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European Journal of Pharmacology Jun 1999The mechanism of Hypoxic Pulmonary Vasoconstriction is unknown. The role of endothelin-1 in hypoxic pulmonary vasoconstriction was studied in precontracted small and...
The mechanism of Hypoxic Pulmonary Vasoconstriction is unknown. The role of endothelin-1 in hypoxic pulmonary vasoconstriction was studied in precontracted small and large pulmonary arteries using the endothelin ETA receptor antagonist sodium-2-benzol [1,3]dioxol-5-yl-4-(4-methoxyphenyl)-4-oxo-3-(3,4,5-trimethoxy-ben zyl)-but-2-enoate (CI-1020). Small rat pulmonary arteries exhibit a mixed endothelin ETA receptor and endothelin ETB2 receptor population whereas large rat pulmonary arteries contain only endothelin ETA receptors. CI-1020 inhibited endothelin-1 in small vessels via endothelin ETA receptor blockade (1 and 10 microM) and at high concentrations via endothelin ETA receptor and endothelin ETB2 receptor blockade (100 microM). CI-1020 (0.01, 0.1 and 1 microM) inhibited endothelin-1 in large vessels via endothelin ETA receptor blockade alone. CI-1020 (1, 10 and 100 microM) significantly reduced hypoxic pulmonary vasoconstriction in small vessels, by -9.8+/-1.4, -9.2+/-2.3 and -8.0+/-1.7% 80 mM K+, respectively, compared to +2.5+/-4.2% with vehicle (P < 0.05). CI-1020 (0.01, 0.1 and 1 microM) had no significant effect upon hypoxic pulmonary vasoconstriction in large vessels. In small, but not large, pulmonary arteries hypoxic pulmonary vasoconstriction is due in part to the action of endothelin-1 at the endothelin ETA receptor.
Topics: Animals; Dioxoles; Dose-Response Relationship, Drug; Endothelin Receptor Antagonists; Endothelin-1; Hypoxia; In Vitro Techniques; Male; Pulmonary Artery; Rats; Rats, Wistar; Receptor, Endothelin A; Vasoconstriction
PubMed: 10422781
DOI: 10.1016/s0014-2999(99)00300-3 -
FASEB Journal : Official Publication of... Mar 1995The present study in isolated rat lungs demonstrates that nitric oxide gas (.NO, 70 nM) added to the perfusate containing a small amount of hemolysate [175 microliters...
The present study in isolated rat lungs demonstrates that nitric oxide gas (.NO, 70 nM) added to the perfusate containing a small amount of hemolysate [175 microliters of lysed red blood cells (RBC) per 50 ml of Earle's balanced salt solution (EBSS)] triggered profound and sustained vasoconstriction. Vasoconstriction was not observed when .NO was added to lungs perfused with washed intact rat or human RBC or with oxyhemoglobin (Hgb 20 microM). The presence of hemolysate in the perfusate also caused vasoconstriction in response to n-acetylcysteine (50 microM), glutathione (10(-4) M), or ascorbic acid (10(-4) M) and potentiated greatly the vasoconstrictor response to 5 mM KCl. Not only .NO, but also nitroprusside (SNP) or L-arginine and paradoxically three .NO synthesis inhibitors, including N-monomethyl L-arginine, L-NAME, and nitroblue tetrazolium, which have different mechanisms of action, each caused in the presence of hemolysate large vasoconstrictive responses. Hemolysate itself enhanced O2 consumption by slices of lung; no effects of this dose of .NO on lung slice respiration were seen in the absence of hemolysate. Both Hgb and hemolysate lowered perfusate cGMP levels to the same degree suggesting that the vasoconstrictive response was not due to unique effects of hemolysate on guanylyl cyclase. Addition of superoxide dismutase (SOD) and catalase (CAT) to the hemolysate containing perfusate, or addition of a cyclooxygenase or 5-lipoxygenase inhibitor, virtually abolished the .NO induced vasoconstriction. The latter data are consistent with the concept that exposure of the vasculature to hemolysate may result in the formation of peroxynitrite. However, SOD and CAT did not abolish the pulmonary vasoconstriction induced by L-arginine or by NAC. Our data indicate that hemolysate has profound effects on lung vessel tone regulation and on lung tissue mitochondrial function, yet the precise molecular mechanisms responsible for the action of hemolysate are likely to be very complex.
Topics: Animals; Arginine; Catalase; Cyclic GMP; Dialysis; Ethylmaleimide; Hemolysis; In Vitro Techniques; Indoles; Lung; Meclofenamic Acid; Nitric Oxide; Nitroprusside; Oxygen Consumption; Perfusion; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Vasoconstriction
PubMed: 7896007
DOI: 10.1096/fasebj.9.5.7896007 -
Circulation Mar 1993The effects of cocaine on the coronary circulation were examined in conscious dogs chronically instrumented to measure arterial and left ventricular pressures, coronary... (Comparative Study)
Comparative Study
BACKGROUND
The effects of cocaine on the coronary circulation were examined in conscious dogs chronically instrumented to measure arterial and left ventricular pressures, coronary blood flow, and arterial and coronary sinus oxygen content.
METHODS AND RESULTS
With heart rate held constant, the peak effects of cocaine (1 mg/kg i.v.) occurred within 2 minutes, when mean arterial pressure increased by 42 +/- 5 mm Hg, coronary blood flow increased by 13 +/- 3%, and coronary vascular resistance increased by 24 +/- 3%. The arterial oxygen content increased significantly (by 2.8 +/- 0.3 vol%), the arterial-coronary sinus oxygen difference increased by 2.5 +/- 0.6 vol%, and myocardial oxygen consumption increased by 41 +/- 9%. The increase in coronary vascular resistance induced by cocaine was attenuated (p < 0.05) in the presence of cholinergic blockade (12 +/- 3%) despite a similar increase in MVO2 (49 +/- 8%). The increase in coronary vascular resistance was enhanced (p < 0.05) in the presence of beta-adrenergic receptor blockade (46 +/- 8%), whereas the MVO2 response was less (28 +/- 3%). Again, the addition of cholinergic blockade to beta-blockade attenuated the increase in coronary vascular resistance (23 +/- 6%) without affecting the increase in MVO2 (25 +/- 4%). Combined alpha-, beta-, and cholinergic blockades abolished the systemic hemodynamic and coronary vasoconstrictor response to cocaine.
CONCLUSIONS
In conscious dogs, cocaine induces coronary vasoconstriction, which competes with coronary vasodilator responses to increases in myocardial oxygen consumption. The mechanisms of cocaine's coronary vascular effects are mediated via adrenergic stimulation, and the intensity of the vasoconstrictor effects was reduced significantly by cholinergic blockade, in both the presence and absence of beta-adrenergic receptor blockade.
Topics: Animals; Cocaine; Coronary Circulation; Dogs; Dose-Response Relationship, Drug; Female; Hemodynamics; Male; Norepinephrine; Parasympathetic Nervous System; Vasoconstriction
PubMed: 8443913
DOI: 10.1161/01.cir.87.3.939 -
Neuropharmacology Mar 2005We investigated the effects of agmatine, clonidine, xylazine and moxonidine on the purinergic vasoconstriction induced by electrical stimulation in the rabbit isolated... (Comparative Study)
Comparative Study
We investigated the effects of agmatine, clonidine, xylazine and moxonidine on the purinergic vasoconstriction induced by electrical stimulation in the rabbit isolated saphenous artery without endothelium. Transmural electrical stimulations induced reproducible responses in the arterial preparations, which were abolished by tetrodotoxin at 0.1 microM or pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium salt (PPADS, 30 microM), but were not affected by 1 microM prazosin. Clonidine, xylazine and moxonidine induced transient and concentration-independent vasoconstriction, with threshold concentrations of 1, 3 and 30 microM, respectively. Agmatine, in contrast, did not produce any vascular response even at 1 mM. Lower concentrations of clonidine, xylazine and moxonidine (0.01-0.3 microM) concentration-dependently decreased vasoconstrictor responses to electrical stimulation, whereas agmatine (0.1-1 mM) induced an inhibitory followed by a facilitatory effect on electrically evoked responses. Agmatine, clonidine and moxonidine but not xylazine significantly enhanced the vasoconstriction elicited by 1 mM ATP. The concentration-response curve for NA was shifted to the left slightly by 1 mM agmatine, but not affected by 0.3 microM of other three agonists. Phenoxybenzamine did not affect the vasoconstrictive responses to 1mM ATP and to electrical stimulations, but abolished those to NA. Agmatine at 1mM evoked only an inhibitory effect on electrical stimulation-induced vasoconstriction in the preparation pretreated with phenoxybenzamine, and the inhibitory action was enhanced to 38.6% from the control value (without treatment with phenoxybenzamine) of 22.5%. The non-imidazoline compound xylazine at 0.3 microM lost its inhibitory effect on the neurogenic vasoconstriction in the presence of phenoxybenzamine. In conclusion, agmatine produces a biphasic effect on the purinergic vasoconstriction induced by sympathetic nerve stimulation in the rabbit isolated saphenous artery. The monophasic inhibition of agmatine in the artery treated with phenoxybenzamine is due to an alpha-adrenoceptor-independent mechanism at prejunctional sites, and the potentiation effect of agmatine is mainly dependent on its enhancement of vasoconstriction at postjunctional sites.
Topics: Agmatine; Animals; Arteries; Dose-Response Relationship, Drug; Electric Stimulation; In Vitro Techniques; Lower Extremity; Male; Neural Inhibition; Norepinephrine; Presynaptic Terminals; Rabbits; Receptors, Adrenergic, alpha; Receptors, Purinergic; Vasoconstriction
PubMed: 15755487
DOI: 10.1016/j.neuropharm.2004.12.004 -
Biomedical Papers of the Medical... Dec 2007Humoral systems play an important role in the pathophysiology and development of chronic heart failure (CHF). (Review)
Review
BACKGROUND
Humoral systems play an important role in the pathophysiology and development of chronic heart failure (CHF).
METHODS
We conducted a search of neurohumoral activation in heart failure and its risk in the development of CHF.
RESULTS AND CONCLUSION
Neurohumoral factors may be divided into vasoconstrictive, vasodilative and cytokines. The main vasoconstrictive systems are the renin-angiotensin-aldosterone system (RAAS) and the sympathoadrenal system (SAS). Cytokines include tumour necrosis factor (TNF) alpha and interleukins. The systems of actions are interconnected and they mutually influence their secretion and activities. The possibilities of their detection and assessment for clinical purposes depend on their changes and kinetics in the organism and on the activity of individual metabolites. Apart from their vasoactive effects, the majority of humoral actions also interfere in the process of remodelling, function of the endothelium, blood elements, cardiomyocytes, cells of the smooth muscles, and in immunity as well as inflammatory processes. The rapid development of knowledge on the humoral actions in recent years has made possible their utilisation in diagnostics, treatment and prognosis.
Topics: Cytokines; Heart Failure; Humans; Neurosecretory Systems; Vasoconstriction; Vasodilation
PubMed: 18345252
DOI: 10.5507/bp.2007.035 -
British Journal of Pharmacology Mar 20051. The contribution of postjunctional P2X receptors and subtypes of alpha-adrenoceptors to vasoconstrictor responses following periarterial electrical nerve stimulation... (Comparative Study)
Comparative Study
1. The contribution of postjunctional P2X receptors and subtypes of alpha-adrenoceptors to vasoconstrictor responses following periarterial electrical nerve stimulation (PNS, 30 s trains of pulses at a frequency of 2, 4 or 8 Hz) was investigated in human gastroepiploic arteries. 2. The vasoconstrictor response to PNS at a stimulation of 4 or 8 Hz was a two-peaked response, whereas at a frequency of 2 Hz it appeared only as a late peak. All vasoconstrictions evoked by PNS were abolished by phentolamine, a nonselective alpha-adrenoceptor inhibitor, but not by alpha,beta-methylene ATP, a P2X receptor-desensitizing agent. 3. The early peak to PNS at 4 or 8 Hz was abolished by prazosin, an alpha1-adrenoceptor antagonist, while the late one still remained, although it was markedly inhibited. The responses remaining after prazosin were blocked by rauwolscine. The vasoconstrictor response to PNS at 2 Hz was not affected by prazosin (0.1 microM), but was abolished by rauwolscine (0.1 microM), an alpha2-adrenoceptor antagonist. 4. OPC-28326 (10 microM), a newly developed vasodilator, which preferentially exerts its antagonistic actions on the alpha2B- and alpha2C-adrenoceptors, significantly reduced the noradrenaline-induced vasoconstriction in the absence or presence of prazosin. OPC-28326 had a greater inhibitory effect on the late peak evoked by PNS than the early one. The neurogenic responses remaining after OPC-28326 were abolished by prazosin. 5. The present results suggest that sympathetic vasoconstriction of the human gastroepiploic artery is mediated by both alpha1- and alpha2-adrenoceptors postjunctionally, but not by P2X receptors. The alpha2-adrenoceptors may be preferentially activated at a low frequency of stimulation, which induces a constriction more slowly than that by alpha1-adrenoceptors. The existence of alpha2-adrenoceptors may cause an enhancement of alpha1-adrenoceptor-induced responses.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Aged; Aniline Compounds; Dose-Response Relationship, Drug; Drug Interactions; Electric Stimulation; Female; Gastroepiploic Artery; Humans; Male; Middle Aged; Norepinephrine; Perfusion; Piperidines; Prazosin; Receptors, Adrenergic, alpha; Time Factors; Vasoconstriction; Vasoconstrictor Agents; Vasodilator Agents; Yohimbine
PubMed: 15685216
DOI: 10.1038/sj.bjp.0705975 -
European Journal of Pharmacology Jan 2003The aim of this study was to determine the role of nuclear factor-kappaB (NF-kappaB) in hypoxic constriction of isolated pulmonary arteries. Rings were suspended in an...
The aim of this study was to determine the role of nuclear factor-kappaB (NF-kappaB) in hypoxic constriction of isolated pulmonary arteries. Rings were suspended in an organ bath filled with Krebs-Henseleit solution and isometric contractions were recorded continuously. Hypoxia (%95 N(2)-%5 CO(2)) had no marked effect on resting force in artery rings. However, hypoxia caused further contractions in serotonin-precontracted arteries. Hypoxia-induced vasoconstrictions were abolished by preincubation with NF-kappaB inhibitors, pyrrolidine dithiocarbamate (100 microM) or pyrithione (10 microM). These results suggest that reactive oxygen species and/or NF-kappaB activation may be involved in the hypoxia-induced vasoconstriction in sheep-isolated pulmonary arteries.
Topics: Animals; Hypoxia; In Vitro Techniques; NF-kappa B; Pulmonary Artery; Pyridines; Pyrrolidines; Serotonin; Sheep; Thiocarbamates; Thiones; Vasoconstriction
PubMed: 12498922
DOI: 10.1016/s0014-2999(02)02761-9 -
British Journal of Pharmacology Feb 19931. The role of endothelin-1 in mediating the phenomenon of hypoxic vasoconstriction was examined in canine, isolated pulmonary, circumflex coronary and femoral arterial...
1. The role of endothelin-1 in mediating the phenomenon of hypoxic vasoconstriction was examined in canine, isolated pulmonary, circumflex coronary and femoral arterial rings. 2. In tissues with an intact endothelium, the exogenous application of endothelin-1 (0.1-300 nM) caused concentration-dependent increases in canine, isolated pulmonary artery tone. Endothelin-3 (1-300 nM) was approximately 30 fold less potent than endothelin-1 as a vasoconstrictor in this tissue. In contrast, the selective ETB-receptor agonist, sarafotoxin S6c (0.01-1 microM), failed to elicit vasoconstriction in this tissue. Thus, endothelin isopeptide-induced vasoconstriction of the canine isolated pulmonary artery is mediated exclusively by the ETA-receptor subtype. 3. The concentration-dependent increases in isometric tension induced by endothelin-1 (0.1-300 nM) were antagonized by the ETA-selective antagonist, BQ-123 (10 microM); this concentration of antagonist caused a shift to the right in the concentration-response curve for endothelin-1 of approximately two orders of magnitude. This concentration of BQ-123 did not unmask any ETB-receptor-mediated vasoconstriction since sarafotoxin S6c (0.01-1 microM) still failed to elicit contraction in the presence of this concentration of BQ-123. 4. The hypoxia-induced vasoconstriction of canine, isolated pulmonary, circumflex coronary and femoral arterial rings was unaffected by pretreatment with the endothelin receptor antagonist, BQ-123 (10 microM), a concentration shown previously to antagonize the contractile actions of exogenously applied endothelin-1 in the isolated pulmonary artery. 5. These results are the first to provide direct evidence showing that the endothelium-dependent vasoconstriction observed during acute periods of hypoxia in vitro is not mediated by an endothelin-related isopeptide.
Topics: Amino Acid Sequence; Animals; Blood Vessels; Dogs; Endothelins; Hypoxia; In Vitro Techniques; Male; Molecular Sequence Data; Peptides, Cyclic; Vasoconstriction
PubMed: 8448593
DOI: 10.1111/j.1476-5381.1993.tb12819.x -
Circulation Aug 1994Physical activity can reduce sympathetic tone and may be beneficial to human health. Whether the vascular responses to norepinephrine (NE), an adrenergic... (Comparative Study)
Comparative Study
BACKGROUND
Physical activity can reduce sympathetic tone and may be beneficial to human health. Whether the vascular responses to norepinephrine (NE), an adrenergic vasoconstrictor, could be altered by chronic exercise was unclear. We therefore conducted this study to investigate the effects of endurance exercise training on NE-induced vasoconstrictive response in healthy rabbits. Possible mechanisms were also studied.
METHODS AND RESULTS
Twenty-four male New Zealand White rabbits were used for this study. They were divided into two groups: control and training. The training group was trained on a treadmill with running speed of 0.88 km/h at a 0 degree grade for 10 to 60 minutes per day, for 5 days a week for a total of 8 weeks. At the end of the experiments, thoracic aortae (3 mm long) were isolated. The vascular tension was measured with a force transducer. The dose-response relation of NE-induced vasoconstriction was determined and compared for control (n = 5) and trained (n = 6) groups. To verify the possible involvement of endothelium-derived relaxing factor (EDRF) in the alteration of NE-induced vasoconstriction after exercise training, we compared the vascular responses to NE in endothelium-intact, N omega-nitro-L-arginine (L-NNA, 10(-4) mol/L)-pretreated, or denuded vessel segments (n = 4 for each experiment of each group). EDRF release in the presence or absence of NE was also evaluated by the increased tension induced by hemoglobin (10(-5) mol/L), an EDRF scavenger (n = 6 for the control group and n = 8 for the trained group). In addition, vascular responses to some specific adrenergic agonists (ie, phenylephrine, an alpha 1-agonist, and clonidine, an alpha 2-agonist) were also studied to see if a specific adrenergic receptor was involved (n = 4 for each experiment of each group). Our results indicated that (1) [NE]ED50 of the thoracic aorta was elevated by exercise training; (2) in the presence of NE, EDRF release from the thoracic aorta, assessed by addition of hemoglobin or L-NNA, was higher in the trained group than in the control group; (3) both phenylephrine (10(-8) mol/L) and clonidine (10(-6) mol/L) could evoke vasorelaxation that would be inhibited by L-NNA; and (4) in addition to causing vasoconstriction, NE could stimulate EDRF release, possibly via alpha 1- and alpha 2-receptors of endothelial cells.
CONCLUSIONS
Our data suggest that exercise training may decrease NE-induced vasoconstrictive response and may increase NE-stimulated EDRF release.
Topics: Animals; Aorta, Thoracic; Clonidine; Dose-Response Relationship, Drug; Endothelium, Vascular; Male; Nitric Oxide; Norepinephrine; Phenylephrine; Physical Conditioning, Animal; Rabbits; Receptors, Adrenergic, alpha; Vasoconstriction
PubMed: 8044969
DOI: 10.1161/01.cir.90.2.970 -
Pharmacological Research Dec 2004Haloperidol is a widely used antipsychotic drug, which exerts its effects via antagonizing the dopaminergic D2 receptors. Also it affects a number of receptors on... (Comparative Study)
Comparative Study
Haloperidol is a widely used antipsychotic drug, which exerts its effects via antagonizing the dopaminergic D2 receptors. Also it affects a number of receptors on vascular bed and other tissues. The impact of haloperidol on vascular bed seems still debatable and not clear. In the present study, haloperidol was given to adult rats in 0.5, 1, 2.5 and 5 mg kg(-1) doses, once a day, intraperitoneally in 1 ml volumes, for 9 weeks. After decapitation under Pentothal anesthesia, brains and basilar arteries were dissected out at midpontine level immediately. Conventional histopathology and morphometric analysis were carried out on the dissected artery branches. Medial and adventitial layers, endothelial cells and internal elastic membranes were observed as normal in the control group. It was determined clearly that the lumen of basilar artery in the control group was larger than in the other groups and also it was observed that is more regular the lumen contours of basilar artery in control group compared with other groups. Finally, wall thickness of basilar artery in all experimental groups decreased significantly due to the vasoconstriction. Regarding the total, lumen and wall volumes, 1 mg kg(-1) haloperidol induces vasoconstriction more than the other groups.
Topics: Animals; Basilar Artery; Dose-Response Relationship, Drug; Haloperidol; Male; Rats; Rats, Wistar; Vasoconstriction
PubMed: 15501694
DOI: 10.1016/j.phrs.2004.06.003