Isolated Dog Cerebral Arteries Research Articles

Volatile anaesthetics attenuate hypocapnia-induced constriction in isolated dog cerebral arteries

Hypocapnia causes cerebral arterial constriction, whereas volatile anaesthetics cause dilatation. The purpose of this study was to compare the direct effects of halothane, isoflurane and sevoflurane on hypocapnia-induced constriction of isolated cerebral arteries in vitro. Basilar and middle cerebral arteries of mongrel dogs (n = 11) were cut into rings and mounted for isometric tension recording in organ baths containing Krebs' bicarbonate solution, aerated with CO2 5% and O2 95% at 37 degrees C. After constriction with 20 mM KCl, hypocapnia was induced by replacing the aerating gas with CO2 2.5% and O2 97.5% in the presence or absence of anaesthetics. Exposure of cerebroarterial rings to the hypocapnic gas produced sustained vasoconstriction (418 +/- 19 mg), reaching a plateau within 10 to 15 min. Halothane (0.5, 1, 2 MAC) attenuated the hypocapnia-induced constriction (P < 0.05). In contrast, isoflurane and sevoflurane attenuated this constriction only at 2 MAC (P < 0.05). Attenuation by halothane was greater than that by isoflurane or sevoflurane at each concentration (P < 0.05). NG-nitro-L-arginine (3 x 10(-5) M) did not alter the contractile response to hypocapnia. When a similar degree of constriction was induced by addition of 10 mM KCl, halothane (1 and 2 MAC) preferentially attenuated the constriction induced by hypocapnia to a greater extent than that induced by 10 mM KCl (P < 0.01). Hypocapnia-induced vasoconstriction of isolated dog cerebral arteries precontracted with KCl is more susceptible to halothane than isoflurane or sevoflurane. This may account for the greater increase in cerebral blood flow during halothane than isoflurane or sevoflurane anaesthesia.

O-016 - Suppression by L-NG-monomethyl arginine of the response to vasodilator nerve stimulation in isolated dog cerebral arteries

O-016 - Suppression by L-NG-monomethyl arginine of the response to vasodilator nerve stimulation in isolated dog cerebral arteries

Mechanisms underlying response to hypercapnia and bicarbonate of isolated dog cerebral arteries

In helical strips of dog cerebral arteries contracted with K+ or prostaglandin F2 alpha, the increase in CO2 from 5 to 15% in the gas aerating the bathing media produced a persistent relaxation in association with a rise of PCO2 and a fall of pH and PO2. Elevation of the NaHCO3 concentration from 25 to 75 mM in the bathing media under hypercapnia almost reversed the arterial tone when the osmolarity was balanced; the pH was completely reversed, whereas PCO2 was maintained at the high level. When 50 mM NaHCO3 were applied to the hypercapnic media without having the osmolarity balanced, the arteries relaxed further. Infusions of the HCl solution lowered the pH and relaxed the arterial strips; however, such a relaxation was significantly less than that caused by hypercapnia-induced acidosis. Relaxant responses to hypercapnia were attenuated by treatment with ouabain but were not influenced by amiloride and superoxide dismutase or by removal of endothelium. Relaxations due to hypertonic NaHCO3 were abolished or reversed to contractions by ouabain and were reduced by treatment with amiloride. It may be concluded that the hypercapnia-induced cerebroarterial relaxation is associated mainly with a fall of extracellular pH and is mediated partly by an activation of the electrogenic Na+ pump. Cerebral vasodilatation by increased osmolarity with NaHCO3 appears to result from stimulated Na+-H+ exchange and activated Na+ pump.

O-069 - Modification by vasodilator agents of reoxygention- and calcium- induced contractions in isolated dog cerebral arteries.

O-069 - Modification by vasodilator agents of reoxygention- and calcium- induced contractions in isolated dog cerebral arteries.

Endothelium-dependent and -independent responses to vasodilators of isolated dog cerebral arteries.

We compared responses to calcium ionophore A23187, vasopressin, and substance P in helical strips of dog middle cerebral, basilar, and posterior communicating arteries to obtain a better understanding of humoral control of cerebrovascular tone in different brain regions and its potential impact on mechanisms of cerebral vasospasm. A23187 relaxed these different arterial strips partially precontracted with prostaglandin F2 alpha to a similar extent. Vasopressin produced concentration-dependent relaxation in basilar and posterior communicating arterial strips, whereas middle cerebral arterial strips either contracted or relaxed slightly. Relaxations induced by A23187 and vasopressin were either abolished or converted to contractions by removal of the endothelium. In contrast, the relaxation of cerebral arterial strips to substance P was markedly attenuated but not abolished by endothelium denudation; the remaining relaxation was suppressed by indomethacin. In some cerebral arterial strips with intact endothelium, substance P caused a transient contraction that was reversed to a relaxation by indomethacin or ONO-3708, a prostaglandin antagonist. In arterial strips denuded of endothelium from the same dogs, substance P always produced relaxations. Relaxations of cerebral arterial strips to A23187 and vasopressin appear to be mediated by endothelium-derived relaxing factor. The function of vasopressin receptors in endothelial cells differs markedly in basilar and posterior communicating arteries versus middle cerebral arteries. Substance P-induced relaxations appear to be primarily associated with endothelium-derived relaxing factor and with prostaglandin I2, whereas contractions appear to be mediated by endothelium-derived prostaglandins.

Characterization of muscarinic cholinergic receptors in human and dog cerebral arteries.

Various concentrations of acetylcholine (ACh) produced dose dependent relaxations of isolated, helical preparations of human cerebral arteries and these responses were blocked by atropine. The median effective concentration (EC50) of ACh was 6.1 +/- 0.2 X 10(-6)M. ACh produced dual responses in isolated dog cerebral arteries. ACh in low concentrations produced relaxation, and contraction occurred when the concentration was raised to 1 X 10(-5)M. The EC50 of ACh which produced relaxation, in dog cerebral arteries was 7.2 +/- 0.2 X 10(-7)M. Muscarinic cholinergic receptors in these arteries were analyzed directly using 3H-QNB as the ligand. The specific 3H-QNB binding to the arteries was saturable and of KD = 1.5 nM and Bmax = 93 fmol/mg protein in human cerebral arteries and KD = 0.59 nM, Bmax = 340 fmol/mg protein in dog cerebral arteries. Specific binding of 3H-QNB was displaced by muscarinic cholinergic agents. Ki values and Hill coefficients were as follows: QNB, 1.0 X 10(-9)M, 0.89; atropine, 1.1 X 10(-8)M, 0.95; ACh, 0.8 X 10(-8)M and 2.1 X 10(-6)M, 0.54; carbachol, 1.2 X 10(-7)M and 4.3 X 10(-5)M, 0.33 in human cerebral arteries and QNB, 0.55 X 10(-9)M, 0.85; atropine 0.9 X 10(-9)M, 1.00; ACh, 0.9 X 10(-9)M and 1.1 X 10(-6)M, 0.43; carbachol 6.3 X 10(-8)M and 1.1 X 10(-5)M, 0.36 in dog cerebral arteries. Endogenous choline acetyltransferase (ChAT) activity was 1.6 +/- 0.4 nmol/mg protein/hr in human cerebral arteries and 3.7 +/- 0.1 nmol/mg protein/hr in dog cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cinepazide on the purinergic responses in the dog cerebral artery.

The effects of cinepazide, 1-[(1-pyrrolidinylcarbonyl)methyl]-4-(3,4,5-trimethoxycinnamoyl )piperazine hydrogen maleate, were studied in isolated dog cerebral arteries. Cinepazide in concentrations ranging from 10(-6) to 10(-5) M augmented the relaxing responses to ATP, adenosine and cAMP. However, this agent did not affect the relaxations induced by isoproterenol and papaverine and the contractions induced by 5-HT, prostaglandin F2 alpha and ATP. In the basilar artery preloaded with 3H-norepinephrine or 3H-adenosine, electrical transmural stimulation resulted in a marked increase in 3H-efflux. This efflux accompanied an initial transient contraction followed by a relaxation. Cinepazide slightly reduced the 3H-efflux evoked by electrical stimulation. However, the relaxing response was mostly augmented by the treatment with cinepazide. The relaxing responses to ATP, adenosine, cAMP and electrical transmural stimulation were attenuated by theophylline. These results suggest that cinepazide selectively potentiates the relaxing response mediated through purinergic P1-receptors.

Evidence for greater susceptibility of isolated dog cerebral arteries to Ca antagonists than peripheral arteries.

In helically-cut strips of dog cerebral, coronary and mesenteric arteries, contracted with prostaglandin (PG) F2 alpha or K+, the addition of verapamil caused a dose-related relaxation. Verapamil-induced relaxations were greater in cerebral than in the other arteries when contracted with PGF2 alpha, but did not significantly differ in the arteries contracted with K+. Similar results were obtained with diltiazem and nifedipine. The contractile response to PGF2 alpha was attenuated by pretreatment with verapamil, the ateenuation being greater in cerebral than in mesenteric arteries. Nitroglycerin and sodium nitroprusside relaxed cerebral, coronary and mesenteric arteries contracted with PGF2 alpha to a similar extent. It may be concluded that dog cerebral arteries contracted with PGF2 alpha, one of endogenous vasospastic substances, are more susceptible to agents which interfere with the influx of Ca++ across cell membranes than coronary and mesenteric arteries; these agents may thus be of value in the treatment and prophylaxis of cerebral vasopasm.

Structure-Activity Relationship of 5-Hydroxykynurenamine Analogues in Isolated Dog Cerebral Arteries

In helically-cut strips of cerebral arteries isolated from dogs, analogues of 5-hydroxykynurenamine (5-HK), including 2-(3’-aminopropyl)-aniline (Cpd. I), 2’-amino-3-dimethylamino-3’-hydroxypropiophenone(Cpd. II), 2’-amino-3-dimethylamino-5’-hydroxypropiophenone (Cpd. III) and 2’,3-diamino-propiophenone (kynurenamine), caused a dose-related contraction which was antagonized by treatment with methysergide. The potency for inducing contractions was in the order of 5-hydroxy-tryptamine>5-HK>Cpd. III>kynurenamine, Cpd. I and Cpd. II. Treatment with the 5-HK analogues antagonized the contractile response to 5-hydroxytryptamine in a dose-dependent manner, the antagonistic potency being in the order of 5-HK>Cpd. III>kynurenamine, Cpd. II>Cpd. I. Alterations in the hydroxy group on the benzene ring and/or radicals of long side chain of 5-HK attenuated the agonistic and antagonistic actions of 5-HK; however, the attenuation of these actions differed. Thus, the radicals appear to be involved in the agonistic and antagonistic actions to a different extent.

Structure-activity relationship of 5-hydroxykynurenamine analogues in isolated dog cerebral arteries.

In helically-cut strips of cerebral arteries isolated from dogs, analogues of 5-hydroxykynurenamine (5-HK), including 2-(3'-aminopropyl)-aniline (Cpd. I), 2'-amino-3-dimethylamino-3'-hydroxypropiophenone(CPD. II), 2'-amino-3-dimethylamino-5'-hydroxypropiophenone (Cpd. III) and 2',3-diamino-propiophenone (kynurenamine), caused a dose-related contraction which was antagonized by treatment with methysergide. The potency for inducing contractions was in the order of 5-hydroxytryptamine greater than 5-HK greater than Cpd. III greater than kynurenamine, Cpd. I and Cpd. II. Treatment with the 5-HK analogues antagonized the contractile response to 5-hydroxytryptamine in a dose-dependent manner, the antagonistic potency being in the order of 5-HK greater than Cpd. III greater than kynurenamine, Cpd. II greater than Cpd. I. Alterations in the hydroxy group on the benzene ring and/or radicals of long side chain of 5-HK attenuated the agonistic and antagonistic actions of 5-HK; however, the attenuation of these actions differed. Thus, the radicals appear to be involved in the agonistic and antagonistic actions to a different extent.

Vasoconstrictor and dilator actions of nicotine and electrical transmural stimulation on isolated dog cerebral arteries.

Effects of nicotine and electrical transmural stimulation on isolated dog cerebral arteries were studied. Nicotine (5 × 10&lt;sup&gt;–8&lt;/sup&gt;–10&lt;sup&gt;–4&lt;/sup&gt; m) usually evoked a phasic contraction in the basilar artery and a relaxation in the middle cerebral artery. The nicotine-induced contraction and relaxation were abolished by pretreatment with pentolinium (10&lt;sup&gt;–5&lt;/sup&gt; m) but not by tetrodotoxin (TTX) (10&lt;sup&gt;–7&lt;/sup&gt; m). Phentolamine (10&lt;sup&gt;–6&lt;/sup&gt; m) or bretylium (10&lt;sup&gt;–5&lt;/sup&gt; m) abolished or reversed the nicotine-induced contraction, and partially reduced the nicotine-induced relaxation. Electrical transmural stimulation elicited a phasic contraction in the basilar artery and a relaxation or slight contraction in the middle cerebral artery. The contraction induced by transmural stimulation was abolished by bretylium and TTX, and augmented by phentolmine. The relaxation was not inhibited by bretylium. The uptake of &lt;sup&gt;3&lt;/sup&gt;H-norepinephrine (&lt;sup&gt;3&lt;/sup&gt;H-NE) by the basilar and middle cerebral arteries was markedly reduced by cocaine (3 × 10&lt;sup&gt;–6&lt;/sup&gt; m). Nicotine and transmural stimulation increased the tritium efflux from both arteries. The nicotine-induced increase in tritium efflux was inhibited by pentolinium. The increased efflux induced by transmural stimulation was abolished by TTX, attenuated by bretylium, and augmented by phentolamine. These results indicate that nicotine and transmural stimulation cause both vasoconstrictor and vasodilator effects in the dog cerebral arteries and that the vasoconstriction is mediated through an adrenergic mechanism.

142) - Effects of acetylcholine on isolated dog cerebral arteries

142) - Effects of acetylcholine on isolated dog cerebral arteries

Influence of cadmium ions on contractile response of isolated aortas to stimulatory agents.

Influence of cadmium ions on contractile response of isolated aortas to stimulatory agents.