Biomedical subjects

F J Miranda

Publications and source records attributed to F J Miranda.

At least 19 recordsLinked to original sources

PubMed2001

Diabetes potentiates acetylcholine-induced relaxation in rabbit renal arteries.

The response of rabbit renal arteries to acetylcholine and its endothelial modulation in diabetes were investigated. Acetylcholine induced concentration-related endothelium-dependent relaxation of renal arteries that was significantly more potent in diabetic rabbits than in control rabbits. Pretreatment with N(G)-nitro-L-arginine (L-NOArg), indomethacin, or L-NOArg plus indomethacin induced partial inhibition of acetylcholine-induced relaxation. Inhibition induced by L-NOArg plus indomethacin was significantly higher in arteries from diabetic rabbits than in arteries from control rabbits. In renal arteries depolarised with KCl 30 mM and incubated with L-NOArg plus indomethacin, acetylcholine-induced relaxation was almost abolished in both groups of rabbits and this response was not different from that obtained in arteries without endothelium. Sodium nitroprusside induced concentration-dependent relaxation of renal arteries from control and diabetic rabbits without significant differences between the two groups of animals. These results suggest that diabetes potentiates the acetylcholine-induced relaxation in rabbit renal arteries. Increased release of nitric oxide and prostacyclin could be responsible for the enhanced relaxant potency of acetylcholine in diabetes.

Acetylcholine↗

PubMed2000

Diabetes-induced changes in endothelial mechanisms implicated in rabbit carotid arterial response to 5-hydroxytryptamine.

The influence of diabetes on endothelial mechanisms implicated in the response of isolated rabbit carotid arteries to 5-hydroxytryptamine (5-HT) was studied. 5-HT induced a concentration-dependent contraction that was potentiated in arteries from diabetic rabbits with respect to that in arteries from control rabbits. Endothelium removal potentiated 5-HT contractions in arteries from both control and diabetic rabbits but increased the maximum effect only in arteries from diabetic rabbits. Incubation of arterial segments with N(G)-nitro-L-arginine (L-NA) enhanced the contractile response to 5-HT. This L-NA enhancement was greater in arteries from diabetic rabbits than in arteries from control rabbits. Aminoguanidine did not modify the 5-HT contraction in arteries from control and diabetic rabbits. Indomethacin inhibited the 5-HT-induced response, and this inhibition was higher in arteries from control rabbits than in arteries from diabetic rabbits. In summary, diabetes enhances the sensitivity of the rabbit carotid artery to 5-HT. In control animals, the endothelium modulated the arterial response to 5-HT by the release of both nitric oxide (NO) and a vasoconstrictor prostanoid. Diabetes enhances endothelial constitutive NO activity and impairs the production of the endothelial vasoconstrictor.

Animals↗

PubMed2000

Influence of experimental diabetes on regulatory mechanisms of vascular response of rabbit carotid artery to acetylcholine.

The purpose of this study was to analyse the influence of experimental diabetes on vascular response of rabbit carotid artery to acetylcholine (Ach). We compared the Ach-induced relaxant response of isolated arterial segments obtained from both control and diabetic animals. To assess the influence of the endothelium, this cell layer was mechanically removed in some of the arterial segments ("rubbed arteries") from each experimental group. Ach induced a concentration-related endothelium-mediated relaxation of carotid artery from control rabbits that was significantly higher with respect to that obtained in diabetic animals. Pre-treatment with N(G)-nitro-L-arginine (L-NA) induced a concentration-dependent inhibition of relaxant response to Ach, which was significantly higher in carotid arteries isolated from diabetic rabbits. Incubation of rubbed arteries with L-NA almost abolished the relaxant response to Ach in arterial segments from both control and diabetic animals. Indomethacin potentiated Ach-induced response of carotid arteries from control rabbits, without modifying that obtained in those from diabetic animals. Aminoguanidine did not significantly inhibit the relaxant action of Ach in arterial segments from either control or diabetic rabbits. These results suggest that diabetes impairs endothelial modulatory mechanisms of vascular response of rabbit carotid artery to Ach. This endothelial dysfunction is neither related with a lower release of nitric oxide (NO) or prostacyclin. Diabetes impairs the production of some arachidonic acid vasoconstrictor derivative. There has been observed an increased modulatory activity of NO, but this is not related with the expression of an inducible isoform of NO synthase.

Acetylcholine↗

PubMed1998

Comparative analysis of the vascular actions of diterpenes isolated from Euphorbia canariensis.

We have analysed the effects of 2,3-diepiingol 7,12-diacetate-8-isobutyrate (compound 1), ingenol-3-angelate-17-benzoate (compound 2), ingenol-3-angelate-17-benzoate-20-acetate (compound 3) and 3,5,7,8,9,15-hexahydroxyjatropha-6(17),11-dien-14-one-5,8-bi s(2-methylbutyrate)-7-(2-methylpropionate) (compound 4), four diterpenes isolated from E. canariensis, on the isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to these compounds were obtained cumulatively in both arteries at resting tension and active tone (KCl, 50 mM). At resting tension a concentration-dependent contraction was induced by the four compounds. In the basilar artery the order of potency was 3=1>2=4, without significant differences between Emax values. In the carotid artery the order of potency was 3>2=1=4 and there were no significant differences between the Emax (maximum effect) values of compounds 1-3, all of which were higher than that of compound 4. In pre-contracted basilar artery compounds 1-3 induced concentration-dependent relaxation and compound 4 was almost ineffective; the order of potency was 3>2=1 without significant differences between Emax values. In the carotid artery with active tone the four compounds tested induced further contractions; the order of potency was 3>2=4>1 without significant differences between Emax values. These results show that the four diterpenes are potent active substances in rabbit basilar and carotid arteries and that there are regional differences between their action. The four compounds tested contract basilar and carotid arteries at resting tension. Compounds 1-3 relax pre-contracted basilar artery but not carotid artery.

Animals↗

PubMed1997

Impairment of the modulatory role of nitric oxide on the endothelin-1-elicited contraction of cerebral arteries: a pathogenetic factor in cerebral vasospasm after subarachnoid hemorrhage?

OBJECTIVE: Nitric oxide (NO) and endothelin-1 (ET-1) are two endothelium-derived factors probably involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). Our aim was twofold, i.e., to ascertain whether endothelial and nonendothelial NO modulates the contractile response of cerebral arteries to ET-1 and to analyze whether this relationship might be impaired after experimental SAH. METHODS: Rings of middle cerebral artery from goats in the control group and from goats with SAH were set up for isometric tension recordings. SAH was induced 3 days before the experiments by infusion of 10 ml of autologous arterial blood through a catheter previously inserted into the subarachnoid space (basal cistern). In goats in the control group, the response to ET-1 was obtained as follows: 1) in control arteries (unrubbed and nonincubated arteries); 2) in rubbed arteries (arteries in which the endothelium was mechanically removed); 3) during incubation with NG-nitro-L-arginine (L-NOArg) alone or plus L- or D-arginine; and 4) in rubbed arteries plus incubation with L-NOArg. In goats with SAH, that response was obtained in control arteries, rubbed arteries, and during incubation with L-NOArg. Specimens of middle cerebral artery were processed for transmission electron microscopy study. RESULTS: In goats in the control group, ET-1 elicited concentration-dependent contraction of the middle cerebral artery that was significantly potentiated after endothelium denudation or during incubation with L-NOArg. The latter effect was reversed by L-arginine but not by D-arginine. Combined endothelium denudation and incubation with L-NOArg produced a contractile response to ET-1 significantly higher than that induced by each treatment separately. Hyperreactivity to ET-1 was observed in goats with SAH. Endothelium denudation did not alter the enhanced response to ET-1, but it was further significantly increased after incubation with L-NOArg. CONCLUSION: These results demonstrate that an ET-1-NO interaction exists in control cerebral arteries in such a way that endothelial and nonendothelial NO partially counteract the contractile response to ET-1 and that although SAH did not modify the effect of nonendothelial NO, the absence of endothelial NO after SAH may contribute to the hyperreactivity of cerebral arteries to ET-1 and, thereby, to the development of cerebral vasospasm.

Animals↗

PubMed1997

Analysis of rabbit vascular responses to DBI, an ingol derivative isolated from Euphorbia canariensis.

We have analysed the effects of 7,12-O-diacetyl-8-O-benzoil-2,3-diepiingol (DBI), an ingol derivative isolated from E. canariensis, on isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to DBI (10(-8) - 3 x 10(-5) M) were obtained cumulatively in both arteries at resting tension and active tone (KCI, 50 mM). At resting tension, DBI induced a concentration-dependent contraction, which was not inhibited in Ca(2+)-free medium. H7 (1-(5-isoquinoline sulphonyl)-2-methylpiperazine dichloride) (10(-4) M) inhibited the DBI-induced contraction both in basilar and in carotid arteries. Calmidazolium (10(-4) M) inhibited the maximum contraction of the carotid artery to DBI, and completely abolished the response in the basilar artery. In pre-contracted basilar arteries DBI induced a concentration-dependent relaxation that was not modified by incubation with NG-nitro-L-arginine (L-NOARG; 10(-5) M) or indomethacin (10(-5) M). In the carotid artery with active tone DBI induced further contractions, which were not significantly modified by L-NOARG (10(-5) M) and were potentiated by indomethacin (10(-5) M). These results suggest that DBI contracts rabbit basilar and carotid arteries by a mechanism that is independent of extracellular Ca2+ and involves the participation both of protein kinase C and of calmodulin. DBI relaxes basilar but not carotid arteries by a mechanism independent of the liberation of nitric oxide and prostacyclin. In the carotid artery prostacyclin but not nitric oxide partially counteracts the contractile action of DBI.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1997

In vitro weathering of selected direct esthetic restorative materials.

Reflectance spectroscopy measurements were used to compare the degree of surface color shift in two classes of visible light-cured resin composites (hybrid and small-particle) and a glass-ionomer restorative. The weathering times investigated were 0, 100, 200, 300, and 400 hours. Environmental factors of heat, ultraviolet light, and moisture were used to affect the surface integrity of the restoratives. The parameter of delta E * ab (overall color difference) of the CIELAB system for measuring small color differences was used. Chroma changes [delta C * ab] and hue differences [delta H * ab] were also determined. Color shifts, chroma changes, and hue differences were observed for all restorative materials evaluated, regardless of the weathering conditions or time intervals imposed. Glass-ionomer cement demonstrated a significantly greater degree of color shift than did the resin composites. There was no significant difference in the amount of overall color change between the two resin composites, although the difference in change in lightness was significant.

Color↗

PubMed1996

Modulatory role of endothelial and nonendothelial nitric oxide in 5-hydroxytryptamine-induced contraction in cerebral arteries after subarachnoid hemorrhage.

OBJECTIVE: Endothelial dysfunction is claimed to play a role in the pathogenesis of delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). We have examined the effect of experimental SAH on the modulatory action of endothelial and nonendothelial nitric oxide (NO) in the contractile response of goat middle cerebral artery to 5-hydroxytryptamine (5-HT). METHODS: We compared the 5-HT-induced contractile responses of cerebral arteries from control goats and from goats with SAH that had been experimentally induced 3 days earlier by delivery of autologous arterial blood into the subarachnoid space. Contractile responses were examined by recording the isometric tension in isolated cerebral arteries. To assess the influence of endothelium, this cell layer was mechanically removed in some of the arteria, segments (rubbed arteries) from both control goats and goats with SAH. RESULTS: In arteries from control goats, contractile responses to 5-HT were significantly higher in rubbed arteries than in arteries with intact endothelium; 5-HT-induced contractions were significantly enhanced by a competitive inhibitor of NO synthesis, NG-nitro-l-arginine, in arteries both with and without endothelium. In arteries from goats with SAH, 5-HT contracted cerebral arteries without showing significant differences between segments with endothelium and those that had been rubbed; in both cases, 5-HT-induced contractions were significantly higher than those obtained in arteries from control goats. NG-Nitro-l-arginine significantly enhanced the contractile response to 5-HT of cerebral arteries from goats with SAH. CONCLUSION: These results suggest that cerebral arteries after SAH exhibit hyperreactivity to 5-HT via a mechanism that involves the absence of the modulatory role of endothelial NO, that SAH does not modify the modulatory role of nonendothelial NO, and that impairment of the modulatory action of endothelial NO on vascular responses to 5-HT could contribute to the pathogenesis of cerebral vasospasm after SAH.

Animals↗

PubMed1996

Effects of equivalent abrasive grit sizes utilizing differing polishing motions on selected restorative materials.

The effects on surface roughness of three specific classifications of abrasive motion during the polishing of selected amalgam and resin composite materials were evaluated with a profilometer. Equivalent grit sizes were used to evaluate the character of the surface created by each class of abrasive motion. The motions investigated were rotary (diamond), planar (sandpaper disk), and reciprocal (reciprocating handpiece). Fine, medium, and coarse abrasives were used with each motion. Average roughness values for each abraded specimen were used to compare the effects of the type of motion on the surface. Results indicated that, among all of the combinations of motions and abrasive grits evaluated, the planar motion produced significantly lower surface roughness values on both amalgam and resin composite surfaces.

Composite Resins↗

PubMed1996

Resin-modified glass ionomers: a new option in restorative dentistry.

New dental materials and products are constantly being introduced in hopes of replacing or improving established materials. Although this onslaught of dental innovation can eventually lead to major improvements in the ease and success of clinical dentistry, it also presents a nightmare for the practitioner wishing to keep pace with these products. The introduction of the resin-modified glass ionomers at first glance appears to offer some very promising applications. Only time and clinical trials will give practitioners a true account of their benefits as well as their shortcomings.

Composite Resins↗

PubMed1995

Characterization of 5-hydroxytryptamine receptors in goat cerebral arteries.

1. In isolated goat middle cerebral artery segments, 5-hydroxytryptamine (5-HT, 10(-8)-3 x 10(-5) M) elicited concentration-dependent contractions with EC50 = 2.1 (1.9-2.5) x 10(-7) M and Emax = 64 +/- 2% of 50 mM KCl-induced contraction. 2. Several 5-HT receptor agonists were used: (a) the agonist of 5-HT2 receptors alpha-methyl-5-hydroxy-tryptamine (10(-7)-3 x 10(-4) M) induced strong contraction (51 +/- 6%); (b) the selective agonists of 5-HT1 receptors sumatriptan (10(-8)-10(-5) M) and 5-carboxamidotryptamine (10(-9)-10(-4) M) and the agonist of 5-HT1A receptors 8-hydroxy-2-(di-n-propylamino)tetralin (10(-7)-3 x 10(-5) M) induced weak contractions (8, 18 and 14%, respectively); and (c) the agonist of 5HT3 receptors 2-methyl-5-hydroxytryptamine (3 x 10(-6)-10(-4) M) induced almost negligible contraction. 3. Pretreatment with the antagonist of 5-HT1A and 5-HT1B receptors cyanopindolol (10(-8), 10(-6) M), the antagonist of 5-HT1/5-HT2 receptors methysergide (10(-11), 10(-9) M) and the antagonist of 5-HT2 receptors ketanserin (10(-11), 10(-9) M) induced non-competitive inhibition of the concentration-response curve to 5-HT. The antagonist of 5-HT3 receptors 3-trophanyl-3,5-dichlorobenzoate (10(-7), 10(-5) M) did not inhibit the contractile curve to 5-HT. 4. These results suggest that 5-HT contracts the goat middle cerebral artery by acting mainly on 5-HT2 receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1994

Different effects of Mg2+ on endothelin-1- and 5-hydroxytryptamine-elicited responses in goat cerebrovascular bed.

Mg2+ influences the response of cerebral arteries to several agonists, but until now its effects on endothelin-1 (ET-1) had not been studied. We recorded and compared the responses of goat cerebrovascular bed to ET-1 and 5-hydroxytryptamine (5-HT) during various Mg2+ treatments. We performed experiments in vitro by recording isometric tension in isolated goat middle cerebral arteries and in vivo by recording cerebral blood flow (CBF) and other physiologic parameters in conscious goats. Cumulative addition of ET-1 (10(-11)-3 x 10(-8) M) and 5-HT (10(-9) -10(-5) M) contracted cerebral arteries concentration dependently in bath media containing 0 (Mg(2+)-free medium), 1 (control), and 10 mM Mg2+, but the influence of Mg2+ was different: Mg2+ deprivation increased sensitivity (EC50) and Mg2+ overload reduced contractility (Emax) of cerebral arteries to 5-HT, whereas the ET-1 response did not change in these conditions. Cumulative addition of Mg2+ (10(-4)-3 x 10(-2) M) at the active tone induced by ET-1 (10(-9) M) and 5-HT (10(-5) M) elicited concentration-dependent relaxations of cerebral arteries, but the relaxant response was lower at the ET-1 precontraction. Infusions of ET-1 (0.1 nmol/min) and 5-HT (10 micrograms/min) directly into the cerebroarterial supply of the unanesthetized goats elicited a sustained decrease in CBF and an increase in cerebral vascular resistance. Magnesium sulfate, administered as increasing doses (10-300 mg) in the same way increased CBF and decreased cerebral vascular resistance, although this effect was less on ET-1-induced than on 5-HT-induced cerebral vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Changes in the adrenergic mechanisms of cerebral arteries after subarachnoid hemorrhage in goats.

We have examined the effects of experimental subarachnoid hemorrhage (SAH), induced by delivering autologous blood into the subarachnoid space, on the adrenergic mechanisms of the goat cerebrovascular bed. To achieve this, the response to noradrenaline was recorded both in vivo, by measuring cerebral blood flow in unanesthetized animals, and in vitro, by recording isometric tension in isolated cerebral arteries. In addition, we checked the function of adrenergic innervation by measuring the tritium efflux evoked by electrical stimulation in cerebral arteries preloaded with [3H]-noradrenaline, and we examined this innervation by using both fluorescent and electron transmission microscopy. All studies were performed before and 3, 7, and 14 days after SAH. Injections of noradrenaline (0.1-10 micrograms) directly into the cerebro-arterial supply produced reductions in cerebral blood flow, with no concomitant changes in mean arterial blood pressure and heart rate, which were significantly enhanced (P < 0.01) 3 and 7 days after SAH and returned to control values 14 days after hemorrhage induction. In isolated cerebral arteries, noradrenaline (10(-8)-10(-4) mol/L) produced concentration-dependent contractions, which were also significantly enhanced (P < 0.05) 3 and 7 days after SAH and returned to control values in cerebral arteries obtained 14 days after SAH. On the other hand, increases in the release of tritium induced by electrical stimulation in cerebral arteries preloaded with [3H]-noradrenaline were significantly lower (P < 0.01) after SAH. Moreover, microscopical studies showed a reduction in catecholamine fluorescence and signs of sympathetic degeneration in some perivascular axons after SAH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗

PubMed1993

Endothelial modulation of 5-hydroxytryptamine-induced contraction in goat cerebral arteries.

1. In isolated goat middle cerebral artery segments, 5-hydroxytryptamine (5-HT, 10(-8) -3 x 10(-5)M) caused concentration-dependent contractions, with EC50 = 2.1 (1.9-2.5) x 10(-7) M and Emax = 60 +/- 2% of 50 mM KCl-induced contraction. 2. Mechanical removal of endothelium significantly increased the Emax (91 +/- 8%) and did not change the EC50 value of 5-HT-elicited contractions. 3. Incubation of unrubbed arteries with the irreversible inhibitor of EDRF, gossypol (10(-5) M), significantly increased the contractile response to 5-HT (Emax = 77 +/- 4%). 4. Incubation of unrubbed arteries with the competitive inhibitor of the NO synthesis, NG-nitro-L-arginine (L-NOARG) (10(-5) M), significantly enhanced the arterial response to 5-HT (Emax = 71 +/- 5%). The effects of L-NOARG were reversed by L-arginine (10(-4) M) but not by D-arginine (10(-4) M). 5. Pretreatment with the inhibitor of cyclooxygenase, indomethacin (10(-5) M), significantly increased the response of unrubbed arteries to 5-HT, with an Emax of 69 +/- 3%. 6. These results suggest that endothelium modulates the constrictor effect of 5-HT in goat cerebral arteries by producing both EDRF, probably NO, and prostacyclin.

Animals↗

PubMed1993

Changes in the cerebrovascular effects of endothelin-1 and nicardipine after experimental subarachnoid hemorrhage.

The role of endothelium-related factors in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH) has gained interest since the discovery of endothelin-1 (ET-1). We have examined, before and after SAH, the responsiveness of the cerebrovascular bed of the goat to ET-1, the sources of Ca2+ in ET-1-induced responses, and the ability of the Ca2+ entry blocker nicardipine to counteract them. Before SAH, injection of ET-1 into the cerebral circulation increased cerebrovascular resistance, thereby producing dose-dependent reductions in cerebral blood flow (CBF), which were prevented by nicardipine. In isolated middle cerebral arteries, ET-1 induced concentration-dependent contractions, which were equally inhibited in Ca(2+)-free medium (without or with ethylene glycol tetraacetic acid) and by the Ca2+ entry blocker nicardipine. On the third day after SAH, CBF was reduced by 28% and cerebrovascular resistance increased by 39%. At the same time, both ET-1-induced reductions in CBF and the constricting effects of ET-1 in vitro were enhanced. The ability of nicardipine to increase CBF and to inhibit the effects of ET-1 was impaired as a result of reduced dependence of cerebral arteries on extracellular Ca2+. On the seventh day after SAH, CBF and cerebrovascular resistance returned to control values, and effects of ET-1 became normal. It is suggested that the hyperreactivity to ET-1 of the cerebrovascular bed induced by SAH could have a role in the development of vasospasm, which could reduce the vascular effects of Ca2+ entry blockers after SAH.

Animals↗

PubMed1992

Comparison of the anticonstrictor action of dihydropyridines (nimodipine and nicardipine) and Mg2+ in isolated human cerebral arteries.

The isometric tension recorded from ring segments of branches of human middle cerebral artery was the parameter used to study the inhibition of spasmogen-induced contractions as model for cerebral vasospasm. Concentration-response curves to 5-hydroxytryptamine (10(-9)-3 x 10(-5) M) and prostaglandin F2 alpha (10(-7)-3 x 10(-5) M) were inhibited in Ca(2+)-free medium and in Ca(2+)-free medium to which EGTA (1 mM) had been added, respectively. Nimodipine (10(-7), 10(-5) M), nicardipine (10(-7), 10(-5) M) and Mg2+ (magnesium sulfate 10(-4), 10(-2) M) inhibited the 5-HT-elicited contractions, and this inhibition was similar for the highest concentrations tested. In contrast, nimodipine and nicardipine were more effective than Mg2+ to inhibit the prostaglandin F2 alpha-elicited contractions. Nimodipine (10(-9)-10(-5) M), nicardipine (10(-9)-10(-5) M) and Mg2+ (10(-5)-3 x 10(-2) M) relaxed the arteries precontracted with PGF2 alpha (10(-5) M), but nicardipine was the most potent relaxant drug. Because 5-hydroxytryptamine and prostaglandin F2 alpha may be involved in the pathogenesis of cerebral vasospasm, nimodipine, nicardipine, and Mg2+ could be used in the pharmacological treatment of this disorder. However, dihydropyridines (particularly nicardipine) are more potent anticonstrictors than Mg2+.

Adult↗

PubMed1992

Direct and neuromodulatory effects of histamine on isolated goat cerebral arteries.

1. The effects of histamine on isolated goat middle cerebral artery were examined using two experimental approaches: recording of isometric tension and measurement of [3H]-noradrenaline efflux. 2. Cumulative addition of histamine (10(-7)-3 x 10(-2)M) and 2-pyridylethylamine (2-PEA, 10(-6)-3 x 10(-2)M) produced concentration-dependent contractile responses. Preincubation with diphenhydramine (10(-7), 10(-6)M) or cimetidine (10(-7), 10(-6)M) competitively inhibited the histamine-induced contractile response. 3. Endothelium denudation enhanced the contractile effects of histamine. 4. Transmural electrical stimulation elicited contractions which were enhanced by histamine (10(-7)M), 2-PEA (10(-6)M) and dimaprit (10(-4)M). Diphenhydramine (10(-5)M) inhibited the action of histamine, but cimetidine did not. 5. Noradrenaline (10(-8)-10(-4)M) elicited concentration-dependent contractions which were unaffected by histamine (10(-7)M). 6. In arteries preloaded with [3H]-noradrenaline, transmural electrical stimulation induced an increase in the tritium efflux, which was enhanced in the presence of histamine (10(-7)M). 7. Therefore, histamine contracts cerebral arteries via specific non-endothelial H1-receptors, and enhances perivascular adrenergic neurotransmission through specific presynaptic H1-receptors by a mechanism involving increases in noradrenaline release.

Animals↗

PubMed1992

Comparison of the contractile effects of endothelin-1 and sarafotoxin S6b in goat isolated cerebral arteries.

1. The effects of endothelium-derived endothelin-1 and snake venom-derived sarafotoxin S6b, peptides with striking structural and functional similarities, were examined and compared in isolated middle cerebral arteries of goats. 2. Endothelin-1 and sarafotoxin S6b contracted cerebral arteries in a concentration-dependent manner. The potency of endothelin-1 (EC50 = 4.9 (3.9-6.2) x 10(-10) M) was about ten times higher than that of sarafotoxin S6b (EC50 = 5.5 (4.4-6.9) x 10(-9) M). The tension returned to basal values after repeated washings and contraction with endothelin-1 could be reproduced. Endothelin-1 and sarafotoxin S6b induced further contraction in arteries precontracted with prostaglandin F2 alpha (10(-5) M). 3. Mechanical removal of the endothelium or incubation with indomethacin (10(-5) M) displaced the concentration-response curves to endothelin-1 and, more pronouncedly, to sarafotoxin S6b to the left. The maximum response to sarafotoxin S6b was also increased by either of these two treatments. 4. Incubation in 'nominally' Ca(2+)-free medium attenuated the vasoconstrictor response to endothelin-1 but not to sarafotoxin S6b, which was inhibited after incubation in Ca(2+)-free medium to which EGTA (10(-4) M) had been added. Pretreatment with caffeine (2 x 10(-2) M) in Ca(2+)-free medium abolished responses to endothelin-1 and sarafotoxin S6b. 5. Bay K 8644 (10(-10) M, 10(-8) M) enhanced and nicardipine (10(-10) M, 10(-8) M) inhibited in a concentration-dependent manner vasoconstrictor response to endothelin-1. Response to sarafotoxin S6b was only affected by 10(-8) M Bay K 8644 or nicardipine.6. It is concluded that endothelin-1 and sarafotoxin S6b are potent vasoconstrictors of goat cerebral arteries, having direct effects on smooth muscle which are counteracted by the endothelium through the release of a vasodilatator substance, probably prostacyclin. Both endothelin-l and sarafotoxin S6b depend on extracellular Ca2+ and on intracellular, caffeine-sensitive Ca2+ stores to develop vasoconstriction.However, endothelin-l depends to a larger extent than sarafotoxin S6b on free extracellular Ca2+.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗