Biomedical subjects

N C Nyborg

Publications and source records attributed to N C Nyborg.

At least 37 records · Page 2Linked to original sources

PubMed1991

Role of the endothelium in acetylcholine-induced relaxation and spontaneous tone of bovine isolated retinal small arteries.

Acetylcholine induced a variable concentration-dependent relaxation of bovine isolated retinal small arteries contracted with PGF2 alpha. The acetylcholine-mediated relaxation was linearly related to the sodium nitroprusside-induced relaxation, suggesting that the endothelium is well preserved in the vessels and that the variable effect of acetylcholine is due to variations in the soluble guanylate-cyclase enzyme activity in the smooth muscle. The vessels became desensitized to acetylcholine by repeated exposures. L-arginine and indomethacin did not abolish the desensitization. The vessels also became desensitized to the direct smooth muscle relaxing effect of sodium nitroprusside, indicating that desensitization to the endothelium-dependent relaxation by acetylcholine is related primarily to the vascular smooth muscle cells. Atropine, methylene blue and removal of endothelium abolished the acetylcholine-induced relaxation completely, whereas indomethacin had no inhibitory action on the acetylcholine-induced relaxation, suggesting that acetylcholine mediates release of EDRF (nitric oxide: NO) through stimulation of muscarinic receptors. Methylene blue contracted endothelium intact retinal arteries but a spontaneous tone was not present in endothelial denuded arteries. This may indicate a basal release of both a contractile factor, e.g. endothelin, and a relaxing factor. NO, form the retinal endothelium. The results demonstrate that endothelial-derived factors may participate in normal as well as pathophysiological regulation of retinal vascular smooth muscle tone.

Acetylcholine↗

PubMed1991

Calcitonin gene-related peptide is a potent vasodilator of bovine retinal arteries in vitro.

Calcitonin gene-related peptide (CGRP) invariably induced a slow acting but potent relaxation of bovine retinal small arteries contracted with PGF2 alpha. Maximal relaxation obtained was 93% and 96% with a pD2-value of 8.97 and 8.86 for rat and human CGRP, respectively; thus the bovine retinal arteries cannot discriminate between CGRP from these two species. The CGRP-induced relaxation was reversible. Substance P was without effect on retinal arteries contracted with PGF2 alpha. Bradykinin relaxed 4 of 18 vessels tested in the concentration range of 11(-11)-10(-8) M whereas the vessels were contracted again at 3 x 10(-8) M. Bradykinin was without effect in the remaining 14 vessels. None of the peptides had a contractile effect on retinal arteries kept relaxed in normal buffer solution. Capsaicin 3 x 10(-5) M induced a relaxation comparable to that obtained by 10(-9) M of CGRP. The capsaicin-induced relaxation was reproducible and it was concentration dependently inhibited by ruthenium red which suggests that capsaicin releases CGRP in the arterial wall. The results indicate that CGRP has a powerful relaxing effect on the retinal vasculature indicating a role for CGRP in ocular blood flow regulation.

Animals↗

PubMed1991

Influence of the endothelium on histamine-induced relaxation of rat middle cerebral arteries in vitro.

Histamine relaxed PGF2 alpha-precontracted rat isolated middle cerebral arteries (ID approximately 230 microns) concentration dependently with a pD2 of 5.31 (EC50: 5 x 10(-6) M). Cimetidine induced a concentration-dependent rightward shift of the histamine concentration-response curve of endothelium-intact arteries. The slope of the Schild plot was indistinguishable from unity, and the estimated pA2 for cimetidine was 6.14. The selective H2-receptor agonist dimaprit induced a concentration dependent relaxation of the cerebral arteries similar to that induced by histamine. This indicates that the histamine receptor mediating the relaxation in rat middle cerebral arteries belongs to the H2-receptor subtype. 2-Pyridylethylamine, a selective H1-receptor agonist, induced a small concentration-dependent contraction of the arteries with a pD2 of 4.16. Mepyramine, a selective H1-receptor antagonist had no potentiating effect on the relaxation induced by histamine, suggesting either that the contractile effect of 2-pyridylethylamine is nonselective or that H1 receptors mediating contraction are of minor importance for the overall histamine response. The selective H3-receptor agonist, (R)-alpha-methylhistamine, was without effect in a specific concentration range (10(-7)-10(-5) M) excluding participation of H3 receptors in the histamine-induced relaxation of these vessels. Indomethacin did not affect the vessel response to histamine, but removal of the endothelium and treatment of endothelium-intact arteries with 3 x 10(-6) M methylene blue induced a similar 0.5 log rightward shift of the histamine concentration-response curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

(+)-S-12967 and (-)-S-12968: 1,4-dihydropyridine stereoisomers with calcium channel agonistic and antagonistic properties in rat resistance arteries.

1. The actions of (+)-S-12967 and (-)-S-12968 two isomers of a new 1,4-dihydropyridine (DHP) derivative, were studied on 125 mM K(+)-, Ca(2+)- and noradrenaline-induced contractions in rat isolated mesenteric resistance arteries and compared to those of nifedipine. 2. The action of (+)-S-12967 and (-)-S-12968 was slow in onset in contrast to nifedipine. Both isomers had a dual contractile and relaxant action in arteries contracted with 125 mM K+; however, the (-)-isomer was about 300 times more potent than the (+)-isomer. The response to 125 mM K+, being depressed by 70%, recovered within 20 to 30 min for all DHP derivatives. All vessels were treated with 1 x 10(-6) M phenoxybenzamine thus excluding the possibility that the contraction is mediated by activation of amine-receptors. 3. Both (+)-S-12967 and (-)-S-12968 at low concentrations potentiated responses induced by Ca2+ in arteries activated by 125 mM K+ and inhibited the responses at higher concentrations. (+)-S-12967 and (-)-S-12968 had no contractile action in arteries kept in normal buffer. Nifedipine had only an inhibitory action on vessel responses to 125 mM K+ and Ca2+. 4. Both isomers and nifedipine depressed the maximal vessel response to noradrenaline by about 20% and 44%, respectively. 5. The results confirm that DHP calcium antagonists selectively inhibit vascular smooth muscle responses induced by high potassium and that the potency of 1,4-DHP isomers may vary considerably. Furthermore, since the agonistic/antagonistic properties on the calcium channel were shared by both stereoisomers of the 1,4-DHP molecule and apparently dependent on their concentration and the vascular smooth muscle membrane potential, it suggests that the agonistic action of 1,4-DHPs may be ascribed to functional characteristics of their binding site regulating the Ca2l -channel.

Animals↗

PubMed1991

Heterogeneous involvement of endothelium in calcitonin gene-related peptide-induced relaxation in coronary arteries from rat.

1. The effects of rat- and human-CGRP and capsaicin were studied in isolated rings of rat proximal epicardial (PC) and distal intramyocardial (DC) coronary arteries. 2. The relaxing effect of rat-CGRP was dependent on the level of vessel tone induced by prostaglandin F2 alpha (PGF2 alpha) in PC but not in DC arteries. Submaximally contracted DC and PC arteries were more sensitive to rat- than human-CGRP. There was no difference in sensitivity to rat- and human-CGRP between PC and DC arteries. 3. Substance P elicited a small relaxation only in 4 of the 6 PC arteries tested. PC and DC arteries were concentration-dependently relaxed by capsaicin. The relaxation was partly inhibited by ruthenium red, thus suggesting that capsaicin causes specific release of CGRP from sensory nerve endings in rat coronary arteries. 4. The relaxant effect of rat-CGRP was antagonized by endothelium removal and indomethacin but not methylene blue in endothelium-intact PC arteries. The relaxation in DC arteries was not affected by any of these treatments, indicating a heterogeneous involvement of the endothelium in CGRP-mediated coronary vasodilatation and the release of a cyclo-oxygenase product in PC arteries in rats. 5. Glibenclamide had no inhibitory effect on the CGRP-induced relaxation of PC and DC arteries, thus excluding the involvement of glibenclamide-sensitive K(+)-channels in the mechanism of action of CGRP in rat coronary arteries.

Acetylcholine↗

PubMed1991

Ageing is associated with increased 5-HT2-receptor affinity and decreased receptor reserve in rat isolated coronary arteries.

1. The 5-hydroxytryptamine (5-HT)-receptor subtype and affinity for 5-HT was determined in large and small coronary arteries isolated as ring segments from the proximal and distal part of the left coronary artery of 3 month (young) and 2-year old (old) rats. 2. Ketanserin induced a rightward shift of the 5-HT concentration-response curve in both proximal and distal coronary arteries from young rats. The slopes of the Schild-plots were indistinguishable from unity and the estimated pA2 values were 9.11 and 9.27 for proximal and distal coronary arteries, respectively. These data indicate a homogeneous population of 5-HT2-like receptors in the coronary arteries. 3. The contractile effect of 5-HT as well as the sensitivity to 5-HT was greater in proximal and distal coronary arteries from old than from young rats. 4. The apparent 5-HT2-receptor affinity, -log(KA[M]), and fractional receptor-occupancy for relative responses between 10% and 90% of maximum was determined by partial irreversible inhibition of the 5-HT2-receptors with phenoxybenzamine. 5. Ageing was associated with an increase in 5-HT2-receptor affinity for 5-HT in both proximal and distal coronary arteries, whereas the fractional receptor occupancy for half-maximal response to 5-HT decreased with age. 6. 5-HT2-receptor affinity for 5-HT could account for the 5-HT sensitivity of distal coronary arteries in both young and old rats but not in proximal coronary arteries as the slope of the regression line of plots of 5-HT2-receptor affinity vs. sensitivity was indistinguishable from unity in only the distal vessels. 7. The 5-HT2-receptor affinity for 5-HT was linearly correlated to the fractional receptor occupancy for half maximal response, suggesting that the 5-HT2-receptor reserve or density down-regulates the receptor affinity for 5-HT. 8. The results indicate that the increase in 5-HT sensitivity and contractile effect in rat coronary arteries rely upon an increase in both 5-HT2-receptor agonist affinity and efficiency of the excitation-contraction coupling process in the vascular smooth muscle.

Aging↗

PubMed1991

Regional heterogeneity in the contractile and potentiating effects of neuropeptide Y in rat isolated coronary arteries: modulatory action of the endothelium.

1. Neuropeptide Y (NPY) induced a concentration-dependent contraction of isolated rings of proximal epicardial (PC) and distal intramural (DC) coronary arteries of the rat, with an EC50 of ca. 1 x 10(-7) M. The NPY-induced contraction at 3 x 10(-7) M was significantly smaller in PC than DC arteries: 34% vs. 55% of the 125 mM K(+)-induced response, respectively. 2. NPY (2 x 10(-8) M) increased the sensitivity to noradrenaline (NA) and 5-hydroxytryptamine (5-HT) more in PC (4.2 and 2.8 fold, respectively) than in DC arteries (2.2 and 1.4 fold, respectively). The maximal contractile response to NA and 5-HT was increased more in DC (43% and 29%, respectively) than in PC arteries (20% and 12%, respectively). 3. Removal of the endothelium increased the sensitivity and maximal response to NPY as well as the spontaneous myogenic tone in PC but not in DC arteries. NPY had no relaxing effect on PC and DC arteries submaximally contracted with 10(-6) M prostaglandin F2 alpha, suggesting that spontaneous rather than stimulated release of endothelium-derived relaxing factor (EDRF) depresses the contractile action of NPY in PC arteries. 4. The results indicate a heterogeneity in the contractile and potentiating action of NPY in rat coronary arteries depending on size or location in the coronary circulation.

Animals↗

PubMed1991

Histamine induces endothelium-dependent relaxation of bovine retinal arteries.

The effect of histamine on bovine isolated retinal small arteries (internal diameter, approximately 240 microns) was studied. Histamine induced a concentration-dependent relaxation in 43 of 53 vessels. The histamine-induced relaxation involves primarily activation of H1-receptors, with H2-receptors also affected as evidenced by the effect of selective histamine-receptor agonists and antagonists. The histamine-induced relaxation was dependent on the endothelium and seem to involve release of both endothelium-derived relaxing factor (EDRF) and a product which was inhibited by indomethacin, probably prostaglandin I2 (prostacyclin). The development of tachyphylaxis to the action of histamine seemed to rely on desensitization of the vascular smooth muscle cells to the relaxing effect of EDRF.

Acetylcholine↗

PubMed1991

Endothelin-1-induced contraction of bovine retinal small arteries is reversible and abolished by nitrendipine.

Endothelin-1 (porcine/human) induced a prompt, reversible, potent, concentration-dependent contraction of bovine isolated retinal small arteries (internal diameter, approximately 200 microns) with a concentration of endothelin-1 required to give half-maximal contraction of 2 x 10(-10) M. The maximal contraction induced by endothelin-1 was equal to 89% of the maximal contractile capacity. The vessel response to endothelin-1 was dependent on extracellular Ca2+. Withdrawal of extracellular Ca2+ or addition of nitrendipine, 10(-6) M, reduced the response of vessels contracted with 10(-9) M endothelin-1 by 80% and 75%, respectively. These results indicate that the endothelin-1-induced contraction of retinal arteries is dependent on an influx of extracellular Ca2+ through membrane potential-operated calcium channels. Endothelin-1, 10(-13)-10(-10) M, did not induce a relaxation of endothelium-intact arteries, indicating that endothelin-1 is incapable of releasing endothelium-derived relaxing factor in the retinal circulation. These results suggest that endothelin may participate in the regulation of retinal artery tone.

Acetylcholine↗

PubMed1990

5-Hydroxytryptamine does not release endothelium-derived relaxing factor in rat isolated coronary arteries.

Removal of the endothelium from isolated rat proximal and distal coronary artery segments shifted the 5-HT concentration-response curve to the left without affecting, the maximal contractile response. 5-HT had no relaxing effect in 10(-5) M prostaglandin F2 alpha-precontracted vessels with an intact endothelium in the presence of 10(-5) M ketanserin. The spontaneous myogenic tone increased in both proximal and distal coronary artery segments after the endothelium had been removed. Indomethacin (10(-5) M) reduced the response of the proximal coronary artery segments to 5-HT by 35% but indomethacin had no effect on the 5-HT concentration-response curve of the distal coronary artery segments. Indomethacin relaxed precontracted (40 mM potassium) proximal coronary artery segments independently of the presence of the endothelium, suggesting a non-specific relaxing effect of indomethacin in these arteries. It is concluded that rat coronary artery endothelium is unresponsive to 5-HT because it lacks 5-HT1 receptors. The increased 5-HT sensitivity and spontaneous myogenic tone of endothelium-denuded rat coronary arteries is probably due to the elimination of the relaxing stimulus mediated by spontaneously released endothelium-derived relaxing factor.

Acetylcholine↗

PubMed1990

Studies on the stereoselective effects of a novel 5-HT2 receptor antagonist on contractile responses of rat aorta.

The effect of the enantiomers of a novel 5-HT2 receptor antagonist, (+/-)-(1R,3S)-1-[2-[4-[3-(p-fluorophenyl)-1-indanyl]-piperazinyl] ethyl]-2-imidazolidinone, was studied on serotonin (5-HT), noradrenaline (NA), potassium (K+), and calcium (Ca2+)-induced contractions in isolated rat thoracic aorta. The enantiomers shifted the 5-HT, NA, K+, and Ca2+ concentration-response curves to the right in a concentration-dependent manner and depressed the maximal contractile responses. The (+)-enantiomer was a far more potent inhibitor of 5-HT-induced contractions than the (-)-enantiomer. The (+)-enantiomer and phentolamine, both at 10(-6) M, had equal inhibitory effects on NA-evoked contractions. The (+)-enantiomer was again more potent inhibiting NA-induced contractions than the (-)-enantiomer. Both enantiomers had an equieffective inhibitory effect on K+ and Ca2(+)-induced contractions. The results show that the 5-HT and alpha-adrenoceptor antagonism of the two enantiomers is stereoselective, the (+)-enantiomer being more potent than the (-)-enantiomer. In contrast the enantiomers had equal, nonstereoselective inhibitory effects on K+ and Ca2(+)-evoked contractions.

Animals↗

PubMed1990

Angiotensin II does not contract bovine retinal resistance arteries in vitro.

The effect of angiotensin II was studied in vitro on ring segments of bovine retinal resistance arteries (i.d. 126-271 microns) and posterior ciliary arteries (i.d. 207-1153 microns). Although the retinal resistance arteries were responsive to 5-hydroxytryptamine, prostaglandin F2 alpha, and changes in extracellular K(+)-concentration, they did not, in contrast to the posterior ciliary arteries, contract to cumulative or single doses of angiotensin II. In the latter arteries, angiotensin II induced a small concentration dependent contraction, 5% of maximal 125 mM K(+)-induced response, with a pD2-value of 9.3. The single addition of 10(-6) M angiotensin II increased the maximal vessel response of the posterior ciliary arteries three times to angiotensin II. Tachyphylaxis was pronounced in the posterior ciliary arteries, in which the response to angiotensin II could not be repeated. Indomethacin (10(-5) M), methylene blue (3 x 10(-6) M), or removal of endothelium did not make the retinal resistance arteries responsive to angiotensin II. Retinal arteries precontracted with 30 mM potassium did not respond to angiotensin II. Angiotensin II did not potentiate the 5-hydroxytryptamine- and noradrenaline concentration-response characteristics of both retinal resistance and posterior ciliary arteries. Although angiotensin II-receptors have been detected in bovine retinal vascular smooth muscle using radioligand-binding technique, the present results suggest that these receptors are non-functional in respect to regulation of retinal resistance artery tone.

Angiotensin II↗

PubMed1990

The level of spontaneous myogenic tone in isolated human posterior ciliary arteries decreases with age.

The spontaneous myogenic activity of rings of human posterior ciliary arteries was studied in vitro. All arteries from six patients had an intrinsic myogenic tone, which was dependent on extracellular calcium and inversely correlated with age. The myogenic tone was stable without rhythmic variations, except in one artery. The level of spontaneous myogenic tone was higher in vessels where the endothelium was removed than in normal arteries. Acetylcholine induced a complete and concentration dependent relaxation of endothelium-intact but not endothelium-denuded arteries. Indomethacin induced a small concentration dependent contraction of the arteries. Methylene blue did also contract the arteries concentration dependently. The experiments indicate that the myogenic tone of human posterior ciliary arteries is regulated by prostaglandin formation (prostacyclin?) as well as release of endothelium-derived relaxing factor in the arteries. The results indicate that the blood flow regulatory capacity of these arteries may be endangered by aging and endothelial damage, which could increase the probability of developing, e.g. ischemic damage of the optic nerve head.

Acetylcholine↗

PubMed1990

Active wall tension--length curve and morphology of isolated bovine retinal small arteries: important feature for pharmacodynamic studies.

The active and passive wall tension--internal circumference (diameter) relations of isolated ring segments of bovine retinal small arteries (i.d. ca. 200 microns) were studied in vitro using an isometric myograph. The active tension of the vessels (when fully activated with 10(-5) M 5-HT and 10(-5) M PGF2 alpha in high K(+)-saline) reached a maximum (1.2 N m-1) at an internal circumference, L0, where the passive tension (measured in Ca2(+)-free solution) were 0.89 N m-1. Below and above L0 the active tension fell linearly, the zero tension intercepts being 0.48 L0 and 1.61 L0. The passive wall tension rose exponentially as a function of the internal circumference (diameter) and was 43 times higher at 1.4 L0 than at L0. A small transient spontaneous contraction was observed after rapid stretch of the arteries. Papaverine and Ca2(+)-free solution did not change the wall tension of vessels stretched to L0, indicating absence of stable spontaneous myogenic tone in the vessels. Histological examination showed that the retinal artery media on average had three smooth muscle cell layers which in total were 12 microns thick. The media/lumen ratio was 7%. Smooth muscle cell volume was 1228 micron3, constituting about 72% of the media volume. The active wall tension--internal circumference relation and morphology of bovine retinal small arteries is generally equal to that of arteries of similar size from other species, but active force generation of the retinal vascular smooth muscle cells is considerably lower.

Animals↗

PubMed1990

Contractile and relaxing effects of arachidonic acid derivatives on isolated bovine retinal resistance arteries.

The reactivity of isolated ring segments (i.d. ca. 200 microns) of calf retinal resistance arteries to arachidonic acid derivatives were studied in vitro. Prostaglandin F2 alpha (PGF2 alpha) prostaglandin E2 (PGE2), and a thromboxane A2 analogue, 9,11-dideoxy-9 alpha,11 alpha-epoxymethane-prostaglandin F2 alpha, (TX2 alpha), induced a concentration dependent contraction with the order of potency: Tx2 alpha greater than PGE2 greater than PGF2 alpha with pD2-values (-log[EC50(M)]) of 6.88, 6.19 and 5.20, respectively. The maximal active tension development of the vessels induced by Tx2 alpha, PGE2 and PGF2 alpha, were 1.57 N m(-1), 1.05 N m(-1) and 1.19 N m(-1), corresponding to 94%, 57% and 67% of Emax, respectively. The active pressure development, and estimate of the maximum pressure which the vessels may be able to contract against in vivo, was 18 kPa, 12 kPa and 14 kPa (138, 89 and 110 mmHg) for Tx2 alpha, PGE2 and PGF2 alpha, respectively. Prostaglandin I2 (prostacyclin, PGI2) induced a concentration-dependent relaxation of retinal resistance arteries precontracted with 10(-5) M PGF2 alpha. The maximal relaxation induced by PGI2 amounted to 65% of the control vessel response induced by PGF2 alpha (1.27 N m(-1] with a -log[EC50(M)] value of 6.51. The results indicate that arachidonic acid derivatives are potent and effective agents capable of regulating bovine retinal resistance artery smooth muscle tension in vitro.

Animals↗

PubMed1990

Action of noradrenaline on isolated proximal and distal coronary arteries of rat: selective release of endothelium-derived relaxing factor in proximal arteries.

1. The effect of noradrenaline (NA) on the vascular smooth muscle and endothelial cells in isolated ring segments from the proximal and distal part of the left coronary artery (LCA) in rats was examined. 2. NA had a weak concentration-dependent contractile effect on proximal but relaxed distal segments of the LCA. The maximal NA-induced contraction of the proximal segments was doubled while the relaxation of the distal LCA segments was converted to a contraction after blockade of beta-adrenoceptors with propranolol 3 x 10(-6) M, thus indicating the presence of both alpha- and beta-adrenoceptors in the arteries, with dominance of alpha-adrenoceptors and of beta-adrenoceptors in the proximal and distal segments of the LCA, respectively. 3. The contractile effect of NA (beta-adrenoceptors blocked) was doubled in the proximal LCA segments after the endothelium was removed. Endothelial denudation had, in contrast, no potentiating effect on the contractile response of the distal arteries to NA. Both proximal and distal segments became more sensitive to the contractile action of NA after removal of the endothelium. 4. The spontaneous myogenic tone increased in both proximal and distal LCAs after endothelial removal, indicating spontaneous release of a relaxing endothelial factor in the vessels. 5. Following contraction with prostaglandin F2 alpha (PGF2 alpha), and in the presence of propranolol, 3 x 10(-6) M, and prazosin, 10(-6) M, NA induced an endothelium-dependent relaxation of only proximal but not distal segments of the precontracted LCA. The NA-induced relaxation of the proximal segments of the LCA was not altered by indomethacin 10- M but was completely abolished after incubation with methylene blue, 3 x 10-6 M, or following endothelium removal. These results are compatible with NA-induced release of EDRF in these arteries. 6. The selective alpha 2-adrenoceptor agonist, B-HT 933, only induced a weak relaxation of PGF2 alpha,-precontracted proximal (endothelium intact) LCA segments at a concentration of 10-4M. The NA-induced relaxation of these vessels was unaffected by incubating the vessels with 10- IM B-HT 933. The NA relaxation response curve was shifted ca 1.1 log unit to the right by rauwolscine, 1o- 6M, giving an estimated pA2-value of 7.12. The receptor through which NA activates the endothelium appears to be of an atypical alpha 2-subtype.

Acetylcholine↗

PubMed1990

Thrombin contracts isolated bovine retinal small arteries in vitro.

The effect of thrombin was tested in vitro on rings of bovine retinal small arteries (internal diameter approximately 200 microns). Cumulative addition of thrombin (0.001-10 units/ml) induced a variable concentration-dependent contraction of the retinal arteries. The contractions were slow in onset and reached a plateau after 5-8 minutes when thrombin was added cumulatively to the organ bath. Two vessels remained contracted greater than 1 hour after wash-out of thrombin. Maximum vessel contraction induced by thrombin was equal to 43% of the vessel Emax (1.36 N/m), with an effective concentration at the 50% level of 0.04 units/ml. Vessel contraction induced by 1 unit/ml of thrombin was, in contrast, transient, reaching a maximum within 2-4 minutes. Thereafter the vessel tension declined again almost back to baseline within the next 10-20 minutes. Contractions to thrombin could not be repeated nor could it be elicited with thrombin inactivated with heat or antithrombin-III. Treatment of vessels with 10(-6) M phenoxybenzamine had no effect on the thrombin-induced vessel response. These findings indicate that the contractile effect of thrombin depends on its catalytic activity. Indomethacin at a concentration of 10(-5) M did not affect the thrombin-induced vessel response. Methylene blue at a concentration of 3 X 10(-6) M potentiated the thrombin-induced response in the larger, greater than 200-microns diameter retinal arteries. The ensuing relaxation of the arteries, after maximal tone was reached, was slower than in the control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Angiotensin-II contracts isolated human posterior ciliary arteries.

The effect of angiotensin-II (A-II) was studied on ring segments of the terminal extraocular branches of the posterior ciliary artery isolated from human enucleated eyes. It induced a potent concentration-dependent contraction on top of the spontaneous myogenic tone of all arteries studied from five patients with the concentration required to give half-maximal response equal to 51 nM. The spontaneous tone and maximal increase in vessel wall tension induced by A-II was equal to 51% of Emax. The relative response and sensitivity to A-II was unchanged in three endothelial denuded vessels, but the spontaneous tone increased. The arteries became completely insensitive to A-II after one exposure. These results show an immediate direct contractile effect of A-II on human posterior ciliary arteries, but the development of pronounced tachyphylaxis indicates that A-II is probably not an important factor in reducing blood flow to the optic nerve head.

Aged↗