. Graser ◽  
P. M. Vanhoutte
Keyword(s):  
Methylene Blue ◽  
Smooth Muscle ◽  
Coronary Arteries ◽  
Cgmp Level ◽  
Moderate Increase ◽  
Prostaglandin F2 Alpha ◽  
Canine Coronary Artery ◽  
Ly 83583 ◽  
Transient Relaxation

The effect of severe hypoxia in quiescent or contracted (prostaglandin F2 alpha) canine coronary artery rings with and without endothelium was studied. Hypoxia induced an initial transient relaxation followed by a sustained contraction. The hypoxic contraction in quiescent rings was comparable in rings with and without endothelium. The facilitation of the contraction to prostaglandin F2 alpha was more pronounced in rings with endothelium. Increasing the level of contractions by augmenting the contraction of prostaglandin F2 alpha potentiated the hypoxic contraction in rings with endothelium only. Methylene blue, LY 83583, and nitro-L-arginine reversed the hypoxic facilitation in contracted rings into relaxation, whereas M&B 22948 augmented it. In quiescent coronary preparations, methylene blue reversed the hypoxic contraction into relaxation in preparations with and without endothelium, whereas nitro-L-arginine had the same effect in vessels with endothelium only. SIN-1, nitroglycerin, and dibutyryl guanosine 3',5'-cyclic monophosphate (cGMP) unmasked hypoxic facilitation in rings without endothelium. This was not observed with isoproterenol. The measurement of the level of cGMP revealed an increased level in rings with endothelium compared with those without endothelium under control oxygenation. This difference disappeared during hypoxia due to a decrease of cGMP content in vessels with endothelium. The results suggest that a moderate increase of the cGMP level in vascular smooth muscle is a prerequisite for the occurrence of hypoxia-induced facilitation in contracted canine coronary arteries.

Canine arteries release two different endothelium-derived relaxing factors

1989 ◽  
Vol 257 (1) ◽  
pp. H330-H333 ◽  
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.

Inhibitors of cyclooxygenase augment serotonergic responsiveness in canine coronary arteries

1988 ◽  
Vol 255 (5) ◽  
pp. H1032-H1035
Author(s):  
G. Blaise ◽  
A. Iqbal ◽  
P. M. Vanhoutte
Keyword(s):  
Coronary Arteries ◽  
Response Curve ◽  
Coronary Smooth Muscle ◽  
Prostaglandin F2 Alpha ◽  
Secondary Relaxations ◽  
Canine Coronary Artery ◽  
Higher Doses ◽  
Large Coronary Arteries ◽  
Concentration Response Curve

Experiments were designed to determine the role of products of cyclooxygenase in contractions of coronary smooth muscle evoked by serotonin. Rings of canine coronary artery without endothelium were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Serotonin caused concentration-dependent contractions followed by secondary relaxations at higher doses. Indomethacin and meclofenamate augmented both the contraction and the relaxation. Indomethacin did not affect contractions evoked by increasing concentrations of either phenylephrine, prostaglandin F2 alpha, or potassium chloride. Propranolol did not affect the concentration-response curve to serotonin under control conditions; it prevented the facilitated contraction to the monoamine but not the augmented secondary relaxation caused by the inhibitors of cyclooxygenase. These results suggest that endogenous prostanoids simultaneously inhibit the contractile process and brake relaxations induced by higher concentrations of serotonin. As a consequence, inhibitors of prostanoid formation facilitate the vasospastic component of the response to the monoamine in large coronary arteries. For unknown reasons, propranolol prevents this facilitation.

5-Hydroxytryptamine can mediate endothelium-dependent relaxation of coronary arteries

1983 ◽  
Vol 245 (6) ◽  
pp. H1077-H1080 ◽  
Author(s):  
R. A. Cohen ◽  
J. T. Shepherd ◽  
P. M. Vanhoutte
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Coronary Arteries ◽  
Inhibitory Action ◽  
Thromboxane A2 ◽  
Coronary Smooth Muscle ◽  
Serotonergic Receptors ◽  
Prostaglandin F2 Alpha ◽  
Canine Coronary Artery ◽  
Endothelium Dependent Relaxation

5-Hydroxytryptamine caused contractions of isolated canine coronary artery rings. These contractions were larger in the absence of the endothelium, whereas those caused by phenylephrine, potassium chloride, and prostaglandin F2 alpha were not. When coronary arteries were contracted with prostaglandin F2 alpha, 5-hydroxytryptamine caused relaxation in some rings with endothelium but only further contraction in all rings without endothelium. The inhibitory action of 5-hydroxytryptamine mediated by the endothelium was unaffected by blockade of monoamine oxidase or cyclooxygenase. In rings with endothelium, aggregating platelets, which released 5-hydroxytryptamine and thromboxane A2, caused relaxation. The relaxations caused by 5-hydroxytryptamine and aggregating platelets were antagonized by methysergide but not by ketanserin. These observations suggest that the response to 5-hydroxytryptamine is the net result of a direct contractile action on coronary smooth muscle and an inhibitory action mediated by the endothelium. In some vessels the endothelium-dependent inhibitory responses to aggregating platelets may be mediated in part by released 5-hydroxytryptamine. The serotonergic receptors on endothelial cells may be of a different subtype than those mediating contractions of the smooth muscle cells.

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

1992 ◽  
Vol 72 (6) ◽  
pp. 2162-2167 ◽  
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.

Melatonin potentiates contractile responses to serotonin in isolated porcine coronary arteries

2001 ◽  
Vol 280 (1) ◽  
pp. H76-H82 ◽  
Author(s):  
Qiong Yang ◽  
Elizabeth Scalbert ◽  
Philippe Delagrange ◽  
Paul M. Vanhoutte ◽  
Stephen T. O'Rourke
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Coronary Arteries ◽  
Isometric Tension ◽  
Maximal Response ◽  
Melatonin Receptor ◽  
Vasomotor Tone ◽  
Vasoconstrictor Response ◽  
Coronary Vasomotor Tone

The present study was designed to determine the effects of melatonin on coronary vasomotor tone. Porcine coronary arteries were suspended in organ chambers for isometric tension recording. Melatonin (10−10-10−5 M) itself caused neither contraction nor relaxation of the tissues. Serotonin (10−9-10−5 M) caused concentration-dependent contractions of coronary arteries, and in the presence of melatonin (10−7 M) the maximal response to serotonin was increased in rings with but not without endothelium. In contrast, melatonin had no effect on contractions produced by the thromboxane A2 analog U-46619 (10−10-10−7 M). The melatonin-receptor antagonist S-20928 (10−6 M) abolished the potentiating effect of melatonin on serotonin-induced contractions in endothelium-intact coronary arteries, as did treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10−5 M), methylene blue (10−5 M), or NG -nitro-l-arginine (3 × 10−5 M). In tissues contracted with U-46619, serotonin caused endothelium-dependent relaxations that were inhibited by melatonin (10−7 M). Melatonin also inhibited coronary artery relaxation induced by sodium nitroprusside (10−9-10−5 M) but not by isoproterenol (10−9-10−5 M). These results support the hypothesis that melatonin, by inhibiting the action of nitric oxide on coronary vascular smooth muscle, selectively potentiates the vasoconstrictor response to serotonin in coronary arteries with endothelium.

Isolated human coronary arteries in response to vasoconstrictor substances

1983 ◽  
Vol 245 (6) ◽  
pp. H937-H941 ◽  
Author(s):  
N. Toda
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Muscarinic Receptors ◽  
Coronary Arteries ◽  
Distal Portion ◽  
Alpha Adrenoceptors ◽  
Prostaglandin F2 Alpha ◽  
Arterial Contraction ◽  
Human Arteries ◽  
Contraction And Relaxation

In helical strips of human epicardial coronary arteries, norepinephrine produced a concentration-related contraction; the contractions relative to those induced by 30 mM K+ were greater in the proximal portion of the arteries than in the distal portion. The amine-induced contraction was suppressed by treatment with phentolamine. Acetylcholine contracted human coronary arteries but, in contrast, relaxed the monkey coronary arteries (both freshly excised and cadaver) previously contracted with prostaglandin F2 alpha. Both the contraction and relaxation induced by acetylcholine were suppressed by atropine. Removal of the endothelium abolished the relaxation of monkey arteries but did not significantly alter the contraction of human arteries. Human coronary arteries responded to histamine with contractions, which were reversed to relaxations following treatment with chlorpheniramine. It is concluded that, as far as the portions of human coronary arteries used in the present study are concerned, the arterial contraction mediated via alpha-adrenoceptors is inversely related to the distance from the coronary artery orifice. Acetylcholine produces contractions of human coronary arteries, possibly due to activation of muscarinic receptors on smooth muscle cells. Histamine-induced contractions appear to be mediated via H1-receptors.

Effects of hydrogen peroxide on the responsiveness of isolated canine bronchi: role of prostaglandin E2 and I2

1992 ◽  
Vol 263 (3) ◽  
pp. L402-L408 ◽  
Author(s):  
Y. Gao ◽  
P. M. Vanhoutte
Keyword(s):  
Hydrogen Peroxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Prostaglandin E2 ◽  
Respiratory Epithelium ◽  
Isometric Tension ◽  
Third Order ◽  
Bronchial Smooth Muscle ◽  
Cyclic Monophosphate

The present study was design to determine the role of prostaglandin E2 and I2 in the responses of isolated canine airways to H2O2. Rings of canine third-order bronchi, some of which had undergone mechanical denudation of the epithelium, were suspended in organ chambers; isometric tension was recorded. During contractions to acetylcholine, H2O2 induced concentration-dependent relaxations. The relaxations were attenuated significantly by indomethacin, acetylsalicylic acid, and methylene blue. H2O2 increased the release of prostaglandin E2 and 6-keto-prostaglandin F1 alpha and the content of adenosine 3',5'-cyclic monophosphate (cAMP). These effects were abolished by indomethacin or methylene blue. H2O2 did not affect the content of guanosine 3',5'-cyclic monophosphate significantly. These observations suggest that 1) H2O2 relaxes canine bronchial smooth muscle and 2) elevation of tissue content of cAMP induced by prostaglandin E2 and I2 may be involved. These phenomena did not appear to be modulated by the respiratory epithelium, since H2O2-induced relaxations and increases in the release of PGE2 and 6-ketoprostaglandin F1 alpha were similar in preparations with and without epithelium. However, after treatment with methylene blue, H2O2 induced contractions only in preparations with epithelium. These epithelium-dependent contractions were not affected by inhibitors of cyclooxygenase and lipoxygenase.

cGMP mediates the desensitization to bradykinin in isolated canine coronary arteries

1995 ◽  
Vol 268 (2) ◽  
pp. H865-H870 ◽  
Author(s):  
L. Olmos ◽  
J. V. Mombouli ◽  
S. Illiano ◽  
P. M. Vanhoutte
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Coronary Arteries ◽  
No Synthase ◽  
Cyclic Monophosphate ◽  
Prostaglandin F2 Alpha ◽  
Relaxation Curves ◽  
Synthase Inhibitor ◽  
The Right ◽  
Selective Impairment

The relaxation to bradykinin in canine coronary arteries is mediated by endothelium-derived nitric oxide (NO) and hyperpolarizing factor (EDHF). Desensitization to the kinin was induced by incubation of canine coronary arteries with endothelium with 10(-8) M bradykinin for 30 min. After washout, tissues were contracted with prostaglandin F2 alpha, and concentration-relaxation curves to bradykinin were obtained in control and desensitized arteries treated with indomethacin. After desensitization, there was a shift to the right of the concentration-relaxation curves to bradykinin. However, the elevation in guanosine 3',5'-cyclic monophosphate (cGMP) levels evoked by bradykinin was similar in both groups of tissues. The curves to bradykinin obtained in the presence of NG-nitro-L-arginine (an NO synthase inhibitor) were depressed, whereas those obtained in arteries contracted with potassium (to eliminate the EDHF-mediated relaxation) were not affected by the desensitization. Addition of NG-nitro-L-arginine, oxyhemoglobin, or methylene blue before the desensitization procedure preserved, whereas 3-morpholinosydnonimine (SIN-1, a donor of NO) and 8-bromoguanosine 3',5'-cyclic monophosphate impaired, the EDHF-mediated relaxation to bradykinin. Thus the selective impairment of the EDHF-dependent relaxation to bradykinin may be mediated by NO, acting mainly through increased production of cGMP.

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

1994 ◽  
Vol 266 (3) ◽  
pp. H874-H880 ◽  
Author(s):  
T. Murohara ◽  
K. Kugiyama ◽  
M. Ohgushi ◽  
S. Sugiyama ◽  
H. Yasue
Keyword(s):  
Methylene Blue ◽  
Cigarette Smoke ◽  
Coronary Arteries ◽  
Cigarette Smoke Extract ◽  
Isometric Tension ◽  
Relaxing Factor ◽  
Prostaglandin F2 Alpha ◽  
Endothelium Derived Relaxing Factor ◽  
Pig Coronary Arteries

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.

Role of cGMP mechanisms in response of rat pulmonary arteries to hypoxia

1992 ◽  
Vol 263 (1) ◽  
pp. H141-H146 ◽  
Author(s):  
R. Mathew ◽  
H. A. Omar ◽  
P. D. Cherry ◽  
M. H. Gewitz ◽  
M. S. Wolin
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Arteries ◽  
Phosphodiesterase Inhibitor ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Ly 83583 ◽  
Endothelium Dependent Relaxation ◽  
Guanylate Cyclase Activation ◽  
Isolated Rat

We have demonstrated previously that in response to hypoxia, isolated rat pulmonary arteries show an initial endothelium-dependent relaxation followed by an endothelium-independent transient contraction. In the presence of increased extracellular Ca2+, both of these responses were enhanced in endothelium-intact arteries. Nitro-L-arginine, a blocker of the biosynthesis of endothelium-derived relaxing factor (EDRF), abolished the initial endothelium-dependent relaxation and Ca(2+)-induced enhancement of hypoxic contraction in endothelium-intact arteries but did not alter responses in endothelium-denuded vessels. Inhibition of prostaglandin formation with indomethacin had no effect on the hypoxia-elicited responses. Preincubation with LY 83583, an inhibitor of guanylate cyclase activation, abolished the initial hypoxia-elicited relaxation and subsequent contraction. M & B 22948, a guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor, decreased tone under O2 but not under N2, causing an apparent enhancement of the contraction to hypoxia. Thus the modulation of hypoxic responses by the endothelium is dependent on changes in EDRF production, and a decrease in smooth muscle cGMP not involving an EDRF mechanism appears to mediate the endothelium-independent hypoxic contraction observed in the isolated rat pulmonary artery.

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