Dopamine vasodilates human cerebral artery.
In human large pial arteries, dopamine-induced relaxations appear to be mediated via dopaminergic receptors, and predominate over contractions mediated via alpha-adrenoceptors.
Adolescent↗
Biomedical subjects
N Toda
Publications and source records attributed to N Toda.
Heterogeneity in the response to dopamine of monkey cerebral and peripheral arteries.
In helical strips of monkey cerebral and mesenteric arteries contracted with prostaglandin F2 alpha, dopamine in low concentrations produced a moderate relaxation but in high concentrations produced a contraction from the level of relaxation. On the other hand, coronary, renal, and femoral arterial strips responded to dopamine with only a concentration-dependent contraction. Treatment with phenoxybenzamine or phentolamine potentiated the dopamine-induced relaxation seen in cerebral and mesenteric arteries and reversed the contraction in the other arteries to a relaxation. After treatment with phenoxybenzamine, relaxant responses to dopamine of cerebral, mesenteric, and renal arteries were almost identical, and, compared with those, the responses of coronary and femoral arteries were appreciably less. Relaxations induced by dopamine were not influenced by propranolol, atropine, aminophylline, cimetidine, and aspirin but were markedly attenuated by droperidol. Adenosine-induced relaxations were not affected by droperidol. It is concluded that dopamine preferentially relaxes monkey cerebral and mesenteric arteries, possibly via dopaminergic receptors. It appears that the dopamine-induced contractions mediated by alpha-adrenoceptors predominate over the relaxation in coronary, renal, and femoral arteries, and dopaminergic receptor function is greater in cerebral, mesenteric, and renal arteries than in coronary and femoral arteries.
Adenosine↗
Isolated human coronary arteries in response to vasoconstrictor substances.
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.
Acetylcholine↗
Modification of angiotensin II-induced relaxation by dipyridamole, phthalazinol and aspirin in isolated dog renal arteries.
Angiotensin (ANG) II-induced relaxations in isolated dog renal and cerebral arteries are postulated to be mediated by the release of prostaglandin (PG) I2 from the arterial wall. In helical strips of dog renal arteries treated with dipyridamole, relaxations induced by ANG II (10(-7) M) and exogenously applied PGI2 (10(-8) M) were potentiated; the potentiation was appreciably greater in the ANG-induced relaxation. Treatment with phthalazinol did not alter the response to ANG II, but significantly potentiated the relaxation induced by PGI2. The ANG-induced relaxations were suppressed or reversed to contractions by aspirin or indomethacin. Combined treatment of dipyridamole with aspirin or indomethacin restored the relaxant response to ANG II, while phthalazinol in combination with aspirin did not restore the response. It may be concluded that the potentiation of responses to ANG II by dipyridamole is associated with increments in the release of PGI2 from the arterial wall and potentiations of the response of arterial smooth muscle to PGI2. Dipyridamole appears to increase the production of PGI2 even in the presence of PG synthesis inhibition by aspirin or indomethacin.
3',5'-Cyclic-AMP Phosphodiesterases↗
Analysis of the contractile response to serotonin and tryptamine of isolated dog cerebral, femoral and mesenteric arteries.
In helically-cut strips of cerebral arteries isolated from dogs, serotonin, tryptamine, 5-hydroxytryptophan and tryptophan caused a dose-related contraction. The potency was in the order of serotonin greater than tryptamine much greater than 5-hydroxytryptophan = tryptophan. In femoral arterial strips, only serotonin and tryptamine produced contractions. In cerebral arteries, the dose-response curve for serotonin was shifted to the right and downward by treatment with cinanserin, whereas in femoral and mesenteric arteries, the curves were shifted to the right. The contractile response of cerebral arteries to tryptamine was attenuated by cinanserin in concentrations above 10(-7) M; however, 10(-5) M was required to significantly reduce the response of femoral arteries. Phentolamine reduced the contractile response of femoral arteries to tryptamine, but not the response of cerebral arteries. It may be concluded that the different antagonism of cinanserin against the serotonin action on cerebral and femoral arteries is due to the ability of high concentrations of serotonin to induce relaxations of cerebral but not femoral arteries or to the different nature of receptors. Tryptamine appears to elicit contractions of cerebral arteries via a stimulation of tryptamine receptors, but elicit those of femoral arteries via stimulation of both alpha-adrenergic and tryptamine receptors. Whether or not receptors for serotonin and tryptamine are the same was not determined.
5-Hydroxytryptophan↗
Modification by cadmium ions of 45calcium uptake by isolated rabbit aortae.
Treatment with 0.5 mM Cd++ suppressed the K+ (30 mM)-stimulated uptake and influx of 45Ca and abolished the K+-induced contraction in helical strips of rabbit aortae. The rapid and slow efflux of 45Ca previously accumulated was not appreciably affected by Cd++. It is concluded that interference with the transmembrane influx of Ca++ is a major mechanism of Cd++ action.
Animals↗
The effects of ethanol and acetaldehyde on dog arterial smooth muscle.
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Acetaldehyde↗
Alpha adrenergic receptor subtypes in human, monkey and dog cerebral arteries.
In helical strips of human and monkey cerebral arteries, norepinephrine produced a greater contraction than that in dog cerebral arteries. In monkey cerebral arteries, phenylephrine and norepinephrine produced a similar magnitude of maximum contractions, although the ED50 value of phenylephrine was approximately 5.6 times greater than that of norepinephrine. Clonidine (up to 10(-5) M) did not produce contractions. Dog cerebral arteries responded to phenylephrine in high concentrations with a greater contraction than that induced by norepinephrine and to clonidine with significant contractions. Contractions induced by norepinephrine of human and monkey cerebral arteries were attenuated by low concentrations of prazosin but were not influenced by yohimbine in concentrations up to 10(-8) M. In contrast, norepinephrine-induced contractions of dog cerebral arteries were attenuated by yohimbine but were unaffected by prazosin. It appears that norepinephrine-induced contractions are mediated by alpha-2 adrenoceptors in dog cerebral arteries and by alpha-1 receptors in human and monkey cerebral arteries as well as monkey and dog mesenteric arteries. The relative unresponsiveness of monkey and dog cerebral arteries to adrenergic nerve stimulation may not be explained by a paucity of alpha adrenoceptors in neuroeffector junction.
Adolescent↗
[Response of vascular smooth muscle to various drugs].
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Angiotensin II↗
Effects of buflomedil on isolated dog arteries.
Buflomedil (10(-6) to 10(-4) M) relaxed, in a concentration-dependent manner, helical strips of dog mesenteric, renal and femoral arteries, partially contracted due to previous exposure to noradrenaline. When partial contraction was caused by prostaglandin F2 alpha, Buflomedil produced a slight relaxation of the mesenteric and coronary arterial strips, had no effect in cerebral and femoral arteries and caused a small contraction of renal arterial strips. Buflomedil did not reduce contractions induced by submaximal concentrations of K+ in normal media and those induced by Ca++ in mesenteric arteries exposed to Ca++-free media and depolarized by excess K+. Contractile responses to transmural electrical stimulation and exogenous noradrenaline were attenuated by buflomedil; the attenuations in femoral and mesenteric arteries did not differ. Protection against persistent blockade of alpha-adrenoceptors by phenoxybenzamine was obtained by pretreatment of mesenteric arteries with buflomedil. Relaxant responses of cerebral and coronary arteries to nicotine were suppressed or abolished by buflomedil, whereas the relaxation of coronary arteries induced by tyramine was unaffected or reduced only slightly. It is concluded that buflomedil reversibly blocks alpha-adrenoceptors in arterial smooth muscle and possesses an anti-nicotinic action. As far as the concentrations used in the present study are concerned, buflomedil does not appear to interfere with the transmembrane influx of Ca++.
Animals↗
[Antihypertensive action of elcatonin].
Subcutaneous injections of elcatonin, a synthetic analogue of eel calcitonin, lowered the blood pressure in DOCA/saline-hypertensive and spontaneously hypertensive rats (SHR), but not in normotensive Wistar rats. The hypotensive effect was more prominent in the DOCA hypertensive rats. Daily injections of elcatonin (10-30 U/kg/day for 21 days) resulted in maximum hypotension on the 4th day in DOCA hypertensive rats and on the 14th day in SHR, and the reduced level of blood pressure was maintained. After the cessation of elcatonin injections, the pressure started to elevate gradually towards the control level. In normotensive rats, elcatonin did not significantly alter the blood pressure for 6 weeks. Daily injections of elcatonin significantly prevented the development of DOCA-induced hypertension and spontaneously-occurring hypertension. Elcatonin-induced hypotension did not differ in the control and parathyroidectomized DOCA hypertensive rats. Elcatonin did not alter the pressor response to noradrenaline, vasopressin and angiotensin II nor the depressor response to isoproterenol, acetylcholine and histamine in DOCA hypertensive rats. It is concluded that the antihypertensive effect of elcatonin is not associated with the release of parathyroid hormone nor with the blockade of alpha, beta, angiotensin II and vasopressin receptors.
Animals↗
Direct effects of ketamine on isolated canine cerebral and mesenteric arteries.
The effects of ketamine on isolated canine cerebral (middle cerebral and basilar) and mesenteric arteries were studied. In arteries contracted with KCl, ketamine in concentrations above 5 X 10(-6)M (cerebral arteries) or 2 X 10(-5)M (mesenteric arteries) caused significant relaxation in a dose-dependent manner. The relaxation was not significantly influenced by aminophylline, aspirin, atropine, or propranolol. In concentrations above 5 X 10(-6)M ketamine attenuated the contractile response to high concentrations of KCl in the middle cerebral arteries, and in concentrations above 5 X 10(-5)M it attenuated the contractile response to high concentrations of KCl in the basilar and mesenteric arteries. The attenuation was greater in cerebral than in mesenteric arteries. The contractile response of cerebral arteries to high concentrations of serotonin was also attenuated by ketamine in concentrations above 5 X 10(-5)M. Ketamine attenuated KCl-induced contraction of cerebral arteries more than it attenuated serotonin-induced contraction. When basilar arteries were exposed to Ca2+-free media and depolarized by KCl, the addition of Ca2+ caused biphasic (transient and sustained) contractions, while in the mesenteric arteries the addition of Ca2+ produced sustained contractions. Ketamine at 5 X 10(-5) and 5 X 10(-4)M attenuated both transient and sustained contractions in basilar arteries, while in mesenteric arteries 5 X 10(-4)M ketamine attenuated only sustained contractions. In both instances, ketamine-induced attenuation was partially reversed by excess Ca2+. It is concluded that ketamine has a direct dilating effect on both cerebral and mesenteric arteries, but the effect is more pronounced in cerebral than in mesenteric arteries. The direct action of ketamine on those arteries may be due in part to interference with transmembrane influx of Ca2+.
Animals↗
Responses of canine coronary arteries to transmural electrical stimulation and nicotine.
In helical strips of dog coronary arteries contracted with prostaglandin F2 alpha, transmural electrical stimulation and nicotine elicited a transient relaxation. The response to electrical stimulation was abolished by tetrodotoxin, bretylium or pretreatment of the dogs with reserpine, and was potentiated by cocaine. Atropine was ineffective. The relaxations were abolished or converted to contractions by sotalol; the contraction was suppressed by phentolamine. The nicotine-induced relaxation was suppressed by hexamethonium, cocaine, bretylium and sotalol. Atropine and tetrodotoxin did not affect the response. Following pretreatment with reserpine, relaxant responses to nicotine were partly reduced; the remaining relaxations were suppressed by atropine, slightly inhibited by sotalol and potentiated by physostigmine. It may be concluded that electrical stimulation liberates norepinephrine from adrenergic nerves, which preferentially activates beta-adrenoceptors. The reuptake mechanism appears to function to inactivate liberated norepinephrine. Nicotine-induced relaxations are mediated mainly by liberated norepinephrine; however, as shown by the pretreatment with reserpine, the release of an acetylcholine-like substance may also be involved.
Animals↗
Different responsiveness of a variety of isolated dog arteries to prostaglandin D2.
The addition of prostaglandin (PG) D2 contracted helical strips of dog cerebral, coronary, renal and femoral arteries; the contraction was greatest in cerebral arteries. The contractile response of cerebral arteries was potentiated by aspirin and attenuated by polyphloretin phosphate. In the arterial strips contracted with PGF2 alpha, PGD2 elicited a concentration-related relaxation; the relaxation was greatest in mesenteric arteries. In mesenteric arterial strips contracted with norepinephrine, a lesser degree of relaxation was induced, and in the K+-contracted arteries, only a contraction was induced. Treatment with PGD2 attenuated the contractile response of cerebral and mesenteric arteries to PGF2 alpha or PGE2; this inhibitory effect was approximately 10 times greater in mesenteric arteries. However, the response to serotonin (for cerebral arteries) or norepinephrine (for mesenteric) was unaffected. It may be concluded that the heterogeneity of responses to PGD2 of a variety of dog arteries is due to different contributions of vasoconstrictor and vasodilator mechanisms. PGD2 appears to share the mechanism underlying arterial contraction with PGF2 alpha and PGE2, and interferes with the effect of these PG's possibly on receptor sites.
Animals↗
Relaxant responses to transmural stimulation and nicotine of dog and monkey cerebral arteries.
In helical strips of dog and monkey cerebral arteries contracted with prostaglandin F2 alpha, transmural stimulation and nicotine produced relaxations that were abolished by tetrodotoxin and hexamethonium, respectively. These responses were attenuated by quinidine, whereas relaxations of dog coronary arteries to transmural stimulation and isoproterenol were unaffected. Treatment with vasoactive intestinal polypeptide (VIP) and substance P (SP) abolished the relaxant response of cerebral arteries to repeated applications of VIP and SP, respectively; however, after VIP or SP, a normal relaxant response to transmural stimulation or nicotine was produced. Aminophylline suppressed relaxations induced by ATP but not by nerve stimulation. VIP, SP, and adenosine 5'-triphosphate (ATP) relaxed dog cerebral arteries; the responses were unaffected by quinidine. However, only VIP and ATP relaxed monkey cerebral arteries, and SP contracted the arteries. Acetylcholine contracted monkey arteries, in which transmural stimulation produced a relaxation. It may be concluded that nerves innervating the cerebrospinal wall are stimulated electrically and chemically by nicotine, resulting in the arterial relaxation. However, a vasodilator transmitter was not identified. Quinidine appears to selectively antagonize the action of the transmitters on cerebroarterial smooth muscle.
Animals↗
Responses to adenine nucleotides and related compounds of isolated dog cerebral, coronary and mesenteric arteries.
In helically cut strips of dog cerebral, coronary and mesenteric arteries contracted with prostaglandin F2 alpha, adenosine, AMP, ADP, ATP and cyclic AMP produced dose-related, persistent relaxation. On the basis of ED50S, the relaxant effect seen in cerebral arteries was in the order of AMP, ADP, ATP greater than adenosine, cyclic AMP greater than aderine, dibutyryl cyclic AMP greater than inosine. On the basis of maximum relaxations, the effect was in the order of adenine, dibutyryl cyclic AMP greater than or equal to adenosine, AMP, ADP, ATP greater than cyclic AMP, inosine. The relaxant responses to adenosine, AMP, ADP, ATP and cyclic AMP were attenuated by treatment with aminophylline, whereas the relaxations induced by dibutyryl cyclic AMP, adenine and inosine were not altered. It is concluded that adenosine, AMP, ADP and ATP, but not adenine and inosine, appear to share receptors underlying arterial relaxations, and the cyclic AMP-induced relaxation does not derive from increments in cellular cyclic AMP. Treatment with aspirin did not alter the relaxant effect of ADP, adenosine and adenine, suggesting that the release of vasoactive prostaglandins is not involved.
Adenosine↗
Mechanism of action of carbocyclic thromboxane A2 and its interaction with prostaglandin I2 and verapamil in isolated arteries.
Carbocyclic thromboxane A2 (10(-9) to 10(-7) M) produced a concentration-dependent contraction of helical strips of dog cerebral, coronary, mesenteric, renal, and femoral arteries and of monkey cerebral, coronary, and mesenteric arteries. Contraction induced by low concentrations of carbocyclic thromboxane A2 tended to be greater in cerebral arterial strips. Even after 60 minutes of exposure to Ca++-free media, approximately one-half of the contractile response of dog cerebral and mesenteric arteries to 10(-8) M carbocyclic thromboxane A2 was retained. The contractile response was attenuated by diphloretin phosphate, a prostaglandin antagonist, and was potentiated by aspirin. In dog cerebral arterial strips contracted with carbocyclic thromboxane, the relaxant response to prostaglandin I2 was less than the response seen in mesenteric and coronary arteries, whereas, in contrast, the response to verapamil was greater in cerebral arteries. Concentration-relaxation curves for papaverine did differ appreciably. It may be concluded that contractions induced by carbocyclic thromboxane are associated with the release of Ca++ from intracellular storage sites and, in addition, the increase in transmembrane Ca++ influx. Greater susceptibility of cerebral arteries to verapamil may indicate that the Ca++ antagonist is of use to relieve the persistent contraction of cerebroarterial smooth muscle. Prostaglandin I2 appears to counteract effectively the action of potent vasoconstrictors, such as thromboxane A2 and its carbocyclic analog, in various vascular beds.
Animals↗
Length-passive tension relationships in cerebral and peripheral arteries isolated from spontaneously hypertensive and normotensive rats.
The length-passive tension relationship was compared in helically-cut strips of the basilar, renal and mesenteric arteries and the aorta isolated from Kyoto Wistar (WKY) rats and stroke-resistant (SHRSR) and stroke-prone spontaneously hypertensive rats (SHRSP). Passive tension developed by the same magnitude of rapid stretch was greater in basilar arteries than in the other arteries and aortae. The length-tension curve shifted toward the tension axis in basilar arteries and aortae isolated from SHRSP as compared with those isolated from WKY, whereas the curves in mesenteric and renal arteries from SHRSP, SHRSR and WKY were not significantly different. It is concluded that the distensibility of various arteries isolated from rats differs, and the cerebral artery becomes less distensible during the persistence of hypertension and the rat become prone to stroke.
Animals↗