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At least 649 records · Page 36Linked to original sources

PubMed1981

Comparison of two alpha-noradrenergic agonists (clonidine and guanfacine) on norepinephrine turnover in the cortex of rats during morphine abstinence.

The effects of the alpha-agonists clonidine and guanfacine on rat cortical norepinephrine turnover during morphine withdrawal were assessed. Cortical norepinephrine levels were measured, after administration of alpha-methyl-p-tyrosine, by fluorometric assay. Chronic treatment with morphine did not affect norepinephrine levels or norepinephrine turnover. In control animals, doses up to 200 micrograms/kg clonidine and 1060 micrograms/kg guanfacine did not affect norepinephrine steady state levels, but did reduce alpha-methyl-p-tyrosine-induced norepinephrine depletion. As little as 5 micrograms/kg clonidine reversed the accelerated turnover observed during naloxone precipitated morphine withdrawal; while for guanfacine, the minimum effective dose was 212 micrograms/kg. the ED50 for guanfacine's reversal of the withdrawal-induced acceleration of turnover was approximately 60 times that for clonidine.

Adrenergic alpha-Agonists↗

PubMed1984

Activation mechanisms of human renal artery: effects of KCl, norepinephrine and nitrendipine upon tension development and 45Ca influx.

The activation of human vascular smooth muscle by KCl-induced depolarization or norepinephrine and the inhibition produced by nitrendipine were studied in the isolated human renal artery. The contractile response of arterial rings to 80 mM KCl was abolished when extracellular Ca2+ was removed, and was inhibited by nitrendipine (IC50 = 10(-8) M). In contrast, a residual, transient contractile response to norepinephrine remained when extracellular Ca2+ was removed and the norepinephrine-induced contractions obtained in the presence of extracellular Ca2+ were not blocked by nitrendipine. KCl caused a stimulation of 45Ca influx which was completely prevented by 10(-6) M nitrendipine. Norepinephrine also caused a stimulation of 45Ca influx; however, the norepinephrine-induced 45Ca influx was not prevented by 10(-6) M nitrendipine. These findings are consistent with the concept that depolarization-induced activation of the human renal artery is primarily dependent upon a stimulation of Ca2+ influx; whereas activation by norepinephrine involves the release of intracellular Ca2+ in addition to the activation of a separate, receptor-operated Ca2+ influx pathway.

Biological Transport↗

PubMed1987

Adenosine diphosphate potentiates the inhibition of norepinephrine-induced relaxation by 5-hydroxytryptamine in canine coronary arteries.

Vasoactive substances released from aggregating platelets inhibit beta-adrenergic neurotransmission in coronary arteries. Studies were carried out on the effects of two such vasoactive substances on canine coronary arteries, at concentrations equivalent to that released by platelets under physiological conditions. 5-Hydroxytryptamine (5 X 10(-7) M) reduced the sensitivity of coronary artery ring segments to the beta-adrenergic relaxing effects of norepinephrine. Adenosine diphosphate (3 X 10(-6) M) further reduced the sensitivity to norepinephrine caused by 5-hydroxytryptamine, while the nucleotide alone had no significant effect. 5-Hydroxytryptamine and adenosine diphosphate acted selectively on the norepinephrine-induced relaxation; whereas the relaxatory response of the vessel to nitroprusside, a direct muscle relaxant, was unaffected. 5-Hydroxytryptamine caused contraction of the tissue, but this opposing response did not account for the inhibition of the norepinephrine-induced relaxation observed in the presence of the indoleamine. The decreases in sensitivity to norepinephrine caused by 5-hydroxytryptamine and adenosine diphosphate were prevented by the serotonin receptor antagonist, methiothepin. The potentiation by adenosine diphosphate of the 5-hydroxytryptamine-induced shift in the relaxation caused by norepinephrine was blocked by the purine receptor antagonist, 8-(p-sulfophenyl)-theophylline. Neither adenosine nor alpha,beta-methylene adenosine diphosphate potentiated the action of 5-hydroxytryptamine, suggesting that phosphate hydrolysis of the nucleotide is required for the action of adenosine diphosphate. These results suggest that adenosine diphosphate potentiates the inhibitory effect of 5-hydroxytryptamine on the beta-adrenergic response of coronary arteries exposed to vasoactive substances released from platelets.

5-Hydroxytryptophan↗

PubMed1991

The role of endogenous norepinephrine release in potassium-evoked vasoconstriction of the rat tail artery.

Potassium-containing solutions are often used to study the sequence of events leading from excitation to vasoconstriction. In densely innervated vessels, such as the rat tail artery, potassium-induced vasoconstriction may be mediated via smooth muscle depolarization and release of endogeneous norepinephrine. The relative contribution of these two mechanisms--a 'direct' depolarization of the vascular smooth muscle cell membrane, and an 'indirect' sympathomimetic action--to the vasoconstrictor response was studied in the present paper. Perfusion/superfusion of the rat tail artery in vitro with potassium-containing solutions had different effects depending on the concentration used. A change in potassium concentration from 4.7 to 20 mM had no effect on either perfusion pressure or norepinephrine overflow. From 30 to 70 mM, potassium produced increasing amounts of norepinephrine overflow. Experiments with phentolamine and reserpine showed that this norepinephrine overflow contributed for up to half of the vasoconstrictor response observed. A second norepinephrine-independent mechanism was also involved but the latter appeared to be incapable of producing sustained contraction. At concentrations of potassium above 50-70 mM, the results of experiments with (+/-)-propranolol suggest that the norepinephrine released by potassium has a beta-adrenoceptor-mediated vasorelaxant effect.

Animals↗

PubMed1993

Potentiation of dark onset feeding in obese mice (genotype ob/ob) following central injection of norepinephrine and clonidine.

Central monoaminergic neurotransmitters have been implicated in the control of food intake in different animal species but it remains unclear whether these same neurochemical systems effectively regulate feeding behaviour in the genetically obese (ob/ob) mouse. Neuropharmacological studies have demonstrated, for example, that microinjection of norepinephrine can elicit a reliable feeding response in the rat, particularly at dark onset. The present study was therefore designed to examine the impact of central injection of norepinephrine (20-160 nmol) and clonidine (5-80 nmol), an alpha 2-adrenoceptor agonist, on food intake in ob/ob mice and lean (+/?) controls. Presatiated obese and lean mice were injected with norepinephrine or clonidine immediately prior to the onset of the dark cycle. Food intake (kcal) was measured 1 h postinjection. Obese mice ingested more food than lean mice under baseline saline conditions. Injection of norepinephrine and clonidine increased eating in both phenotypes, although the ob/ob showed an enhanced feeding response to norepinephrine and clonidine administration. Intracerebroventricular pretreatment with the alpha 2-adrenoceptor antagonist yohimbine (12.5-50 nmol) significantly attenuated the increase in food intake observed in response to central injection of norepinephrine (40 nmol) and clonidine (10 nmol). However, the alpha 1-adrenoceptor antagonist corynanthine (15-60 nmol) or the beta-adrenoceptor antagonist propranolol (25-100 nmol) failed to alter noradrenergic feeding. These results suggest that modification of central alpha 2-noradrenergic function can alter natural feeding in mice, and that the ob/ob is particularly sensitive to this effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Cyclooxygenase inhibitors depress norepinephrine constriction of rat abdominal, but not thoracic, aorta.

Experiments were done on aortic rings (thoracic and abdominal) from young and retired breeder Lewis and Sprague-Dawley male rats. Constriction responses to norepinephrine, 5-hydroxytryptamine (5-HT), and prostaglandin F2 alpha, were done +/- the cyclooxygenase blockers, indomethacin or mefenamic acid. Indomethacin significantly depressed norepinephrine constriction in abdominal (but not thoracic) aorta of all groups. In additional studies of abdominal aorta from Lewis retired breeders, indomethacin and mefenamic acid depressed norepinephrine (but not 5-HT or prostaglandin F2 alpha) construction. Furthermore, indomethacin depressed norepinephrine constriction in vessels denuded of endothelial cells. The thromboxane receptor antagonist SQ 29548 did not alter norepinephrine constriction. Thus, in rat abdominal aorta, norepinephrine constriction is mediated by a constrictor prostanoid of vascular smooth muscle origin that is not thromboxane A2.

Adrenergic alpha-Antagonists↗

PubMed1996

Elevated myocardial interstitial norepinephrine concentration contributes to the regulation of Na+,K(+)-ATPase in heart failure.

Myocardial Na+,K(+)-ATPase is reduced in congestive heart failure. To study the regulation of Na+,K(+)-ATPase in congestive heart failure, we performed Western and Northern blot analyses of ventricular myocardium of dogs with pacing-induced congestive heart failure and chronic norepinephrine infusion, using isoform-specific antibodies and cDNA probes. Congestive heart failure and norepinephrine infusion caused similar increases in myocardial interstitial norepinephrine concentration and reductions of myocardial Na+,K(+)-ATPase alpha 3-subunit protein, but differed in their effects on myocardial Na+,K(+)-ATPase alpha 3-subunit gene expression. Chronic norepinephrine infusion produced no changes in the steady-state mRNA level for the alpha 3-subunit of Na+,K(+)-ATPase, suggesting that the changes in Na+,K(+)-ATPase protein were induced via a post-transcriptional mechanism. In contrast, down-regulation of the Na+,K(+)-ATPase alpha 3-subunit in the failing heart was accompanied by a decreased alpha 3-subunit mRNA level, indicating the presence of a transcriptional event. The alpha 1-subunit protein content and mRNA level were not affected by either norepinephrine infusion or rapid ventricular pacing. We conclude that, while elevated myocardial interstitial norepinephrine levels may contribute substantially to the down-regulation of the Na+,K(+)-ATPase alpha 3-subunit in the failing myocardium, additional regulatory factors are responsible for the decreased myocardial alpha 3-subunit mRNA expression in congestive heart failure.

Animals↗

PubMed1996

Norepinephrine attenuates serotonin inhibition of pial venous tone.

Serotonin (5-hydroxytryptamine, 5-HT) has been shown to inhibit the rhythmic constrictions, accompanied by an increase in cAMP synthesis, in porcine pial veins. Since porcine pial veins contain predominant postsynaptic alpha 2-adrenoceptors which are coupled to Gi-protein, the possibility that the inhibitory effect of 5-HT is antagonized by norepinephrine was examined pharmacologically, using tissue bath techniques. The results indicated that norepinephrine (0.1-1 microM) attenuated 5-HT-induced inhibition of rhythmic constriction. This effect of norepinephrine was mimicked by clonidine (an alpha 2-adrenoceptor agonist), but not by methoxamine (an alpha 1-adrenoceptor agonist). Furthermore, the effect of norepinephrine was prevented by yohimbine (an alpha 2-adrenoceptor antagonist) and pertussis toxin, but was not prevented by prazosin (an alpha 1-adrenoceptor antagonist). In parallel studies, the basal concentration of cAMP and that induced by 5-HT in the pial veins were inhibited by norepinephrine (0.3 microM). These results are consistent with the previous findings that 5-HT-induced inhibition of rhythmic constriction in the porcine pial veins is associated with an increase in vascular cAMP synthesis and suggest that norepinephrine attenuates 5-HT-induced inhibition of rhythmic constriction in part by negatively coupling to adenylate cyclase via alpha 2-adrenoceptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1985

Interaction of norepinephrine and superior cervical ganglion input in the rat pineal body.

The effects of superior cervical ganglion stimulation and the local application of norepinephrine or its antagonist propranolol were studied in 18 pineal cells. In 61% of the pineal cells, stimulation elicited excitation; the same cells also responded by excitation to norepinephrine ejection. When stimulation and norepinephrine ejection were applied together, summation (of the excitation) was observed in these cells. Several cells that failed to respond to stimulation did respond to norepinephrine ejection, but with the opposite pattern, i.e., decrease of firing rates. Propranolol prevented the norepinephrine-induced excitation and inhibition, as well as the excitation produced by stimulation. We suggest that norepinephrine regulates pineal activity by two routes: activation of the sympathetic neuronal input and inhibition by way of the circulation.

Animals↗

PubMed1983

Minireview. Presynaptic receptors and alterations in norepinephrine release in spontaneously hypertensive rats.

The ability of blood vessels to constrict to a given stimulus is significantly increased in spontaneously hypertensive rats (SHR). Such an increase in the vasoconstrictor responsiveness contributes to the elevated peripheral vascular resistance noted in SHR. The present review discusses evidence in support of the concept that an increased release of norepinephrine during sympathetic nerve stimulation may contribute to the increase in vasoconstrictor responsiveness and, subsequently, to an increase in vascular resistance in the SHR. Several studies suggest that the exocytotic release of norepinephrine from sympathetic nerves may be altered by endogenously occurring neurohumoral substances which produce their effects by interacting with presynaptic receptors located on postganglionic sympathetic nerves. Therefore, it is postulated that alterations in presynaptic regulation of norepinephrine release, resulting from changes in the functioning of one or more of these presynaptic receptors, may lead to a greater release of norepinephrine in the SHR. This review summarizes the results of studies evaluating presynaptic receptor mechanisms and norepinephrine release in the SHR. These studies suggest that norepinephrine release during sympathetic nerve stimulation is greater in the SHR and that alterations in some of the presynaptic receptor mechanisms may be responsible for this phenomenon.

Adenosine↗

PubMed1985

Enhancement of the pressor response to norepinephrine by angiotensin in the conscious rabbit.

The pressor interactions between angiotensin II and norepinephrine were investigated in conscious New Zealand white rabbits receiving a low sodium diet. Angiotensin II was administered continuously by intraperitoneal osmotic pumps in a subpressor dose so as to avoid the potentially confounding effects of experimentally-induced hypertension. Norepinephrine challenges were given as a series of graded intravenous boluses. During the 3 days of study the baseline blood pressure in the angiotensin-treated rabbits (n=10) did not differ from that in controls (n=10) whose intraperitoneal pumps contained only diluent. After 24 hours the systolic and diastolic blood pressure responses to norepinephrine in the angiotensin-treated group were, on average, 45% and 30% higher than in the controls; after 72 hours, they were 46% and 34% higher. Although the pressor amplitudes were increased by angiotensin II, they were not prolonged. Thus, facilitation by the subpressor angiotensin II of the blood pressure responses to norepinephrine did not seem dependent upon alterations in endogenous sympathetic mechanisms or the uptake of norepinephrine; nor could it be explained by sodium retention. It is possible that angiotensin II exhibits its effect by enhancing contractile responsiveness to norepinephrine at the postreceptor level.

Angiotensin II↗

PubMed1986

The facilitative actions of Bay K 8644 on norepinephrine and KCl-induced contractures of rabbit aortic rings.

The effect of the calcium channel agonist BAY K 8644 on the ability of KCl and norepinephrine to induce contractions of rabbit aortic rings has been examined in Krebs-Henseleit buffer containing either 4.0 or 6.8 mM potassium. BAY K 8644 (10(-8) to 10(-6) M) alone induced slowly developing aortic contractures which were 10 (at 4.0 mM potassium) or 20 (at 6.8 mM potassium) percent of the maximum obtainable with norepinephrine. These contractions were not observed in every experiment, but were more likely to occur at 6.8 mM (71% at 10(-6) M BAY K 8644) when compared to 4.0 mM (31% at 10(-6) M BAY K 8644) potassium buffer. BAY K 8644, in either potassium buffer, induced a statistically significant shift to the left in the norepinephrine dose-response curve. The norepinephrine dose-response curve was significantly curvilinear in the presence of 3 X 10(-8) M BAY K 8644 (6.8 mM potassium) and 10(-6) M BAY K 8644 (4.0 mM potassium). Similarly, BAY K 8644 induced sinistral shifts in the KCl dose-response curve with a curvilinear function observed at 3 X 10(-7) M BAY K 8644. These data show that BAY K 8644 is capable of inducing aortic contractures at potassium concentrations significantly lower than previously reported. Furthermore, BAY K 8644 facilitates opening of calcium channels by either potassium or norepinephrine. In contrast to others, our data indicates that BAY K 8644 can affect calcium channels activated by norepinephrine. Finally, our data suggest that the alpha and dihydropyridine receptors are capable of interacting and that occupation of one receptor can affect the action of a compound binding to the other receptor.

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

PubMed1990

Depletion of cardiac norepinephrine but not brain catecholamines by MPTP-N-oxide in mice.

After a single dose in mice, MPTP-N-oxide caused a dose-dependent depletion of cardiac norepinephrine which was similar although less pronounced than that caused by MPTP itself. After repeated daily doses, MPTP-N-oxide depleted cardiac norepinephrine, but did not deplete norepinephrine in the frontal cortex or dopamine in the striatum of mice. MPTP-N-oxide differed from MPTP, which depleted cardiac norepinephrine, cortical norepinephrine and striatal dopamine after repeated daily doses, but was similar to MPP+, another metabolite of MPTP, which depleted only cardiac norepinephrine. These data suggest that MPTP-N-oxide may contribute to the peripheral catecholamine-depleting effects after MPTP injection.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1988

Adipocyte responsiveness to norepinephrine in spontaneously hypertensive rats.

The present study describes the effect of norepinephrine on lipolysis and adenylate cyclase activity in adipocytes from Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The adipocytes were incubated in the presence of norepinephrine (10(-7) to 10(-4) mol/L) and the lipolytic activity was measured according to the accumulation of glycerol after one hour incubation. The results showed that norepinephrine induced a lower lipolytic activity in adipocytes from SH rats. cAMP-phosphodiesterase activities in adipocyte homogenates from WKY and SH rats were the same for both preparations. The effect of norepinephrine (10(-7) to 10(-4) mol/L) on adenylate cyclase activity in fat cell membranes from SH rats was decreased compared with WKY fat cell membranes. Adenylate cyclase activities in the presence of 10 mmol/L NaF were the same in both preparations. beta-receptor characteristics were examined, and the data demonstrate a statistically significant decrease in beta-receptor density in fat cell membranes from SH rats. The dissociation constants (Kd) were the same for WKY and SH preparations. This article suggests that adipocyte responsiveness to norepinephrine is decreased in SH rats. The decreased response to norepinephrine may be explained by a lower beta-receptor density in fat cell membranes from SH rats.

Adenylyl Cyclases↗

PubMed1993

Norepinephrine turnover and energy expenditure in Pima Indian and white men.

There is growing evidence of the involvement of sympathetic nervous system (SNS) activity in determining metabolic rate. Whole-body plasma norepinephrine turnover and its relationship to resting metabolic rate (RMR) and 24-hour energy expenditure (24EE) were compared in 14 Pima Indian men (25 +/- 4 years, 96 +/- 33 kg, 25% +/- 9% fat) and nine white men (25 +/- 3 years, 88 +/- 43 kg, 17% +/- 13% fat). Plasma norepinephrine turnover rate correlated strongly with body surface area (r = .76 and .54 for clearance and appearance, respectively) and fat-free mass (r = .74 and .52, respectively). However, independent of body size, there was no difference in either norepinephrine clearance or appearance rates between Pima Indian and white men. Norepinephrine appearance rate correlated positively with absolute values of 24EE and RMR, but not when adjusted for differences in body surface area or fat-free mass. However, norepinephrine appearance rate adjusted for differences in body size correlated with spontaneous physical activity. The results indicate that Pima Indian and white men have similar plasma norepinephrine appearance rates, but Pima Indians tend to be more resistant to beta-adrenergic stimulation. Although energy expenditure and SNS activity were not directly related, a higher SNS tone may either promote or reflect elevated levels of spontaneous physical activity and therefore influence both energy balance and body composition.

Adult↗

PubMed1982

Effect of PGI2 on the response of the ovine placenta to norepinephrine.

We have examined the effects of PGI2, 50 microgram/kg, on norepinephrine induced placental vasoconstriction in 6 chronically catheterized near-term sheep. Regional blood flows were measured with radioactive microspheres. Control flows were measured. Norepinephrine was than infused at 50 microgram/min throughout the experiment. After 15 min the blood flows were again measured and PGI2 was then added to the infusate at 50 microgram/min. In 15 min regional blood flows were again measured and the PGI2 infusion was stopped. Regional blood flows were measured for the last time 15 min later. The renal and nonplacental uterine vasculatures behaved in a predictable manner. There was constriction with norepinephrine but PGI2 opposed the effects of norepinephrine and decreased the resistance towards the normal levels. The placenta did not behave as did the other organs. Norepinephrine increased placental resistance but PGI2 did not decrease the resistance and severely depress the placental blood flows. PGI2 does not appear to oppose norepinephrine induced placental vasoconstriction.

Animals↗

PubMed1987

Evidence that dopamine regulates norepinephrine synthesis in the rat superior cervical ganglion during hypoxic stress.

Electrical stimulation of preganglionic nerves is known to increase norepinephrine synthesis in the rat superior cervical ganglion in vitro, an effect which appears to be partially regulated by a non-cholinergic transmitter. In the present study, we sought to determine whether sympathetic stimulation also increases norepinephrine synthesis in the rat ganglion in vivo, and whether dopamine released from ganglionic interneurons might regulate this response. To tackle these questions, rats were pretreated with spiroperidol, a selective dopamine-receptor blocker, and then were sympathetically stimulated by exposure to severe hypoxic stress. Other rats were pretreated with vehicle alone before the hypoxic exposure. Norepinephrine synthesis in ganglia was assessed by measuring endogenous tyrosine hydroxylase activity and norepinephrine turnover. We found that hypoxic stress increased both of these indices of norepinephrine synthesis, but only in rats pretreated with spiroperidol. No such response was detected in rats pretreated with vehicle. These results indicate that sympathetic stimulation increases norepinephrine synthesis in the rat superior cervical ganglion in vivo, and that dopamine released from interneurons might regulate this response.

Animals↗

PubMed1986

Requirement of gene transcription and protein synthesis for cold- and norepinephrine-induced stimulation of thyroxine deiodinase in rat brown adipose tissue.

The increase in propylthiouracil-insensitive 'type II' thyroxine 5'-deiodinase activity of brown adipose tissue was investigated in rats exposed to acute cold stress or single-dose norepinephrine injection. The 20-fold cold-induced increase in enzyme activity showed a 2-h lag phase and reached a maximum after only 8 h; reacclimation occurred with a 2-h time lag and a half-life of 2.2 h. 4 h after a single norepinephrine injection, the deiodinase activity was almost identical to that after a 4-h cold stress; norepinephrine could not potentiate the effect of the cold stress. Treatment with the protein synthesis inhibitor cycloheximide before exposure to cold or before norepinephrine injection totally blocked the increase in deiodinase activity, suggesting that the increase is due to de novo protein synthesis. The half-life of the enzyme in vivo was estimated to be 0.7 h. Treatment with the RNA synthesis inhibitor actinomycin D totally abolished the cold- and norepinephrine-induced increases, indicating that the increase requires mRNA synthesis. It was concluded that the dramatic cold-induced increase in thyroxine deiodinase activity in brown adipose tissue was not due to activation of preexisting enzyme but was fully due to a norepinephrine-induced increase in expression of the gene and subsequent synthesis of the protein.

Adipose Tissue, Brown↗