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.

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.

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.

scholarly journals Maternal nutrient restriction during pregnancy impairs an endothelium-derived hyperpolarizing factor-like pathway in sheep fetal coronary arteries

2014 ◽  
Vol 307 (2) ◽  
pp. H134-H142 ◽  
Author(s):  
Praveen Shukla ◽  
Srinivas Ghatta ◽  
Nidhi Dubey ◽  
Caleb O. Lemley ◽  
Mary Lynn Johnson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Coronary Arteries ◽  
National Research Council ◽  
Muscle Cells ◽  
Nutrient Restriction ◽  
Epoxyeicosatrienoic Acid ◽  
Coronary Smooth Muscle ◽  
Maternal Undernutrition ◽  
Current Activation

The mechanisms underlying developmental programming are poorly understood but may be associated with adaptations by the fetus in response to changes in the maternal environment during pregnancy. We hypothesized that maternal nutrient restriction during pregnancy alters vasodilator responses in fetal coronary arteries. Pregnant ewes were fed a control [100% U.S. National Research Council (NRC)] or nutrient-restricted (60% NRC) diet from days 50 to 130 of gestation (term = 145 days); fetal tissues were collected at day 130. In coronary arteries isolated from control fetal lambs, relaxation to bradykinin was unaffected by nitro-l-arginine (NLA). Iberiotoxin or contraction with KCl abolished the NLA-resistant response to bradykinin. In fetal coronary arteries from nutrient-restricted ewes, relaxation to bradykinin was fully suppressed by NLA. Large-conductance, calcium-activated potassium channel (BKCa) currents did not differ in coronary smooth muscle cells from control and nutrient-restricted animals. The BKCa openers, BMS 191011 and NS1619, and 14,15-epoxyeicosatrienoic acid [a putative endothelium-derived hyperpolarizing factor (EDHF)] each caused fetal coronary artery relaxation and BKCa current activation that was unaffected by maternal nutrient restriction. Expression of BKCa-channel subunits did not differ in fetal coronary arteries from control or undernourished ewes. The results indicate that maternal undernutrition during pregnancy results in loss of the EDHF-like pathway in fetal coronary arteries in response to bradykinin, an effect that cannot be explained by a decreased number or activity of BKCa channels or by decreased sensitivity to mediators that activate BKCa channels in vascular smooth muscle cells. Under these conditions, bradykinin-induced relaxation is completely dependent on nitric oxide, which may represent an adaptive response to compensate for the absence of the EDHF-like pathway.

14,15-Dihydroxyeicosatrienoic acid relaxes bovine coronary arteries by activation of KCa channels

2002 ◽  
Vol 282 (5) ◽  
pp. H1656-H1664 ◽  
Author(s):  
William B. Campbell ◽  
Christine Deeter ◽  
Kathryn M. Gauthier ◽  
Richard H. Ingraham ◽  
J. R. Falck ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Coronary Arteries ◽  
Epoxide Hydrolase ◽  
Muscle Cells ◽  
Kca Channels ◽  
Vasodilator Activity ◽  
Inside Out ◽  
Isolated Smooth Muscle Cells

Epoxyeicosatrienoic acids (EETs) cause vascular relaxation by activating smooth muscle large conductance Ca2+-activated K+ (KCa) channels. EETs are metabolized to dihydroxyeicosatrienoic acids (DHETs) by epoxide hydrolase. We examined the contribution of 14,15-DHET to 14,15-EET-induced relaxations and characterized its mechanism of action. 14,15-DHET relaxed U-46619-precontracted bovine coronary artery rings but was approximately fivefold less potent than 14,15-EET. The relaxations were inhibited by charybdotoxin, iberiotoxin, and increasing extracellular K+ to 20 mM. In isolated smooth muscle cells, 14,15-DHET increased an iberiotoxin-sensitive, outward K+ current and increased KCa channel activity in cell-attached patches and inside-out patches only when GTP was present. 14,15-[14C]EET methyl ester (Me) was converted to 14,15-[14C]DHET-Me, 14,15-[14C]DHET, and 14,15-[14C]EET by coronary arterial rings and endothelial cells but not by smooth muscle cells. The metabolism to 14,15-DHET was inhibited by the epoxide hydrolase inhibitors 4-phenylchalcone oxide (4-PCO) and BIRD-0826. Neither inhibitor altered relaxations to acetylcholine, whereas relaxations to 14,15-EET-Me were increased slightly by BIRD-0826 but not by 4-PCO. 14,15-DHET relaxes coronary arteries through activation of KCa channels. Endothelial cells, but not smooth muscle cells, convert EETs to DHETs, and this conversion results in a loss of vasodilator activity.

Extracellular calcium-dependent and -independent effects of adenosine in bovine coronary artery

1990 ◽  
Vol 68 (5) ◽  
pp. 608-613 ◽  
Author(s):  
Mudumbi V. Ramagopal ◽  
S. Jamal Mustafa
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Extracellular Calcium ◽  
Free Medium ◽  
Response Curves ◽  
Coronary Smooth Muscle ◽  
Calcium Dependent ◽  
Relaxation Responses ◽  
The Right

Adenosine relaxes the coronary arteries of various species through A2 receptors. The aim of the present investigation was to evaluate the relaxing effects of adenosine in relation to the role of calcium in bovine coronary arteries by studying the vasodilatory effect of adenosine in normal and calcium-free medium and on calcium-45 efflux into calcium-free medium. Acetylcholine (ACh) and norepinephrine (NE) were used to induce tone in coronary artery rings. Adenosine, 5′-(N-ethylcarboxamido)adenosine (NECA), and N6-(L-phenylisopropyl)adenosine (L-PIA) produced concentration-dependent relaxations of the coronary artery rings. Both in normal and calcium-free medium, the order of potency for adenosine analogs (NECA > L-PIA > adenosine) was similar and 8-phenyltheophylline antagonized the relaxation responses to adenosine and its analogs. Removal of extracellular calcium shifted the concentration–response curves to the right in a parallel fashion, slowed the rate of relaxation, and in NE contracted rings reduced the maximum responses for adenosine and its analogs. In calcium-free medium, adenosine was without an effect on calcium-45 efflux in the presence of ACh. However, adenosine inhibited the stimulated calcium-45 efflux induced by NE. The data suggest that the vasodilatory action of adenosine in bovine coronary smooth muscle has both extracellular calcium-dependent and -independent components.Key words: adenosine receptors, calcium, coronary circulation, vascular smooth muscle, acetylcholine, norepinephrine.

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.

Endothelium-dependent vasodilation of canine coronary collateral vessels

1991 ◽  
Vol 261 (6) ◽  
pp. H1797-H1801 ◽  
Author(s):  
N. M. Flynn ◽  
D. Kenny ◽  
L. R. Pelc ◽  
D. C. Warltier ◽  
Z. J. Bosnjak ◽  
...  
Keyword(s):  
Sodium Nitroprusside ◽  
Coronary Arteries ◽  
Maximal Response ◽  
Small Arteries ◽  
Relaxing Factor ◽  
Coronary Collateral ◽  
Prostaglandin F2 Alpha ◽  
Collateral Vessels ◽  
Endothelium Dependent Relaxation

The objective of this study was to determine whether endothelium-mediated relaxation occurs in canine coronary collateral vessels. Responses to endothelium-dependent vasodilators in coronary collateral vessels (250-350 microns) were compared with those obtained in normal native coronary arteries of similar size. Rings of small arteries and collateral vessels were suspended in baths, and tension was recorded. All rings were constricted with prostaglandin F2 alpha (3 microM) and subsequently exposed to cumulative concentrations of acetylcholine or bradykinin. In separate experiments, the procedure was repeated in the presence of 300 microM NG-monomethyl-L-arginine (L-NMMA) to inhibit endothelium-mediated vasodilation. Endothelium-dependent relaxation was further studied in the presence of indomethacin, and endothelium-independent relaxation was examined with sodium nitroprusside. Acetylcholine and bradykinin relaxed both normal native and collateral rings. In preconstricted small arteries and collateral vessels the concentration at 50% of maximal response of acetylcholine was 85.5 +/- 19.5 and 61.0 +/- 14.0 microns, and bradykinin was 11.9 +/- 7.4 and 10.7 +/- 2.1 microns, respectively. L-NMMA attenuated the response to acetylcholine and bradykinin in both groups. The results indicate that endothelium is present and functional in canine coronary collateral vessels. Both small coronary arteries and collateral vessels are equally responsive to endothelium-dependent vasodilators and inhibition of endothelium-dependent relaxing factor.

Sign in / Sign up

Export Citation Format

Share Document