Biomedical subjects

D Prieto

Publications and source records attributed to D Prieto.

At least 55 records · Page 3Linked to original sources

PubMed1993

Catecholaminergic innervation of the equine ureter.

The aim of the present study was to determine the distribution and density of catecholaminergic nerve fibres and cells in the equine ureter by using immunohistochemical techniques to localise the enzyme tyrosine-hydroxylase (TH). TH-immunoreactive (TH-IR) nerve fibres entered the wall of the ureter as adventitial nerve trunks accompanying the blood vessels. These trunks repeatedly branched as they coursed through the muscular layer towards the epithelium, forming muscular, perivascular and subepithelial nerve plexuses. TH-IR nerve fibres were especially numerous in the pelvic and intravesical ends of the ureter. TH-IR cells have also been identified in the equine ureteral wall, usually grouped as adventitial and intramural nerve ganglia. The results of the present study demonstrated that the equine ureter, like that of other mammals, possesses a rich autonomic supply of catecholaminergic (TH-IR) nerve fibres. These morphological data support a role for the autonomic nervous system in the control of ureteral peristalsis.

Animals↗

PubMed1993

Heterogeneity of muscarinic receptors in lamb isolated coronary resistance arteries.

1. In vitro experiments in a microvascular myograph were designed to characterize postjunctional muscarinic receptors producing contraction both in the presence and absence of the endothelium in coronary resistance arteries (normalized diameter of 150-450 microns), isolated from the left ventricle of hearts from 3-6 month old lambs. Preferential muscarinic receptor antagonists were used to determine the receptor subtype: pirenzepine (M1 receptor), AFDX 116 (M2 receptor), 4-DAMP and pFHHSiD (M3 receptor). 2. The rank order of potency for muscarinic agonist-induced increases in tension in endothelium-intact preparations was oxotremorine-M = methacholine = acetylcholine (ACh) > carbachol. Removal of the endothelium increased the potency of ACh, but this procedure did not change either the sensitivity or maximal response to carbachol. 3. The contractile response to ACh was reproducible. Incubation with 3 x 10(-7)-3 x 10(-6) M pirenzepine induced non-parallel rightward shifts and depressed the maximum of the concentration-response curve to ACh in endothelium-intact arteries. The slope by Schild analysis was 2.9 +/- 0.8 (P < 0.05, n = 7). Atropine, AFDX 116, 4-DAMP and pFHHSiD produced parallel rightward shifts of the curves to ACh and the slopes of the Schild plots were not significantly different from unity. The pKB values for the antagonists from plots constrained to unity in endothelium-intact segments were: atropine (9.4), 4-DAMP (9.0), pFHHSiD (7.9) and AFDX 116 (6.2). 4. In endothelium-denuded arteries, pirenzepine, AFDX 116 and pFHHSiD caused concentration-dependent, parallel rightward displacements of the concentration-response curves to ACh and the slopes of the Schild plots were not significantly different from unity. The plots constrained to a slope of unity gave the following pKB values: pFHHSiD (8.7), pirenzepine (7.5) and AFDX 116 (6.2). 5. In the presence of the endothelium, low concentrations of pirenzepine (10(-9)-10(-7) M) produced leftward shifts of the ACh concentration-response curves. This potentiating effect of pirenzepine was reversed by endothelial cell removal. In preparations precontracted with the thromboxane-mimetic, U46619, the putative M1-selective agonist, McN-A-343, induced a biphasic relaxation with log IC50 of 8.53 +/- 0.14 and 5.02 +/- 0.08 for the first and second phase of the relaxation, respectively, and maximal relaxations of 22.8 +/- 4.3% and 41.1 +/- 5.4% (n = 16). McN-A-343 relaxed the vessels in the presence of 10(-7) M pFHHSiD and 3 x 10(-7) M AFDX 116, but not after incubation with 10(-9) M pirenzepine. 6. It is concluded from the pKB values for the antagonists used, that contraction induced by ACh in lamb coronary resistance arteries, in either the presence or the absence of the endothelium, is mediated via the M3 subtype of muscarinic receptors, while muscarinic receptors of another subtype at the endothelium seem to modulate the contractile response to ACh.

Acetylcholine↗

PubMed1993

Different muscarinic receptor subtypes mediating the phasic activity and basal tone of pig isolated intravesical ureter.

1. We have studied the effects of muscarinic cholinoceptor agonists and specific antagonists on both phasic activity and basal tone of the isolated intravesical ureter of the pig by means of isometric techniques in vitro. 2. Acetylcholine in the presence and absence of physostigmine increased both phasic activity and basal tone of ureteral strips in a concentration-dependent manner. Moreover carbachol, methacholine and oxotremorine-M increased both contractile parameters while bethanechol and McN-A-343 evoked only increases in tone without affecting the frequency of the phasic contractions. 3. The nicotinic receptor blocker, hexamethonium (10(-6)-10(-4) M), failed to modify the contractions evoked by a single dose of carbachol (10(-5) M), whilst the muscarinic antagonist, atropine inhibited both phasic and tonic responses. 4. The muscarinic M1 (pirenzepine), M2 (AF-DX 116 and methoctramine), M3 (4-DAMP, HHSiD and p-F-HHSiD), and putative M4 receptor (tropicamide) antagonists significantly reversed increases in both frequency of phasic activity and baseline tone induced by a submaximal dose of carbachol (10(-5) M). The pIC50 values for inhibition of the induced phasic activity were: atropine (10.16) > 4-DAMP (9.12) > HHSiD (8.22) = methoctramine (7.98) = p-F-HHSiD (7.88 > tropicamide (7.62) = pirenzepine (7.53) = AF-DX 116 (7.45) and for inhibition of basal tone were: atropine (10.73) > 4-DAMP (9.32) > HHSiD (8.65) = pirenzepine (8.43) = p-F-HHSiD (8.38) > methoctramine (7.79) > tropicamide (7.53) > AF-DX 116 (7.04). 5. The antagonist profile indicates that an M1 receptor mediates the tonic response while the phasic activity could involve either both M2 and M3 or an M4 muscarinic receptor. These results suggest that different muscarinic receptor subtypes mediate the phasic and tonic contractile activity induced by a submaximal concentration of carbachol in the porcine intravesical ureter.

Animals↗

PubMed1992

Mediation of contraction and relaxation by alpha- and beta-adrenoceptors in the ureterovesical junction of the sheep.

The effects of alpha- and beta-adrenoceptor agonists and antagonists were studied in the sheep ureterovesical junction. Non-specific adrenergic agonists such as adrenaline and noradrenaline induced contraction in the sheep ureterovesical junction, suggesting a predominance of alpha-over beta-adrenoceptors in this functional unity. An inhibition of the noradrenaline-induced contraction was observed after prior blocking with prazosin (10(-7) M) and yohimbine (10(-7) M), the effect of prazosin being more potent than that of yohimbine. The effect of phenylephrine on alpha 1-adrenoceptors was more potent than that of B-HT 920 on alpha 2-adrenoceptors. Isoproterenol caused a concentration-dependent relaxation that was inhibited by propranolol (10(-6) M), pafenolol (10(-5) M) and butoxamine (10(-5) M). These results suggest that ureterovesical junction contraction is mediated by both alpha 1 and alpha 2-adrenoceptors, alpha 1 predominating over alpha 2. Relaxation is mediated by beta-adrenoceptors of the beta 1 and beta 2 subtypes.

Adrenergic alpha-Agonists↗

PubMed1992

Mediation of contraction by cholinergic muscarinic receptors in the ureterovesical junction.

1. The muscarinic receptor profile of the sheep ureterovesical junction has been studied by means of in vitro techniques. The relative potency (pD2 = -log EC50) and maximum effect (Emax) observed with carbachol were 51-fold and 25% greater than with acetylcholine respectively. This could be due to the presence of active acetylcholinesterase in this tissue. 2. The pA2 values obtained with the muscarinic antagonists were pirenzepine (8.52), AF-DX 116 (8.05), 4-DAMP (9.41) and hexahydroxiladifenidol (8.66). The slope values of Schild plots were not significantly different from unity, indicating competitive antagonism. Furthermore, when the slopes were constrained to 1, no significant differences were found between the pA2 values. These pA2 values were similar to those observed in other mammalian smooth muscles. 3. It is concluded that muscarinic receptors in the sheep ureterovesical junction smooth muscle belong to the M1, M2 and M3 subtypes and mediate contraction of the ureterovesical junction, which suggests that during parasympathetic stimulation they might prevent vesicoureteral reflux.

Animals↗

PubMed1992

Noradrenaline modulates smooth muscle activity of the isolated intravesical ureter of the pig through different types of adrenoceptors.

1. We have studied the effects of alpha- and beta-adrenoceptor agonists and antagonists on both phasic peristaltic activity and basal tone of the isolated intravesical ureter of the pig by means of isometric techniques in vitro. 2. Spontaneous phasic activity was exhibited by 21% of pig intravesical ureter preparations manifested as rhythmic contractions with average frequency and amplitude of 2.54 +/- 0.18 min-1 and 1.48 +/- 0.16 g (n = 31), respectively. 3. Adrenaline, noradrenaline and phenylephrine induced concentration-dependent increases in both phasic activity and basal tone of ureteral preparations, all three agonists being more potent in modifying ureteral phasic activity than baseline tone. B-HT 920, B-HT 933 and clonidine had no significant effect. 4. Phentolamine (10(-9)-10(-7) M) and prazosin (3 x 10(-11)-3 x 10(-8) M) significantly inhibited increases in both frequency of phasic activity and baseline tone induced by a submaximal dose of noradrenaline. Rauwolscine (10(-9)-10(-7) M) affected only the tone evoked by noradrenaline and higher concentrations of this antagonist were needed to block phasic activity. 5. Pretreatment of ureteral strips with the beta-adrenoceptor antagonist, propranolol (10(-6) M), significantly increased the maximum contraction evoked by noradrenaline. After incubation with phentolamine (10(-6) M), noradrenaline (10(-7)-10(-6) M) decreased phasic activity induced by prostaglandin F2 alpha (10(-5) M). Isoprenaline and salbutamol also abolished PGF2 alpha-induced phasic activity. Pafenolol (10(-6) M) and butoxamine (10(-6) M) blocked the inhibitory effect of noradrenaline, isoprenaline, and salbutamol on PGF2 alpha-induced phasic activity. 6. These results suggest that noradrenaline may modulate both phasic peristaltic activity and basal tone of pig intravesical ureter through both alpha- and beta-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMed1992

Effect of induced hypercholesterolemia in rabbits on functional responses of isolated large proximal and small distal coronary arteries.

We studied the effects of hypercholesterolemia on the vascular responses of proximal and distal parts of the rabbit coronary circulation in two consecutive studies. For 12 weeks, New Zealand White rabbits were fed a control diet or a diet with 1% cholesterol dissolved in either 3% coconut oil (study A) or ether (study B). Isolated proximal epicardial and distal intramyocardial coronary arteries from control and hypercholesterolemic rabbits were mounted for isometric tension recording in a double myograph. In study A for hypercholesterolemic rabbits (n = 12), the maximal relaxation and sensitivity to acetylcholine (ACh) were significantly decreased in proximal coronary segments contracted with 30 mmol/l potassium solution compared with segments from control rabbits (n = 13). The only change observed in distal coronary segments was a slight decrease in relaxation in response to low ACh concentrations (10(-8) and 3 x 10(-8) mol/l). However, in study B for proximal coronary and distal coronary segments from hypercholesterolemic rabbits (n = 13), the area under the ACh relaxation curve was increased compared with that of control rabbits (n = 12). Other parameters that were similarly affected in studies A and B include the following: 1) proximal coronary segments from hypercholesterolemic rabbits were more sensitive to sodium nitroprusside (SNP) than were those from control rabbits, but this was not true for distal coronary segments; 2) endothelial removal from arterial segments of control rabbits induced a significant increase in sensitivity and maximal relaxation to SNP of proximal coronary and distal coronary arteries; 3) in segments from hypercholesterolemic rabbits, the absence of endothelium did not alter the response of proximal coronary segments to SNP but did augment the relaxation of distal coronary segments to SNP; 4) the maximal response to 5-hydroxytryptamine in proximal coronary arteries from hypercholesterolemic rabbits was increased compared with those from control rabbits, whereas such changes were not observed in distal coronary arteries; and 5) histological examination showed the presence of atheromatous plaques in proximal coronary but not in distal coronary segments from treated animals. In conclusion, the present investigation demonstrates that induced hypercholesterolemia alters both the structure and function of proximal parts of the coronary circulation. In distal coronary arteries of hypercholesterolemic rabbits, the only change observed was an impaired endothelium-dependent cholinergic relaxation, but even this change appeared to be dependent on the manner in which cholesterol was added to the diet, although parallel studies are required to confirm this.

Acetylcholine↗

PubMed1991

Distribution and function of cholinergic receptors in the sheep detrusor muscle.

The distribution of cholinergic nerve fibres, as well as the characterization of the muscarinic receptors responsible for the contraction, were determined in the detrusor smooth muscle of the sheep. The results obtained demonstrated a rich presence of acetylcholinesterase (AChE)-positive fibres distributed throughout the bladder body forming dense neuromuscular, subepithelial and perivascular plexuses. Furthermore, intramural ganglia containing AChE-positive cell bodies were identified. However, acetylcholine and carbachol induced a dose-dependent contraction of detrusor smooth muscle. The effect observed with carbachol was competitively antagonized by atropine (pA2: 8.94), pirenzepine (pA2: 7.38), AF-DX 116 (pA2: 7.35), 4-DAMP (pA2: 9.26) and hexahydroxiladifenidol (HHSiD) (pA2: 8.49). The pA2 value for pirenzepine is intermediate between M1- and M2-receptors which suggests that this antagonist does not act on M1- or M2-receptors, but that it does on M3-receptors. The pA2 value for AF-DX 116 is consistent with the presence of M2-receptors in this tissue. Moreover, the pA2 values obtained for both 4-DAMP and HHSiD are in agreement with the presence of M3-receptors, due to the lack of effect of pirenzepine on M1-muscarinic receptors. These results indicate the existence of a rich parasympathetic innervation in the sheep detrusor muscle and suggest that its contraction could be mediated by the stimulation of muscarinic receptors belonging to both M3- and M2-subtypes.

Acetylcholine↗

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

Alpha- and beta-adrenoceptors in the sheep urinary bladder.

A study was undertaken to determine the presence and distribution of alpha- and beta-adrenoceptors in the sheep bladder body and base. In the bladder body, noradrenaline and isoproterenol induced relaxation which was significantly inhibited by propranolol, pafenolol and butoxamine. In the presence of propranolol (10(-5) M), noradrenaline induced a small contraction, as well as phenylephrine, but B-HT 920 failed to cause any effect on the bladder body. In the bladder base, noradrenaline caused a contraction that was significantly inhibited by prazosin but not by yohimbine. Phenylephrine also induced a contractile response in this structure which was inhibited by prazosin. Isoproterenol caused a relaxation that was significantly inhibited by propranolol and pafenolol but not by butoxamine. Relaxation was mediated by both beta 1 and beta 2-adrenoceptors in the detrusor muscle and by beta 1-adrenoceptors in the bladder base. Alpha 1-adrenoceptors contributed to maintain the detrusor tone and contract the bladder base.

Adrenergic beta-Antagonists↗

PubMed1991

Mechanisms implicated in the histamine response of the sheep ureterovesical junction.

The isotonic response of the sheep ureterovesical junction to histamine receptor agonists and antagonists was studied in vitro. Histamine (10(-7)-10(-4) M) produced a concentration-dependent contraction which was dependent on the extracellular calcium concentrations. Nifedipine (10(-9)-10(-6) M) partially inhibited the contractile response to histamine. 2-Methylhistamine and 2-pyridylethylamine elicited contractile effect in a concentration-related manner. The order of potency was histamine greater than 2-methylhistamine greater than 2-pyridylethylamine. Dimaprit and 4-methylhistamine produced no response in this tissue. The histamine contraction was antagonized by mepyramine, the pA2 value being 8.41, but not by cimetidine (10(-4) M). Scopolamine (10(-5) M) and indomethacin (10(-6) M) had an inhibitory effect. Phentolamine (10(-5) M), propranolol (10(-7)) and hexamethonium (10(-6) M) did not alter the histamine-induced contractions. The present results indicate that the response to histamine in sheep ureterovesical junction is mediated mainly by a direct action on the smooth muscle through excitatory histamine H1-receptors and partly by an indirect action via the stimulation of intramural cholinergic nerves.

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

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↗