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S P Duckles

Publications and source records attributed to S P Duckles.

At least 19 recordsLinked to original sources
PubMed1999

Gender difference in levels of alpha2-adrenoceptor mRNA in the rat tail artery.

To investigate the hypothesis that differing mRNA levels underlie gender differences in the contractile response of the rat tail artery, alpha2-adrenoceptor mRNA was measured using in situ hybridization. Messenger RNA for the alpha2A- and alpha2C-adrenoceptor subtypes was found localized to the smooth muscle layer. There was no detectable mRNA present for the alpha2B-adrenoceptor subtype. Levels of alpha2C-adrenoceptor mRNA were greater in female compared to male tail arteries (417 +/- 35 vs. 263 +/- 38 dpm/mg, P = 0.01), while levels of alpha2A-adrenoceptor mRNA were the same in both sexes. Levels of alpha2-adrenoceptor mRNA may parallel levels of functioning protein present in the rat tail artery.

Animals↗
PubMed1999

Impact of development and chronic hypoxia on NE release from adrenergic nerves in sheep arteries.

To examine effects of development and chronic high-altitude hypoxia on sympathetic nerve function in sheep, norepinephrine release was measured in vitro from middle cerebral and facial arteries. Capsaicin was used to test the role of capsaicin-sensitive sensory nerves; norepinephrine release was not altered by capsaicin treatment. Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, decreased stimulation-evoked norepinephrine release in middle cerebral arteries from normoxic sheep with no effect in hypoxic arteries or facial arteries. Thus NO-releasing nerves augmented norepinephrine release. Furthermore, the function of NO-releasing nerves declined after chronic hypoxia. Despite loss of the augmenting effects of NO, stimulation-evoked fractional norepinephrine release was unchanged after chronic hypoxia, suggesting that middle cerebral arteries adapt to hypoxia by increasing stimulation-evoked norepinephrine release. In fetal facial arteries, chronic hypoxia resulted in a decline in stimulation-evoked norepinephrine release, but there was an increase in the adult facial artery. In the adult, adaptation to chronic hypoxia is similar in both cerebral and facial arteries. However, differential adaptation in fetal adrenergic nerves may reflect differences in fetal redistribution of blood flow in the face of chronic hypoxia but could also possibly contribute to increased incidence of fetal morbidity.

Adrenergic Fibers↗
PubMed1998

Melatonin mediates two distinct responses in vascular smooth muscle.

The pineal hormone melatonin was found to produce two distinct contractile responses in vascular smooth muscle. In isolated rat caudal artery segments, denuded of endothelium, melatonin (10(-10)-10(-7) M) potentiated phenylephrine-induced contractions in a concentration-dependent manner. At higher melatonin concentrations (10(-7)-10(-5) M), however, the potentiating effect was attenuated. In the presence of the melatonin MT2 receptor antagonist, 4-phenyl-2-acetamidotetraline (4P-ADOT), the attenuated constrictor responses were selectively enhanced. These results are consistent with the hypothesis that melatonin activates two receptor subtypes in vascular smooth muscle; MT2 receptors may induce relaxation, while a second receptor subtype mediates vasoconstriction.

Adrenergic alpha-Agonists↗
PubMed1998

Effect of melatonin in the rat tail artery: role of K+ channels and endothelial factors.

1. The role of endothelial factors and potassium channels in the action of the pineal hormone melatonin to potentiate vasoconstrictor responses was investigated in the isolated perfused tail artery of the rat. 2. Melatonin (100 nM) potentiated contractile responses to both adrenergic nerve stimulation and alpha1-adrenoceptor stimulation by phenylephrine. After removal of the endothelium, melatonin no longer caused potentiation. 3. The potentiating effect of melatonin was also lost when nitric oxide synthase was inhibited with L-NAME (10 nM). Thus potentiating effects depend on the presence of nitric oxide released by the endothelium. However, melatonin did not affect relaxation responses to acetylcholine in endothelium-intact arteries, nor did melatonin modulate relaxing responses to sodium nitroprusside in endothelium-denuded arteries. While melatonin does not appear to modulate agonist-induced release of nitric oxide nor its effect, melatonin may modulate nitric oxide production induced by flow and shear stress. 4. When the Ca2+-activated K+ channel opener, NS 1619 (10 microM), was present, potentiating effects of melatonin were restored in endothelium-denuded vessels. However, addition of the opener of ATP-sensitive K+ channels, cromakalim (3 microM), did not have the same restorative effect. Furthermore, addition of a blocker of Ca2+-activated K+ channels, tetraethylammonium (1 mM), significantly attenuated potentiating effects of melatonin. These findings support the hypothesis that melatonin inhibits the activity of large conductance Ca2+-activated K+ channels to produce its potentiating effects. 5. Thus in the rat perfused tail artery, potentiation of constriction by melatonin depends on the activity of both endothelial factors and Ca2+-activated K+ channels. Our findings suggest that melatonin inhibits endothelial K+ channels to decrease flow-induced release of nitric oxide as well as block smooth muscle K+ channels to enhance vascular tone.

Acetylcholine↗
PubMed1998

Estrogen reduces myogenic tone through a nitric oxide-dependent mechanism in rat cerebral arteries.

Gender differences in the incidence of stroke and migraine appear to be related to circulating levels of estrogen; however, the underlying mechanisms are not yet understood. Using resistance-sized arteries pressurized in vitro, we have found that myogenic tone of rat cerebral arteries differs between males and females. This difference appears to result from estrogen enhancement of endothelial nitric oxide (NO) production. Luminal diameter was measured in middle cerebral artery segments from males and from females that were either untreated, ovariectomized (Ovx), or ovariectomized with estrogen replacement (Ovx + Est). The maximal passive diameters (0 Ca2+ + 1 mM EDTA) of arteries from all four groups were identical. In response to a series of 10-mmHg step increases in transmural pressure (20-80 mmHg), myogenic tone was greater and vascular distensibility less in arteries from males and Ovx females compared with arteries from either untreated or Ovx + Est females. In the presence of NG-nitro-L-arginine methyl ester (L-NAME; 1 microM), an NO synthase inhibitor, myogenic tone was increased in all arteries, but the differences among arteries from the various groups were abolished. Addition of L-arginine (1 mM) in the presence of L-NAME restored the differences in myogenic tone, suggesting that estrogen works through an NO-dependent mechanism in cerebral arteries. To determine the target of NO-dependent modulation of myogenic tone, we used tetraethylammonium (TEA; 1 mM) to inhibit large-conductance, calcium-activated K+ (BKCa) channels. In the presence of TEA, the myogenic tone of arteries from all groups increased significantly; however, myogenic tone in arteries from males and Ovx females remained significantly greater than in arteries from either untreated or Ovx + Est females. This suggests that activity of BKCa channels influences myogenic tone but does not directly mediate the effects of estrogen. Estrogen appears to alter myogenic tone by increasing cerebrovascular NO production and/or action.

Animals↗
PubMed1998

Effect of simulated microgravity on vascular contractility.

Microgravity was simulated in Sprague-Dawley (SD) and Wistar (W) rats by using a tail harness to elevate the hindquarters, producing hindlimb unweighting (HU). After 20 days of HU treatment, blood vessels from both HU and control rats were cut into 3-mm rings and mounted in tissue baths for the measurement of isometric contraction. HU treatment decreased the contractile response to 68 mM K+ in abdominal aorta from W rats. HU treatment also decreased the contraction to 68 mM K+ in carotid arteries from both rat strains and in femoral arteries from W but not SD rats. HU treatment reduced the maximal response to norepinephrine in all arteries except the femoral from SD rats. HU treatment reduced the maximal response of jugular vein from W rats to 68 mM K+ but had no effect on that response in femoral vein from either rat strain. HU treatment also had no significant effect on the maximal response to norepinephrine in veins. These results demonstrate that HU treatment caused a nearly universal reduction of contractility in arteries, but generally had no effect in veins.

Animals↗
PubMed1998

Simulated microgravity increases myogenic tone in rat cerebral arteries.

Adaptation of the cerebral circulation to microgravity was investigated in rat middle cerebral arteries after 20 days of hindlimb unweighting (HU). Myogenic responses were measured in isolated, pressurized arteries from HU and control animals. Maximal passive lumen diameters, obtained in the absence of extracellular Ca2+ plus EDTA, were not significantly different between groups (249 vs. 258 micrometer). In physiological salt solution, arteries from both HU and control animals maintained a constant lumen diameter when subjected to incremental increases in transmural pressure (20-80 mmHg). However, the diameter of arteries from HU animals was significantly smaller than that of arteries from control animals at all pressures; this difference could be eliminated by exposure to the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. After HU treatment, transient distensibility of the artery wall in response to pressure was also significantly decreased, whereas the frequency and amplitude of vasomotion were increased. The latter changes were not affected by NG-nitro-L-arginine methyl ester. Thus simulated microgravity increases cerebral artery myogenic tone through both nitric oxide synthase-dependent and -independent mechanisms.

Animals↗
PubMed1997

Neuropeptide Y Y1 receptor blockade does not alter adrenergic nerve responses of the rat tail artery.

Using the selective neuropeptide Y Y1 receptor antagonist, BIBP3226 [(N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-argininamide], the role of endogenous neuropeptide Y in mediating vasoconstrictor responses to adrenergic nerve stimulation was investigated by recording isometric force from isolated rat tail artery segments. BIBP3226 had no effect on contractile responses to adrenergic nerve stimulation (10 pulses; 0.5-2 Hz), but it completely blocked the enhancement of contraction produced by exogenous neuropeptide Y. When frequency and train length of the transmural nerve stimulation were increased (100 pulses; 1-16 Hz), contractile responses were still unaffected by BIBP3226. A peptidase inhibitor mixture known to increase responses to exogenous neuropeptide Y was added; however, BIBP3226 still did not influence contractile responses to adrenergic nerve stimulation. Thus, contractile responses to adrenergic nerve stimulation in the rat tail artery do not appear to involve the release and postjunctional action of endogenous neuropeptide Y; however, exogenous neuropeptide Y does potentiate these responses by acting on Y1 receptors.

Animals↗
PubMed1997

Vascular responses to neuropeptide Y are greater in female than male rats.

Sex differences in vascular effects of neuropeptide Y (NPY) were investigated in isolated tail artery ring segments from male and female F344 rats. Both pre- and postjunctional effects of NPY appeared to be greater in females. NPY potentiated contractions elicited by transmural adrenergic nerve stimulation (TNS), consistent with an effect on smooth muscle Y1 receptors. The degree of potentiation was significantly greater in arteries from females than males. Ovariectomy of the females resulted in a decrease in potentiation, while orchiectomy of the males resulted in an enhanced NPY effect. When NPY potentiation was measured in the presence of peptidase inhibitors, the effect of exogenous NPY was enhanced; however the enhancement was greater in arteries from females than either males or ovariectomized females. Possible male-female differences in inhibitory prejunctional Y2 receptor function were addressed using the selective agonist NPY13-36. At a low frequency of stimulation (0.5 Hz), NPY13-36 inhibited the response to TNS in arteries from females and castrated males; however, NPY13-36 had no significant effect on responses to TNS in arteries from males or ovariectomized females. Thus gonadal hormones appear to modulate several components involved in NPY neurotransmission, including tissue peptidase activity, postjunctional Y1 and prejunctional Y2 receptors. These effects may contribute to significant differences observed in vascular reactivity between females and males.

Animals↗
PubMed1997

Noradrenaline content and release in male and female rat tail arteries.

In tail-artery segments isolated from male and female control and gonadectomized rats, noradrenaline content and noradrenaline released by electrical stimulation were measured by high-pressure liquid chromatography. Noradrenaline content, expressed as a function of tissue wet weight, was higher in tail arteries from female than from male rats, but there were no significant differences between control and orchiectomized males or control and ovariectomized females. Electrical stimulation of vascular segments in the presence of cocaine (10(-5) M) and deoxycorticosterone (10(-5) M) induced release of noradrenaline that was increased in the presence of the alpha 2-adrenergic antagonist idaxozan (10(-6) M). However, no differences were found in either basal or stimulation-evoked fractional noradrenaline release between male or female, control or gonadectomized animals. These results indicate that control of noradrenaline release at the nerve ending does not appear to be different between genders. There may be differences in adrenergic density, but noradrenaline content does not appear to be modified by circulating gonadal hormones.

Adrenergic alpha-Antagonists↗
PubMed1997

Ovariectomy eliminates sex differences in rat tail artery response to adrenergic nerve stimulation.

The influence of gonadal hormones on vasoconstrictor responses to adrenergic nerve stimulation was investigated by comparing tail arteries from intact and gonadectomized male and female Fisher 344 rats. Arterial ring segments from females were significantly less responsive to transmural nerve stimulation (1-8 Hz) than arteries from age-matched males. Significant male-female differences persisted after correcting the contractile responses for sex-related differences in arterial mass, optimal resting tension, and maximal contractile force. Arteries were taken from cycling, intact females in either proestrus, estrus, metestrus, or diestrus, but no significant differences were found among the four stages for vasoconstrictor responses to either adrenergic nerve stimulation or exogenous norepinephrine. These data suggest adrenergic function in the artery is not affected by hormonal variations during the estrous cycle. After bilateral ovariectomy, however, contractile responses of female arteries to adrenergic nerve stimulation were increased to levels similar to those observed in male arteries. Orchidectomy of males, in contrast, had no effect on neural-evoked contraction. Low concentrations of norepinephrine also produced greater contractile responses in male compared with female arteries; however, this sex-related difference was eliminated by orchidectomy but not ovariectomy. Taken together, the results indicate that circulating gonadal hormones contribute to gender differences observed in rat tail artery. Vasoconstrictor responses to exogenous norepinephrine appear to be enhanced by testicular hormones. In contrast, vasoconstriction induced by adrenergic nerve stimulation appears to be influenced by chronic exposure to circulating ovarian hormones, resulting in a smaller vascular response in female arteries.

Animals↗
PubMed1997

Melatonin directly constricts rat cerebral arteries through modulation of potassium channels.

The pineal hormone melatonin was found to decrease luminal diameter of rat middle cerebral artery segments, pressurized in vitro, in a concentration-dependent manner (concentration that produced a half-maximal effect = 2.7 nM). Contractile responses to melatonin were inhibited by luzindole, a melatonin receptor antagonist, but not by the serotonin receptor antagonist ketanserin. Pertussis toxin abolished the effect of melatonin, which is consistent with involvement of Gi or G(o) protein-coupled receptors. The maximal effect of melatonin was increased by elevating transmural pressure. When compared at the same pressure, contractions elicited by melatonin were smaller than those elicited by serotonin but similar in magnitude to those produced by tetraethylammonium or charybdotoxin, blockers of Ca(2+)-dependent, large-conductance K+ (BKCa) channels. The effect of melatonin was significantly attenuated in the presence of BKCa channel blockers, but not by apamin, a blocker of Ca(2+)-dependent, small-conductance K+ channels. Melatonin, like tetraethylammonium, significantly reduced vasodilation produced by NS-1619, an opener of BKCa channels. Contractile responses to melatonin were diminished in the presence of elevated extracellular K+ (16 mM), but they were not significantly affected by NG-nitro-L-arginine methyl ester. The results suggest that activation of melatonin receptors on rat cerebral arteries increases vascular tone through Gi or G(o) protein-mediated inhibition of BKCa channels. Thus melatonin, which is secreted during the night, can directly influence the contractile state of cerebral arteries.

Animals↗
PubMed1996

Sex differences in the effects of 17 beta-estradiol on vascular adrenergic responses.

The in vitro effects of 17 beta-estradiol on vascular responses to adrenergic nerve stimulation were studied in perfused tail arteries from age-matched male and female rats. Nerve stimulation resulted in vasoconstriction that was greater in male arteries. Addition of 17 beta-estradiol (3 x 10(-5) M) reduced the vasoconstrictor responses in both male and female arteries, but the reduction was significantly greater in the females. Gonadectomy of the animals for 1 month prior to the experiment did not alter the in vitro responses to 17 beta-estradiol in either males or females. 17 beta-Estradiol (10(-6) - 3 x 10(-5) M) also relaxed perfused tail arteries precontracted with KCl (50 mM); however the relaxation was not different between males and females, either intact or gonadectomized. Stimulation-evoked release of noradrenaline from adrenergic nerves of perfused tail arteries was measured, but no differences were found between males and females, nor was release modified by in vitro exposure to 17 beta-estradiol (10(-5) M). These results suggest that 17 beta-estradiol acts directly on postjunctional mechanisms to relax tail arteries of either sex. The effect of the hormone on arteries constricted by adrenergic nerve stimulation, however, is greater in females compared to males.

Animals↗
PubMed1996

Relaxant effects of 17 beta-estradiol in the rat tail artery are greater in females than males.

To investigate whether sex differences contribute to the variability reported for acute effects of 17 beta-estradiol on vascular reactivity, the response to 17 beta-estradiol was compared in male and female isolated perfused rat tail arteries. 17 beta-Estradiol (10(-7)-10(-5) M) attenuated the contractile response to norepinephrine in female, but not male, arteries, but had no effect when the endothelium was removed. Relaxation to 17 beta-estradiol reached a steady state within approximately 15 min. This hormone appears to acutely relax pre-contracted arteries from females but not males by a non-genomic effect requiring an intact endothelium.

Animals↗
PubMed1996

Evidence for decline in intracellular calcium buffering in adrenergic nerves of aged rats.

Age-related alterations in neuronal intracellular calcium regulation and neurotransmitter release have been widely reported. We have investigated the impact of age on neurotransmitter release and intracellular calcium buffering in adrenergic nerve endings of the isolated rat tail artery and on intracellular calcium in acutely dissociated cells from the superior cervical ganglion. Advancing age, from 6 to 27 months, resulted in significantly increased stimulation-evoked norepinephrine release from the isolated rat tail artery, an effect which persisted when neuronal and extraneuronal uptake were blocked with cocaine and deoxycorticosterone and presynaptic alpha adrenergic receptors were blocked with idazoxan. Alterations in extracellular calcium had significant effects on stimulation-evoked norepinephrine release, but these were much more marked in old, compared to young, arteries. Blockade of mitochondrial calcium accumulation with dinitrophenol had no significant effect on stimulation-evoked norepinephrine release from 6-month-old arteries, but in 20-month-old arteries, treatment with dinitrophenol resulted in a substantial increase in stimulation-evoked norepinephrine release. However, when extracellular calcium was increased to 5 mM in 6 month-old-arteries, then addition of dinitrophenol resulted in an increase in stimulation-evoked norepinephrine release. Measurement of intracellular calcium in acutely dissociated superior cervical ganglion cells using fura-2 revealed substantial age-related differences. Peak calcium transients in 20-month-old ganglion cells depolarized with 68 mM K+ were substantially higher than in 6-month-old cells. Together these findings support the hypothesis that in adrenergic nerves advancing age results in a disruption of intracellular calcium buffering leading to higher levels of intracellular calcium and increased transmitter release.

2,4-Dinitrophenol↗
PubMed1996

Effects of gonadal steroids on vascular function.

Estrogen and other sex steroid hormones can affect multiple functions of the vascular wall including production and activity of endothelium-derived factors, expression of adhesion molecules, contraction of the smooth muscle to adrenergic nerve stimulation and smooth muscle proliferation and migration. Effects on response of the smooth muscle may be associated with regulation of surface receptors, second messenger systems and contractile protein isoforms. Sex steroid hormones may act synergistically with other hormones to modulate vascular reactivity across the normal ovarian cycle and during pregnancy. Estrogen may also affect remodeling of the vascular wall through inhibition of smooth muscle cell proliferation, stimulation of cell migration and secretion of matrix proteins. It is becoming apparent that modulation of vascular function by sex steroid hormones involves complex interactions. Not all actions of estrogen can be explained by genomic regulation of protein synthesis. Continued progress in understanding how hormones modulate vascular function will depend, in part, on clearer interpretation of data relative to the particular conditions of each experiment. Important aspects to be considered include the effect of gender and vessel type on the distribution and function of hormone receptors present in the vessel wall; use of hormones within physiological concentration ranges; and more precise determination of the influence of hormone treatment duration whether acute, subacute or chronic.

Animals↗
PubMed1995

Melatonin receptors mediate potentiation of contractile responses to adrenergic nerve stimulation in rat caudal artery.

The hormone melatonin potentiated contractile responses to adrenergic nerve stimulation in isolated ring segments of rat caudal artery. This effect was inhibited by the melatonin receptor antagonist luzindole but not by the serotonin 5-HT2 receptor antagonist ketanserin. Melatonin had no direct effects on vascular tone. Melatonin agonists potentiated contractile responses with a relative order of potency (2-iodomelatonin, EC50 = 0.6 nM; melatonin, EC50 = 4.7 nM; N-acetylserotonin, EC50 = 1.5 microM) that is consistent with the melatonin ML1 receptor subtype. Melatonin also potentiated contractions elicited by exogenous norepinephrine and produced its effects in the absence of an intact endothelium. These data suggest that melatonin acts on receptors in the smooth muscle. The caudal artery provides a useful functional assay for pharmacological analysis of melatonin receptors. Physiologically, melatonin may activate its receptors at night to influence thermoregulation in the rat by enhancing the effects of sympathetic input to the caudal artery.

Animals↗