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.

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.

Evidence against KATP channel involvement in adenosine receptor-mediated dilation of epicardial vessels

1994 ◽  
Vol 267 (2) ◽  
pp. H716-H724 ◽  
Author(s):  
S. R. Makujina ◽  
H. A. Olanrewaju ◽  
S. J. Mustafa
Keyword(s):  
Adenosine Receptor ◽  
Katp Channel ◽  
Response Curve ◽  
Channel Blocker ◽  
Rightward Shift ◽  
Prostaglandin F2 Alpha ◽  
Phenylisopropyl Adenosine ◽  
Concentration Response Curve ◽  
Channel Activator

The purpose of this study was to determine whether ATP-glyburide-sensitive K+ (KATP-glyburide) channels are involved in the adenosine-induced vasorelaxation of porcine and canine epicardial vessels in vitro. Adenosine and its analogues, 2-chloroadenosine (CAD), 5'-N-ethylcarboxamidoadenosine (NECA), R-N6-(2-phenylisopropyl)adenosine (R-PIA), N6-cyclopentyladenosine (CPA), N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)]adenosine (DPMA), 2-phenylaminoadenosine (CV-1808), 2-[m-(carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS-22988), 2-[(2-cyclohexylethyl)amino]adenosine (CGS-22492), 2-[(p-amino)phenethylamino]adenosine (APE), and 2-(1-octynyl)adenosine (YT-146) (10 nM-100 microM), produced concentration-dependent relaxations in endothelium-intact and -denuded arterial ring segments contracted with 30 mM KCl, 10 nM endothelin-1, or 10 microM prostaglandin F2 alpha. Sodium nitroprusside (SNP; 1 nM-10 microM) and KATP-channel activator, pinacidil (10 nM-10 microM), also produced similar vasodilatory responses. Glyburide, a KATP-channel blocker, caused a rightward shift of the concentration-response curve to pinacidil but did not alter the responses elicited by SNP or adenosine and its analogues. The data suggest that KATP-glyburide channels are not involved in the mechanism whereby adenosine and its analogues elicit their vasorelaxant response in isolated porcine or canine epicardial vessels.

Adenine nucleotides, serotonin, and endothelium-dependent relaxations to platelets

1985 ◽  
Vol 248 (3) ◽  
pp. H389-H395 ◽  
Author(s):  
D. S. Houston ◽  
J. T. Shepherd ◽  
P. M. Vanhoutte
Keyword(s):  
Coronary Arteries ◽  
Salt Solution ◽  
Adenine Nucleotides ◽  
Adenosine Diphosphate ◽  
Physiological Salt Solution ◽  
Contractile Effect ◽  
Prostaglandin F2 Alpha ◽  
Endothelium Dependent Relaxation ◽  
Serotonergic Antagonist

Aggregating platelets cause an endothelium-dependent relaxation of isolated contracted canine coronary arteries. The role of adenine nucleotides and of 5-hydroxytryptamine in causing this relaxation was determined. Rings of these arteries were suspended in organ chambers filled with physiological salt solution and contracted with prostaglandin F2 alpha. Adenosine diphosphate relaxed rings with intact endothelium but had no effect on endothelium-denuded rings. The relaxation was attenuated by the enzyme, apyrase, which hydrolyzes adenosine tri- and diphosphate. 5-Hydroxytryptamine (5-HT) exerted a direct contractile effect mediated by the endothelium. The latter was prevented by the 5-HT1 serotonergic antagonist, methiothepin, but not by the 5-HT2 serotonergic antagonist, ketanserin. The endothelially mediated relaxation to aggregating platelets was prevented by apyrase but not by methiothepin or ketanserin. Responses to platelets were unaltered by the inhibitor of cyclooxygenase, meclofenamate. These experiments demonstrate the key role of adenine nucleotides in mediating the endothelium-dependent relaxation of canine coronary arteries to aggregating platelets.

Enhanced β-receptor-mediated vasorelaxation in hypoxic porcine coronary artery

1999 ◽  
Vol 277 (4) ◽  
pp. H1447-H1452 ◽  
Author(s):  
Satoru Fukuda ◽  
Takashi Toriumi ◽  
Hui Xu ◽  
Hidenori Kinoshita ◽  
Hironobu Nishimaki ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Coronary Arteries ◽  
Response Curve ◽  
Dibutyryl Camp ◽  
Camp Content ◽  
Porcine Coronary Artery ◽  
Vasodilatory Response ◽  
High Concentrations ◽  
Β Receptor ◽  
Concentration Response Curve

To investigate the β-adrenoceptor-mediated responses in hypoxic coronary arteries, we studied the effect of isoproterenol (Iso) on isolated porcine coronary arteries contracted with endothelin-1 in media aerated with 0, 5, 7.5, and 95% O2. The concentration-response curve of Iso was significantly shifted to the left by hypoxia (0 and 5% O2). In oxygenated and hypoxic arteries, 3 × 10−8, 10−6, and 10−5 M Iso significantly increased the contents of cAMP. However, there was no difference in the increases of cAMP content induced by 3 × 10−8 M Iso between oxygenated and hypoxic arteries. The content of cAMP induced by high concentrations of Iso (10−6and 10−5 M) was significantly larger in hypoxic than in oxygenated arteries. Furthermore, the potentiation by hypoxia of the Iso-induced vasorelaxation was inhibited by glibenclamide and depolarization by KCl, but not by removal of endothelium and indomethacin. The vasodilatory response to forskolin and dibutyryl cAMP was unaffected by hypoxia. We conclude that activation of the ATP-sensitive K+ channel may account for the potentiation of the response to Iso in hypoxic coronary arteries.

LTD4 induces hyperresponsiveness to histamine in bovine airway smooth muscle: role of SR-ATPase Ca2+ pump and tyrosine kinase

2005 ◽  
Vol 288 (1) ◽  
pp. L84-L92 ◽  
Author(s):  
Verónica Carbajal ◽  
Mario H. Vargas ◽  
Edgar Flores-Soto ◽  
Erasmo Martínez-Cordero ◽  
Blanca Bazán-Perkins ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Tyrosine Kinase ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Response Curve ◽  
Cyclopiazonic Acid ◽  
Extracellular Signal ◽  
Intracellular Ca ◽  
Concentration Response Curve

Airway hyperresponsiveness is a key feature of asthma, but its mechanisms remain poorly understood. Leukotriene D4 (LTD4) is one of the few molecules capable of producing airway hyperresponsiveness. In this study, LTD4, but not leukotriene C4 (LTC4), produced a leftward displacement of the concentration-response curve to histamine in bovine airway smooth muscle strips. Neither LTC4 nor LTD4 modified the concentration-response curve to carbachol. In simultaneous measurements of intracellular Ca2+ ([Ca2+]i) and contraction, histamine or carbachol produced a transient Ca2+ peak followed by a plateau, along with a contraction. LTD4 increased the histamine-induced transient Ca2+ peak and contraction but did not modify responses to carbachol. Enhanced responses to histamine induced by LTD4 were not modified by staurosporine or chelerythrine but were abolished by genistein. Western blot showed that carbachol, but not histamine, caused intense phosphorylation of extracellular signal-regulated kinase 1/2 and that LTD4 significantly enhanced the phosphorylation induced by histamine, but not by carbachol. L-type Ca2+ channel participation in the hyperresponsiveness to histamine was discarded because LTD4 did not modify the [Ca2+]i changes induced by KCl. In tracheal myocytes, LTD4 enhanced the transient Ca2+ peak induced by histamine (but not by carbachol) and the sarcoplasmic reticulum (SR) Ca2+ refilling. Genistein abolished this last LTD4 effect. Partial blockade of the SR-ATPase Ca2+ pump with cyclopiazonic acid reduced the Ca2+ transient peak induced by histamine but not by carbachol. These results suggested that LTD4 induces hyperresponsiveness to histamine through activation of the tyrosine kinase pathway and an increasing SR-ATPase Ca2+ pump activity. L-type Ca2+ channels seemed not to be involved in this phenomenon.

Characteristics of canine coronary resistance arteries: importance of endothelium

1989 ◽  
Vol 257 (2) ◽  
pp. H603-H610 ◽  
Author(s):  
P. R. Myers ◽  
P. F. Banitt ◽  
R. Guerra ◽  
D. G. Harrison
Keyword(s):  
Coronary Arteries ◽  
Vascular Reactivity ◽  
Maximum Response ◽  
Coronary Resistance ◽  
Resistance Arteries ◽  
Resistance Vessels ◽  
Dose Dependent ◽  
Large Coronary Arteries

Canine coronary resistance vessels were studied in vitro to examine the role of the endothelium in modulating responses to acetylcholine, vasopressin, and thrombin and to compare these responses to those found in large epicardial vessels. Acetylcholine had no effect on passively distended microvessels; however, after preconstriction with the thromboxane analogue, U 46619 caused dose-dependent vasodilation [50% effective concentration (EC50), 0.05 microM; maximum response, 97.9 +/- 2.1% relaxation]. Large epicardial arterial rings studied in organ chambers similarly relaxed to acetylcholine (EC50, 0.07 microM; maximum response, 79 +/- 5% relaxation). Hemoglobin was utilized to inactivate endothelium-derived relaxing factor (EDRF), resulting in reversal of acetylcholine vasodilation in both the microvessels (92 +/- 3.2% reversal) and the large epicardial vessels (117 +/- 9%). Hemoglobin had no effect on passively distended or preconstricted microvessels. Vasopressin constricted resistance vessels by 22.3 +/- 5.9 microns at 500 microU/ml. Hemoglobin potentiated this response by 100%, suggesting that vasopressin elicited EDRF release. In large coronary arteries, however, vasopressin elicited endothelium-dependent dilation with maximal relaxation of 36 +/- 9% at 3,000 microU/ml. Thrombin produced endothelium-dependent relaxation of large epicardial arterial rings but only constricted coronary microvessels. The response to thrombin was not altered by hemoglobin. This study demonstrates that the endothelium of coronary microvessels, like that of larger vessels, importantly modulates vascular reactivity to selected agents. Furthermore, major differences exist between large and small coronary arteries in their response to vasopressin and thrombin.

FEEDBACK CONTROL OF FSH IN THE MALE: ROLE OF OESTROGEN

1973 ◽  
Vol 74 (3) ◽  
pp. 449-460 ◽  
Author(s):  
Patrick C. Walsh ◽  
Ronald S. Swerdloff ◽  
William D. Odell
Keyword(s):  
Luteinizing Hormone ◽  
Follicle Stimulating Hormone ◽  
Oestrogen Therapy ◽  
Serum Concentrations ◽  
Elderly Men ◽  
Normal Range ◽  
Oestrogen Treatment ◽  
Serum Lh ◽  
Higher Doses

ABSTRACT Serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay in a group of elderly men following castration and oestrogen therapy. Prior to orchiectomy, mean serum concentrations of LH and FSH were within the normal range. Two days following castration, serum LH concentrations increased in all eight patients; higher levels of LH were subsequently measured in all but one patient after periods of time ranging from 49 to 210 days. Serum FSH levels, measured in three patients following castration, increased in a pattern parallel to LH changes. Ethinyl oestradiol (EOe) in doses ranging from 5 to 300 μg/day was administered to ten men who had been castrated 3 to 72 months earlier. Oestrogen treatment suppressed both LH and FSH in a parellel manner in nine of ten patients. LH was first suppressed to intact levels in one of eight patients treated with 20 μg/day of EOe, in two of six patients treated with 50 μg/day, and in one patient by 80 μg/day. FSH was not suppressed to precastration levels until 50 μg/day of EOe was administered; this dose suppressed three of six patients. Higher doses of EOe (150–300 μg/day) suppressed both LH and FSH to levels below the sensitivity of the assay. These data fail to demonstrate any differential effect of oestrogen on LH and FSH release.

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