Biomedical subjects

O A Nedergaard

Publications and source records attributed to O A Nedergaard.

At least 19 recordsLinked to original sources

PubMed2000

Prejunctional muscarinic receptor modulation of noradrenaline release from sympathetic neurones in rabbit aorta.

The prejunctional muscarinic modulation of stimulation-evoked release of 3H-noradrenaline from sympathetic neurones in rabbit aorta was examined. The role of transmitter uptake, alpha-adrenoceptor blockade, stimulation frequency and endothelium on the modulation was investigated. Rings of aorta were incubated with (-)-3H-noradrenaline and subsequently subjected to electrical-field stimulation. Fractional 3H-overflow was determined by liquid scintillation counting. Acetylcholine (10(-8)-3 x 10(-6) M) added cumulatively, reduced the stimulation-evoked 3H-overflow up to 80%. The effect of acetylcholine was the same in intact and endothelium-free aorta. The inhibitory effect of acetylcholine was inversely related to the frequency of stimulation (1-10 Hz). The maximal inhibition (%) was 80 (1 Hz), 53 (3 Hz) and 14 (10 Hz). The inhibitory effect of acetylcholine (10(-6) M) and carbachol (10(-5) M) reached a maximum 15 min. after addition and then remained almost constant. Cocaine (3 x 10(-5) M) did not alter the effect of acetylcholine. Desipramine (10(-6) M) and corticosterone (4 x 10(-5) M) attenuated the inhibition seen with low concentrations (10(-8)-10(-7) M) of acetylcholine. The acetylcholine-induced inhibition was antagonized by desipramine. Cocaine plus corticosterone attenuated the inhibition seen with high concentrations (10(-6)-3 x 10(-6) M) of acetylcholine. Rauwolscine (10(-6) M) enhanced the maximal inhibitory effect of acetylcholine. We conclude that the inhibitory effect of acetylcholine on 3H-overflow from rabbit aorta preloaded with 3H-noradrenaline is (1) inversely related to stimulation frequency; (2) independent of endothelium; (3) unaffected by neuronal and extraneuronal transmitter uptake; (4) that cocaine is not a prejunctional muscarinic antagonist; (5) that cocaine, but not desipramine, is suited as a neuronal uptake inhibitor in studies of prejunctional muscarinic receptor subtypes; and (6) and that there is an inverse interaction between prejunctional alpha2-adrenoceptors and muscarinic receptors.

Acetylcholine↗

PubMed2000

Effect of omega-conotoxin GVIA on noradrenaline release from postganglionic sympathetic neurones in rabbit aorta.

The aim of the present work was to examine the effect of the selective N-type calcium blocking agent omega-conotoxin GVIA on stimulation-evoked release of noradrenaline from sympathetic nerves in rabbit isolated aorta with regard to stimulation frequency, extracellular Ca2+ concentration, and transmitter uptake. Rings of rabbit isolated aorta were preloaded with (-)-3H-noradrenaline and the fractional 3H-overflow evoked by electrical-field stimulation was determined by liquid scintillation spectrometry. Omega-conotoxin GVIA (3 x 10(-10)-3 x 10(-8) M) did not alter the spontaneous 3H-outflow. Omega-conotoxin GVIA (3 x 10(-10)-3 x 10(-8) M) caused a slowly developing reduction of stimulation-evoked 3H-overflow at 1 and 30 Hz. The Emax for the omega-conotoxin-induced inhibition was less (70%) at 30 Hz than that (96%) seen at 1 Hz. Short-term incubation with omega-conotoxin GVIA caused a subsequent steady-state inhibition. The inhibitory action of omega-conotoxin GVIA (3 x 10(-10)-3 x 10(-9) M) was inversely related to the extracellular Ca2+ concentration (6.5 x 10(-4)-2.7 x 10(-3) M). Cocaine (3 x 10(-5) M) plus corticosterone (4 x 10(-5) M), neuronal and extraneuronal uptake inhibitors, respectively, did not alter the inhibitory effect of omega-conotoxin GVIA (3 x 10(-9) M) on 3H-overflow evoked by stimulation at a frequency of either 1 or 30 Hz. It is concluded that omega-conotoxin GVIA acts on prejunctional N-type calcium channels to inhibit stimulation-evoked noradrenaline release from sympathetic neurone terminals in rabbit aorta. At a high frequency, another subtype calcium channel may possibly be involved. The action of omega-conotoxin GVIA is independent of neuronal and extraneuronal uptake mechanisms for noradrenaline, but dependent on the amount of Ca2+ to be transported across the neurilemma from the extracellular space into the neurone.

Animals↗

PubMed1999

Methodologic aspects of acetylcholine-evoked relaxation of rabbit aorta.

The acetylcholine-evoked relaxation of rabbit isolated thoracic aorta precontracted by phenylephrine was studied. Phenylephrine caused a steady contraction that was maintained for 6 h. In the presence of calcium disodium ethylenediaminetetraacetate (EDTA) and ascorbic acid the contraction decreased with time. N(G)-Nitro-L-arginine abolished the inhibitory effect of EDTA and ascorbic acid. Acetylcholine evoked a rapid concentration-dependent relaxation that recovered spontaneously and slowly, but fully, with time. Relaxation evoked by equieffective concentrations of carbachol and acetylcholine had the same time course. Cumulative addition of acetylcholine (10(-7)-3 x 10(-5) M) caused a marked relaxation that was reverted slightly at high concentrations. The relaxation was the same with rings derived from the upper, middle, and lower part of the thoracic aorta. Two consecutive concentration-response curves for acetylcholine obtained at a 2-h interval demonstrated a slight development of tachyphylaxis. The relaxation was inversely related to precontractile tension evoked by phenylephrine when expressed as a percentage, but independent when expressed as g tension. Storage of aorta in cold salt solution for 24 h did not alter the relaxation. EDTA and ascorbic acid did not alter the relaxation. It is concluded that (1) EDTA and ascorbic acid can not be used with impunity to stabilize catecholamines used as preconstriction agents; (2) the reversal of the acetylcholine-evoked relaxation is not due to hydrolysis of acetylcholine; (3) the relaxation is uniform in all segments of thoracic aorta; (4) cold storage of aorta does not alter the relaxation; and (5) acetylcholine releases the same amount of relaxing factor, irrespective of the precontractile tension.

Acetylcholine↗

PubMed1999

Modulation of norepinephrine release from sympathetic neurons of the rabbit aorta by prejunctional prostanoid receptors.

The pharmacological properties and subtypes of prostanoid receptors involved in the prejunctional modulation of [(3)H]norepinephrine release from sympathetic neurons were studied using isolated rabbit aorta. Rings preincubated with [(3)H]norepinephrine were washed with physiological salt solution that contained cocaine plus corticosterone, uptake(1) and uptake(2) inhibitors, respectively, and rauwolscine to block prejunctional alpha(2)-adrenoceptors. Electrical field stimulation was used to evoke (3)H overflow. Prostaglandin (PG)E(2) (10(-9) to 3 x 10(-7) M) reduced the stimulation-evoked (3)H overflow; the pEC(50) value was 8.3, and E(max) value was 98%. This effect was also seen with PGE(1), PGD(2), PGF(2alpha), the EP(1)/EP(3) receptor agonist sulprostone, the EP(2)/EP(3) receptor agonist misoprostol, and the EP(1)/IP receptor agonist iloprost; the rank order (pEC(50)) was sulprostone (8.4) > PGE(2) (8.3) > misoprostol (8.1) > PGE(1) (7.9) > PGF(2alpha) (6.0) > PGD(2) (<5.0). This rank order suggests that these agents act on prejunctional prostaglandin receptors of the EP(3) subtype. The stable thromboxane A(2) analog U46619 (9,11-dideoxy-11alpha, 9alpha-epoxymethano-PGF(2alpha)) slightly reduced the stimulation-evoked (3)H overflow. The FP receptor agonist fluprostenol and the EP(2) receptor agonist butaprost had no effect. The EP receptor antagonist AH6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) did not alter the inhibitory effect of PGE(2) and sulprostone. AH6809 did not modulate the stimulation-evoked (3)H overflow. This suggests that prejunctional EP(1) receptors are not involved. The IP receptor agonist cicaprost reduced the (3)H overflow only at concentrations higher than 3 x 10(-5) M. We conclude that the postganglionic sympathetic neurons in rabbit aorta are endowed with prejunctional inhibitory EP(3) receptors. FP and IP receptors are not present, and the possible presence of inhibitory DP receptors requires further study.

Animals↗

PubMed1997

Prejunctional modulation by angiotensins of noradrenaline release from sympathetic neurons in isolated rabbit aorta.

The aims of the present work were to compare the modulating effect of angiotensins I, II, III, IV and (1-7) [AI, AII, AIII, AIV and A(1-7) respectively] on stimulation-evoked noradrenaline release from postganglionic sympathetic nerves in rabbit isolated aorta; to examine the influence of inhibiting the neuronal and extraneuronal uptake of noradrenaline on the modulating effect of AII and thirdly, to determine the role of angiotensin converting enzyme (ACE) in the modulating effects of AI and AII and the role of aminopeptidases A and M in the effects of AII and AIII. Rings of aorta were preloaded with (-)-3H-noradrenaline and then subjected to electrical field stimulation. Cumulative addition of AI (10(-8)-10(-6) M), AII (3 x 10(-11)-10(-8) M) and AIII (3 x 10(-10)-10(-6) M) enhanced the stimulation-evoked 3H-overflow up to 142, 165 and 188% respectively. The order of potency was AII > AIII > AI. AIV (10(-10)-10(-7) M) and A(1-7) (10(-10)-10(-7) M) caused no change. Single concentrations (10(-9)-10(-7) M) of AI, AII and AIII caused initial enhancement which subsequently decreased, i.e. development of tachyphylaxis. The effect of AII was independent of stimulation frequency at 1-10 Hz, but absent at 30 Hz. Cocaine (3 x 10(-5) M) plus corticosterone (4 x 10(-5) M) did not alter the enhancing effect of AII. CaNa2EDTA (3 x 10(-5) M) did not alter the enhancing effect of AI. Captopril (10(-6) and 10(-5) M) and lisinopril (10(-6) M) attenuated the enhancing effect of AI. Captopril and lisinopril (both 10(-6) and 10(-5) M) did not alter the enhancing effect of AII. Captopril (10(-7)-10(-4) M) and lisinopril (10(-7)-10(-4) M) themselves did not alter the stimulation-evoked 3H-overflow. Amastatin (10(-5) M) increased the enhancement seen with AIII (3 x 10(-11)-10(-9) M) but did not alter the enhancing effect of AII (10(-9)-10(-8) M). Amastatin (10(-9)-10(-5) M) had no effect on the stimulation-evoked 3H-overflow. It is concluded that AI, AII and AIII facilitate the stimulation-evoked 3H-noradrenaline release to various degrees (relative order of potency: AII > AIII > AI and of efficacy: AIII > AII > AI). The estimates may be compromised by the development of tachyphylaxis. The facilitation by AII was independent of the neuronal and extraneuronal uptake mechanisms. The action of AI is in part due to its conversion to AII. The effect of AIII was probably underestimated due to its degradation to AIV. AII is apparently not a substrate for aminopeptidase M.

Aminopeptidases↗

PubMed1997

Prejunctional modulation by prostaglandin E2 of noradrenaline release from sympathetic neurones in rabbit aorta.

The modulating effect of prostaglandin E2 (PGE2) on the electrically-evoked 3H-overflow from rabbit isolated aorta preloaded with 3H-noradrenaline was examined. PGE2 (3 x 10(-9)-3 x 10(-7) M) inhibited the stimulation-evoked 3H-overflow (maximum inhibition: 81%; pIC50: 8.1). The inhibition was reversible and inversely related to stimulation frequency (1-30 Hz). Cocaine (3 x 10(-5) M) and corticosterone (4 x 10(-5) M) did not alter the inhibitory effect of PGE2 (3 x 10(-9)-10(-7) M). Rauwolscine (10(-6) M) enhanced the reduction caused by PGE2 (3 x 10(-9)-10(-7) M). Rauwolscine (10(-6) M) alone enhanced the 3H-overflow by 360%. Indomethacin (3 x 10(-6) M) and suprofen (4 x 10(-5) M) did not alter the PGE2 (3 x 10(-9)-10(-7) M)-induced reduction of the 3-H-overflow. Indomethacin (3 x 10(-6) M) and suprofen (4 x 10(-5) M) alone had no effect. We conclude that in the rabbit aorta (1) PGE2 modulates noradrenaline release from sympathetic neurones through a prejunctional inhibitory receptor mechanism; (2) that there is an interaction between alpha 2-adrenoceptors and EP-receptors; (3) that uptake inhibition does not affect the effect of PGE2; and (4) that the influence of endogenous prostaglandins on the noradrenaline release can be excluded.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed1996

Effect of dopexamine hydrochloride on sympathetic neuroeffector transmission in rabbit isolated pulmonary artery.

The effects of dopexamine hydrochloride on sympathetic neuroeffector transmission were studied in rabbit isolated pulmonary artery. Short-term exposure of dopexamine (10(-8) x 10(-7) M) and cocaine (10(-6)-3 x 10(-5) M), but not desipramine (3 x 10(-9)-3 x 10(-7) M), to the artery enhanced the contractions evoked by electrical-field stimulation. Corticosterone (4 x 10(-5) M), corticosterone (4 x 10(-5) M) plus cocaine (3 x 10(-8) M), but not cocaine (3 x 10(-5) M), attenuated the enhancement seen with dopexamine. High concentrations of dopexamine (10(-5)-3 x 10(-5) M), cocaine (10(-4) M), and desipramine (10(-6)-10(-5) M) decreased the stimulation-evoked contractions. Dopexamine (10(-7)-3 x 10(-5) M), but neither cocaine nor desipramine, caused an increase in resting tension that waned with time. Corticosterone (4 x 10(-5) M), but not cocaine (3 x 10(-5) M), attenuated the increase in resting tension. Propranolol (10(-6) M) did not alter the enhancing and inhibitory effects of dopexamine. A single concentration (10(-7) and 10(-6) M) of either dopexamine or desipramine caused a time-dependent biphasic response as regards the repetitive stimulation-evoked contractions of pulmonary artery: initial enhancement followed by inhibition. The inhibitory effect of dopexamine (10(-6) M) and desipramine (3 x 10(-6) M) seen after prolonged exposure was almost irreversible and partially reversible, respectively, by washing the preparations with drug-free salt solution. Cocaine caused a monophasic steady-state response: either enhancement (10(-5) M) or inhibition (2 x 10(-4) M). In both cases, the onset was rapid. The reduction caused by cocaine (2 x 10(-4) M) and by prazosin (10(-9) M) was fully reversed. Dopexamine (10(-5) M) antagonized competitively the contractions evoked by noradrenaline (3 x 10(-9)-10(-4) M). It is concluded that (1) the dopexamine-induced enhancement of neurogenic contractions is not due to either inhibition of neuronal and extraneuronal uptake of noradrenaline or an agonist action on prejunctional beta 2-adrenoceptors; (2) that the dopexamine-induced inhibition of stimulation-evoked contraction is due to an inhibition of postjunctional alpha 1-adrenoceptors; and (3) that the dopexamine-induced increase in resting tension is due to its metabolite methyldopexamine.

Animals↗

PubMed1995

Role of cyclic AMP in stimulation-evoked release of 3H-noradrenaline from rabbit isolated ear artery.

The possible involvement of cyclic AMP in the stimulation-evoked 3H-overflow from rabbit isolated ear artery preloaded with 3H-noradrenaline was studied. Cyclic AMP (10(-5)-3 x 10(-4)M), 8-bromo-cyclic AMP (3 x 10(-4)M) and adenosine (10(-5)-3 x 10(-4)M) enhanced stimulation-evoked 3H-overflow. Dibutyryl-cyclic AMP (10(-5)-3 x 10(-4)M) had no effect. Theophylline (3 x 10(-5)M) and the phosphodiesterase inhibitor AH 21-132 (3 x 10(-5)M) did not alter the enhancement of 3H-overflow caused by either cyclic AMP or adenosine. Forskolin (3 x 10(-6)M) and the phosphodiesterase inhibitors ICI 63 197 (10(-4)M) and AH 21-132 (3 x 10(-6)-3 x 10(-5)M) increased stimulation-evoked 3H-overflow. Forskolin (10(-6)M) enhanced the effect of ICI 63 197 (3 x 10(-5)M) but it did not alter the effect of AH 21-132. It is concluded that cyclic AMP is involved in the stimulation-evoked release of noradrenaline from postganglionic sympathetic nerves in the rabbit ear artery.

Adenosine↗

PubMed1995

Release of 3H-5-hydroxytryptamine from isolated rabbit aorta.

The main aim of the present investigation was to study systematically the passive and stimulation-evoked release of 3H-5-hydroxytryptamine (3H-5-HT) from rabbit isolated aorta. This was accomplished by preloading rings of aorta with 3H-5-HT (10(-6)M) and then monitoring by fractional collection the basal 3H-outflow and stimulation-evoked 3H-overflow. The basal 3H-outflow from aorta preloaded with 10(-6)M of either 3H-5-HT or (-)-3H-noradrenaline (3H-NA) leveled off about 100 min. after the onset of wash-out and remained almost constant thereafter (100-240 min.). The basal 3H-outflow from tissue preloaded with 3H-5-HT was almost 3-fold higher (70-240 min.) than that seen after preloading with 3H-NA. Cocaine (3 x 10(-5)M) did not alter the basal 3H-outflow (15-240 min.) from tissue preloaded with 3H-5-HT, while pargyline (5 x 10(-4)M) decreased it by about 66% (100-240 min.). Electrical-field stimulation (S1-S7, 200 mA, 600 pulses, 0.5 msec., 3 Hz) were applied to the tissue. The initial stimulation-evoked 3H-overflow from aorta preloaded with 3H-5-HT was higher than the subsequent ones (S1-S7; 100, 35, 35, 35, 35, 37, and 40%). Similar results to these were obtained with tissues preloaded with 3H-NA. The stimulation (S1-S7; 200 mA). 600 pulses, 0.5 msec, 3 Hz)-evoked 3H-overflow increased in an apparent linear manner with the amount of current used (50-200 mA).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Inhibition by (-)-deprenyl of agonist-evoked contractions in rabbit aorta.

The effect of (-)-deprenyl, a relatively selective MAO-B inhibitor, was examined for its ability to inhibit the contractions of rabbit isolated aorta evoked by various agonists and potassium. (-)-Deprenyl (10(-5)-3 x 10(-4) M) antagonized the contractions evoked by noradrenaline (10(-8)-3 x 10(-4) M); pA2: 5.10. The antagonism was reversible. It was attenuated by cocaine (3 x 10(-5) M); pA2: 4.38, unchanged by corticosterone (4 x 10(-5) M); pA2 4.79 and enhanced by cocaine (3 x 10(-5) M) plus corticosterone (4 x 10(-5) M); pA2: 5.48. (+)-Deprenyl (10(-6)-10(-4) M) did not alter the contractions evoked by noradrenaline (3 x 10(-9)-10(-4) M). Clorgyline (10(-5) and 10(-4) M) antagonized the noradrenaline-evoked contractions. Pargyline (10(-4) and 3 x 10(-4) M) had no effect. (-)-Deprenyl (10(-5)-3 x 10(-4) M) antagonized the contractions evoked by phenylephrine (10(-8)-10(-4) M); pA2: 5.10. Removal of the endothelium did not alter the antagonism; pA2: 5.35. (-)-Deprenyl (10(-5)-3 x 10(-4) M) antagonized the contractions evoked by either 5-hydroxytryptamine (3 x 10(-8)-3 x 10(-4) M); pA2: 4.61 or by histamine (10(-6)-3 x 10(-2) M); pA2: 4.84. (-)-Deprenyl (3 x 10(-4) M) caused a noncompetitive antagonism of the contractions evoked by potassium (1.5-5.5 x 10(-2) M). It is concluded that (-)-deprenyl is a weak inhibitor of postjunctional alpha 1-adrenoceptors, 5-hydroxytryptamine (5-HT2) receptors, and histamine (H1) receptors.

Adrenergic alpha-Antagonists↗

PubMed1994

Effect of dopexamine hydrochloride on contractions of rabbit isolated aorta evoked by various agonists.

The inhibitory affinity of dopexamine hydrochloride to postsynaptic adrenoceptors, cholinoceptors, 5-hydroxytryptamine and histamine receptors was studied in rabbit isolated aorta. Dopexamine (10(-7)-10(-5) M) antagonized competitively the contractions of rabbit aorta evoked by noradrenaline (pA2: 6.60). Neither cocaine plus corticosterone nor cocaine, corticosterone plus propranolol altered the inhibition (pA2: 6.77 and 6.63, respectively). The antagonism of dopexamine against noradrenaline-evoked contractions was the same after 1 and 4 hr of pretreatment with dopexamine. In the presence of cocaine plus corticosterone, dopexamine antagonized the contractions evoked by phenylephrine (pA2: 6.94). Removal of endothelium did not influence this antagonism (pA2: 7.06). Dopexamine (10(-7)-10(-5) M) did not antagonize the contractions of aorta evoked by histamine (3 x 10(-7)-6 x 10(-5) M) and by 5-hydroxytryptamine (3 x 10(-7)-3 x 10(-4) M). Dopexamine (10(-8 and 10(-7) M) did not alter the contractions of endothelium-free aorta evoked by carbachol. Dopexamine (10(-7)-10(-5) M) slightly enhanced the contractions of aorta evoked by potassium (10(-2)-5.5 x 10(-2) M). These results suggest that dopexamine is an alpha 1-adrenoceptor antagonist. Furthermore, dopexamine has no affinity to cholinoceptors, histamine and 5-hydroxytryptamine (5-HT2) receptors and is apparently not a calcium antagonist.

Adrenergic Agonists↗

PubMed1992

Effects of xylamine on vascular neuroeffector transmission.

The effect of xylamine on sympathetic neuroeffector transmission in rabbit isolated blood vessels was examined. Xylamine (10(-8) to 10(-6) M) caused a slowly progressing inhibition of the contractions of pulmonary artery evoked by electrical field stimulation. The inhibition was irreversible. Cocaine (3 x 10(-5) M) prevented the inhibitory action of xylamine (10(-7) M), but it did not reverse the inhibition caused by xylamine (10(-6) M). Xylamine (10(-7) to 3 x 10(-5) M) reduced the accumulation of [3H]norepinephrine (NE) (10(-8) M). In the presence of desipramine (10(-6) M), xylamine (10(-7) to 3 x 10(-5) M) and corticosterone (10(-6) to 10(-4)) reduced the 3H-accumulation. Xylamine (10(-7) to 10(-5) M) reduced the tissue NE content by up to 50%. Xylamine (10(-7) to 10(-6) M) antagonized in a noncompetitive manner the contractions of aorta evoked by NE (10(-9) to 3 x 10(-5) M), histamine (10(-6) to 3 x 10(-4) M) and 5-hydroxytryptamine (10(-8) to 3 x 10(-4) M). In the case of NE, the antagonism was more marked in the presence of either cocaine (3 x 10(-5) M) plus corticosterone (4 x 10(-5) M) or corticosterone (4 x 10(-5) M). In the presence of xylamine (10(-7) to 10(-6) M), cumulative addition of near maximally effective concentrations of NE, 5-hydroxytryptamine and histamine caused a progressive and complete relaxation of aorta. Xylamine (10(-7) to 10(-5) M) did not alter the contractions of aorta evoked by potassium (17-55 mM). The results support the contention that xylamine is an inhibitor of neuronal and extraneuronal uptake, an adrenergic neurone blocking agent and a noncompetitive antagonist of alpha-1 adrenoceptors, histamine and 5-hydroxytryptamine2 receptors. Xylamine is not a direct acting vasodilator on smooth muscle.

Animals↗

PubMed1991

Lack of presynaptic modulation by isoprenaline of 3H-noradrenaline release from rabbit isolated ear artery.

The aim of the present investigation was to examine whether or not presynaptic facilitatory beta-adrenoceptors are detectable on the postganglionic nerves in the rabbit isolated ear artery. Strips of rabbit central ear artery were incubated with 3H-noradrenaline (10(-7) mol/l; 30 min or 10(-6) mol/l; 60 min). Subsequently, they were washed repeatedly with physiological salt solution. The strips were subjected to electrical-field stimulation (S1-S8) and the resultant 3H-overflow was determined. When the ear artery was stimulated with 150 pulses (0.5 ms; 3 Hz; 225 mA), isoprenaline (10(-9)-10(-6) mol/l) either alone or in the presence of either rauwolscine (10(-6) mol/l) or phentolamine (10(-6) mol/l) did not alter the stimulation-evoked 3H-overflow. This was also the case in the presence of rauwolscine (10(-6) mol/l) plus either the selective phosphodiesterase inhibitor ICI 63 197 (3 x 10(-5) mol/l) or forskolin (10(-6) mol/l). When the ear artery was stimulated with 300 pulses (1 ms; 5 Hz; 225 mA), isoprenaline had no effect on the stimulation-evoked 3H-overflow. This was also the case when phentolamine (10(-6) mol/l) was present. Propranolol (10(-7)-10(-5) mol/l) did not alter the stimulation-evoked 3H-overflow. In some experiments, the stimulation current was reduced to 175 mA in order to obtain similar reference release (S3) values despite the presence of rauwolscine (150 pulses; 0.5 ms; 3 Hz). Even then, isoprenaline (10(-9)-10(-6) mol/l) did not change stimulation-evoked 3H-overflow. The results suggest that postganglionic sympathetic nerves in rabbit central ear artery do not possess presynaptic facilitatory beta-adrenoceptors.

Animals↗

PubMed1991

Presynaptic modulation by adrenaline of 3H-noradrenaline release in rabbit ear artery.

The aim of the present investigation was to examine the ability of adrenaline to modulate presynaptically the stimulation-evoked release of noradrenaline from postganglionic sympathetic nerves in the rabbit ear artery. Strips of rabbit central ear artery were incubated with 3H-noradrenaline. Subsequently, they were washed repeatedly with physiological salt solution containing cocaine and corticosterone. The strips were subjected to repeated electrical-field stimulation (S1-S8, 150 pulses, 0.5 ms, 225 mA, 3 Hz) and the resultant 3H overflow was determined. Adrenaline (10(-8) to 10(-6) mol/l) and clonidine (10(-9) to 10(-6) mol/l) reduced the stimulation-evoked 3H overflow. Rauwolscine (10(-7) to 10(-5) mol/l) and phentolamine (3 x 10(-7) to 3 x 10(-5) mol/l) enhanced markedly the stimulation-evoked 3H overflow. Rauwolscine (10(-6) mol/l) abolished the inhibitory effect of low concentrations of adrenaline (10(-8) to 10(-7) mol/l) and clonidine (10(-9) to 10(-7) mol/l) and attenuated the inhibitory effect of the highest concentration (10(-6) mol/l) of clonidine, but not that of adrenaline. In some experiments, the stimulation current was reduced to 175 mA in order to obtain similar reference release (S3) values despite the presence of rauwolscine. Even then, only the highest concentration (10(-6) mol/l) of adrenaline decreased the stimulation-evoked 3H overflow. Facilitation was not seen. It is concluded that adrenaline activates inhibitory presynaptic alpha 2-adrenoceptors. Furthermore, adrenaline does not reveal the presence of presynaptic facilitatory beta-adrenoceptors in the rabbit ear artery.

Animals↗

PubMed1990

pH in physiological salt solutions: direct measurements.

Calculations of pH in modified Krebs solutions by inserting PCO2 and total-CO2 in the Henderson-Hasselbalch (H.-H.) equation are obvious as the equation originally served for this purpose. An exact calculation of the relation between pH and PCO2 is complicated as the concentration of bicarbonate, the dissociation constant and the solubility of CO2 change. Furthermore, the dissociation constant in the H.-H. equation is constant only if activities are used in the equation instead of stoichiometric concentrations. We therefore investigated the influence of different carbon dioxide tensions and bicarbonate concentrations on directly measured pH of organ baths aerated with mass-spectrometric analyzed O2-CO2 gases. For reference precision buffers were used. The measured pH values differed distinctly from calculated pH values in the acidic and alkaline parts of the pH interval investigated (6.57-8.15). Measurements of actual pH with proper calibration standards therefore seem mandatory.

Bicarbonates↗

PubMed1990

Release of 3H-noradrenaline from rabbit isolated ear artery.

The stimulation-evoked 3H-overflow from rabbit isolated ear arteries preincubated with 3H-noradrenaline was studied. Three strips were derived from each central artery. The strips were incubated (30 min.) with 3H-noradrenaline (10(-7) M) and the spontaneous 3H-outflow and stimulation-evoked 3H-overflow were followed by fractional collection. After a wash-out period (75 min.), the strips were stimulated (225 mA; 150 monophasic pulses; 3 Hz; 0.5 msec.) several times. The initial stimulation-evoked 3H-overflow (S1) was about 5-fold higher than the subsequent five 3H-overflows (S2-S6) which remained almost constant. Bretylium (10(-5) M), tetrodotoxin (10(-6) M), and omission of Ca2+ from the physiological salt solution reduced the stimulation-evoked 3H-overflow by maximally 52%, 77% and 62%, respectively. An increase in stimulation current from 50 to 225 mA caused a continuous rise in stimulation-evoked 3H-overflow, which tended to be Ca2(+)-sensitive. The stimulation-evoked 3H-overflow was frequency-dependent: at 1-4 Hz, the 3H-overflows were the same; at 8 and 16 Hz, they increased. Cocaine (3 x 10(-5) M) plus corticosterone (4 x 10(-5) M) enhanced the stimulation-evoked 3H-overflow at 1-8 Hz, while it had no effect at 16 Hz. Propranolol (3 x 10(-7) M) did not antagonize this enhancement. An increase in number of pulses from 10 to 1000 in the stimulus caused a corresponding rise in the evoked 3H-overflow. This was also the case when cocaine plus corticosterone were present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Modulation of noradrenaline release by activation of presynaptic beta-adrenoceptors in the cardiovascular system.

Peripheral sympathetic nerve terminals in many tissues, but not all, are endowed with beta-adrenoceptors. Activation of these result in an enhancement of noradrenaline release evoked by electrical nerve stimulation. These so-called presynaptic beta-adrenoceptors are possibly located on the outer surface of the varicosity of the noradrenergic nerves. A postsynaptic location, however, is also a possibility. The presynaptic beta-adrenoceptors appear to be of the beta 2-adrenoceptor subtype. However, specific classification is lacking. The stereospecificity of the beta-adrenoceptors is controversial. These receptors are not activated by noradrenaline released from sympathetic nerves. Adrenaline derived from the adrenal medulla may be the physiological activator. Either circulating adrenaline or adrenaline taken up by sympathetic nerve terminals and then released as a cotransmitter with noradrenaline activates the presynaptic beta-adrenoceptors. In the latter case, a "positive" feedback" loop may be formed.

Adrenergic beta-Agonists↗

PubMed1989

Carbon dioxide tensions in physiological salt solutions: direct measurements.

Carbon dioxide tensions were measured directly in organ baths and a tonometer aerated in parallel with 6 different gas mixtures of O2 and CO2, 3 gas flows, 3 equilibration periods, and 3 bicarbonate concentrations. The measured partial pressure of carbon dioxide differed systematically from expected values, probably due to errors in the carbon dioxide measurement system. In conclusion, carbon dioxide equilibrates with the bubbling gas in the baths as well as in the tonometer to an almost perfect equilibration.

Bicarbonates↗