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D C Eikenburg

Publications and source records attributed to D C Eikenburg.

At least 19 recordsLinked to original sources
PubMed1999

Differential effects of epinephrine and norepinephrine on cAMP response and g(i3)alpha protein expression in cultured sympathetic neurons.

The effect of 24-h pretreatment with epinephrine (EPI) or norepinephrine (NE) on alpha(2)- and beta-adrenoceptor agonist-induced, cAMP responses and G(i3)alpha-protein expression was studied in primary cultures of rat superior cervical ganglionic (SCG) neurons. SCG neurons, 10 to 12 days in culture, accumulated cAMP when stimulated with the beta-adrenoceptor agonist isoproterenol and the preferential beta(2)-adrenoceptor antagonist ICI 118,551 blocked this response. Similarly, the preferential alpha(2)-adrenoceptor agonist UK14,304 inhibited forskolin-stimulated cAMP accumulation, implying that cultured SCG neurons possess functional alpha(2)- and beta(2)-adrenoceptors. A 24-h treatment of SCG neurons with EPI or NE induced desensitization of the cAMP response to the beta-adrenoceptor agonist isoproterenol. Simultaneously, EPI treatment increased the maximal inhibitory cAMP response to the alpha(2)-adrenoceptor agonist UK14,304 and NE was without effect. Immunoblotting analyses of G(i3)alpha subunits revealed that 24-h EPI but not NE treatment induces a 3- to 4-fold increase in the expression of G(i3)alpha subunits. Furthermore, EPI-induced up-regulation of alpha-subunit expression can be blocked by the preferential beta(2)-adrenoceptor antagonist ICI 118,551 but not by the preferential beta(1)-adrenoceptor antagonist CGP 20712A. Our results suggest that changes in alpha(2)-adrenoceptor responsiveness induced by EPI may involve activation of beta(2)-adrenoceptors that influence the expression of inhibitory G proteins. Thus, primary cultures of sympathetic neurons by possessing functional alpha(2)- and beta-adrenoceptors may be a suitable model system to study the signaling mechanisms of "cross talk" between these adrenoceptor subtypes, which are known to play a central role in cardiovascular function.

Adrenergic Agonists↗
PubMed1996

Prejunctional alpha adrenoceptor desensitization in rat heart after chronic epinephrine treatment.

This study examines the effects of acute incorporation of epinephrine (EPI) into cardiac catecholamine stores and chronic elevation of plasma EPI concentrations on sympathetic neurotransmission and adrenoceptor modulation in the rat heart. Chronic elevation of plasma EPI was accomplished by infusion of EPI (100 micrograms/kg/hr s.c.) for 6 days via osmotic minipumps. Vehicle-treated animals served as controls. The cardiac catecholamine stores of the vehicle-treated group consisted of norepinephrine only. Chronic EPI treatment resulted in incorporation of EPI (90% of total catecholamines) without a significant change in the total cardiac catecholamine content. At 0.1 to 1 Hz, stimulus-induced catecholamine overflows in the EPI-treated group consisted of both norepinephrine and EPI and were 66 to 70% higher than those of the vehicle-treated group. A preferential beta-2 adrenoceptor antagonist, ICI 118,551 (1 nM-1 microM) did not alter catecholamine overflows in either group. In contrast, a preferential alpha-2 adrenoceptor antagonist, idazoxan (1 microM), significantly increased catecholamine overflow in the vehicle-treated group but not in the EPI-treated group. After idazoxan treatment, the significant difference between overflows in the chronic vehicle- and EPI-treated groups was abolished. Acute EPI treatment in vitro (1 microM, 1 hr in the presence of phentolamine 10 microM; nadolol, 30 microM) resulted in incorporation of EPI (75% of total catecholamine) into cardiac catecholamine stores and increased the stimulus-induced catecholamine overflow at 0.1 Hz. Blockade of prejunctional beta-2 adrenoceptors abolished the difference between the acute EPI- and vehicle-treated groups. Moreover, the increase in catecholamine overflow resulting from alpha-2 adrenoceptor blockade with idazoxan (1 microM) was comparable between the acute EPI- and vehicle-treated groups. These results suggest that 1) both chronic elevation of plasma EPI and acute incorporation of EPI into cardiac neurotransmitter stores result in facilitation of neurotransmitter release and 2) prejunctional beta adrenoceptor activation appears to be the cause of the increase after acute EPI incorporation, whereas desensitization of prejunctional alpha-2 adrenoceptors, not beta-2 adrenoceptor-mediated facilitation, is the cause of the enhanced overflow after chronic EPI treatment.

Animals↗
PubMed1995

Role of prejunctional beta adrenoceptors in rat cardiac sympathetic neurotransmission.

This study examines the role of prejunctional beta adrenoceptors in the modulation of sympathetic neurotransmission in the rat heart. Under anesthesia, the heart with right cardiac sympathetic nerves attached was isolated and perfused with Krebs' bicarbonate buffer containing cocaine (10 microM), corticosterone (40 microM) and atropine (6 microM). Stimulation of sympathetic nerves at frequencies of 0.05 to 3 Hz (15 pulses, supramaximal voltage, 2-msec pulse duration) produced a pronounced frequency-dependent increase in heart rate. A maximal increase of 89 +/- 10 bpm was obtained at 3 Hz. Propranolol (0.1 microM) had no significant effect on the stimulus-induced NE overflow in the absence and presence of alpha adrenoceptor blockade alone or combined with adenosine receptor blockade. The beta-2 adrenoceptor agonist salbutamol increased stimulus-induced NE overflow (15 pulses) at 0.1 Hz but not at 0.5 Hz. Alpha adrenoceptor blockade did not alter the salbutamol-evoked facilitation at 0.1 Hz but revealed salbutamol-evoked facilitation at 0.5 Hz. Salbutamol did not alter NE overflow at 1 Hz even in the presence of alpha adrenoceptor blockade. In conclusion, prejunctional beta adrenoceptor facilitation of NE overflow is frequency and alpha adrenoceptor modulated. At low frequency (0.1 Hz), beta adrenoceptor-mediated facilitation is maximal and alpha adrenoceptor independent; at intermediate frequency (0.5 Hz) it is alpha adrenoceptor restrained and it is absent at 1 Hz. Finally, NE does not modulate its own release via the prejunctional beta adrenoceptors.

Albuterol↗
PubMed1994

Pharmacological characterization and anatomical localization of prejunctional beta-adrenoceptors in the rat kidney.

1. The subtype and anatomical localization of beta-adrenoceptors mediating facilitation of stimulus-induced overflow of noradrenaline ('prejunctional beta-adrenoceptors') are not conclusively known to date. The present study was undertaken to characterize these receptors by use of pharmacological methods as well as to define their localization (prejunctional or postjunctional) with radio-ligand binding and autoradiography techniques combined with surgical denervation of the sympathetic innervation to the rat kidney. 2. Exposure of the kidney to (-)-isoprenaline, the nonselective beta-adrenoceptor agonist, resulted in a dose-dependent facilitation of stimulus-induced neurotransmitter overflow. This response was inhibited by propranolol, the beta 1- and beta 2-adrenoceptor antagonist, with a pA2 of 9.20 suggesting that the prejunctional beta-adrenoceptors are not of the beta 3-subtype. 3. The rank order of potency and potency ratios of beta-adrenoceptor agonists at renal prejunctional beta-adrenoceptors (EC50 for agonist/EC50 for (-)-isoprenaline) were: (-)-isoprenaline (1) > procaterol (2) > salbutamol (3) > adrenaline (10) > (+)-isoprenaline (25). However, dobutamine, the beta 1-adrenoceptor agonist, failed to enhance stimulus-induced overflow of noradrenaline. These results are indicative of the presence of beta 2-adrenoceptors as prejunctional beta-adrenoceptors. 4. Facilitation elicited by (-)-isoprenaline and procaterol, the selective beta 2-adrenoceptor agonist, was inhibited by ICI 118,551, the selective beta 2-adrenoceptor antagonist, with pKb values of 9.20 and 9.35, respectively at renal prejunctional beta-adrenoceptors. Similarly, the pKb values of metoprolol, the selective beta 1-adrenoceptor antagonist, at renal prejunctional beta-adrenoceptors were determined to be 6.25 and 6.18 against (-)-isoprenaline and procaterol, respectively. These results suggest the presence of a homogeneous population of beta 2-adrenoceptors as prejunctional beta-adrenoceptors. 5. Radio-ligand binding analysis of renal beta-adrenoceptors revealed the prevalence of the beta 1-subtype as compared to the beta 2-subtype (63% vs 37%). However, surgical denervation of the rat kidney, resulting in more than 90% reduction in renal noradrenaline content, selectively reduced the beta 2-adrenoceptor population by 80%, implying the presence of beta 2-adrenoceptors on renal sympathetic nerve terminals. 6. Autoradiographic analysis demonstrated the presence of beta 1-adrenoceptors on cortical structures such as glomeruli and tubules. beta-Adrenoceptors were found to be present on tubules (minor population), collecting tubules in outer medulla and the adventitia and adventitial-medial border of intraparenchymal branches of the renal artery. Surgical denervation of the rat kidney resulted in the disappearance of Beta2-adrenoceptors associated with the intraparenchymal branches, without affecting the Beta-adrenoceptor populations at other sites. These results support the notion that the Beta2-subtype is present on renal sympathetic nerve terminals and demonstrate that these prejunctional Beta2-adrenoceptors are associated with the renal vasculature and not with renal tubules.7. The results of the present investigation demonstrate that renal prejunctional Beta-adrenoceptors are of the Beta2-subtype in nature. These receptors are present on sympathetic nerve terminals which are associated with the renal vasculature.

Animals↗
PubMed1993

Dependence of prejunctional beta-adrenoceptor facilitation of sympathetic neurotransmission on stimulus train length and agonist exposure time.

Prejunctional beta-adrenoceptors facilitate stimulus-induced neuronal norepinephrine release in the rat kidney. The mechanism(s) responsible for the bell-shaped concentration-facilitatory response curve to isoproterenol generated in the presence of alpha-adrenoceptor blockade and uptake blockade was explored. The concentration-response curve to isoproterenol generated using 30 pulses/stimulation and 20 min exposure to each agonist concentration was bell-shaped in nature, exhibiting a maximum response at 10 nM isoproterenol. Shortening the isoproterenol exposure time to 5 min for each concentration still resulted in a bell-shaped curve. Reducing the stimulus train length from 30 pulses to 10 pulses/stimulation failed to change the shape of the curve but produced a greater maximum response. However, shortening the isoproterenol exposure time to 2 min (10 pulses/stimulation) resulted in a curve which was not bell-shaped. These results suggest that prejunctional beta-adrenoceptors are susceptible to rapid desensitization upon prolonged agonist exposure and that an inverse relationship exists between stimulus train length and prejunctional beta-adrenoceptor-mediated facilitation.

Adrenergic beta-Agonists↗
PubMed1993

Is sympathetic neurotransmission in the rat mesentery modulated by prejunctional beta adrenoceptors?

The influence of prejunctional beta adrenoceptors on neurotransmitter overflow from the sympathetic nerve terminals of the normotensive rat mesentery was investigated. The mesenteric vascular bed was isolated and perfused with Krebs-bicarbonate buffer containing phentolamine (10 microM), cocaine (10 microM) and corticosterone (40 microM). Periarterial nerve stimulation (2 Hz, 120 pulses) was performed at 8-min intervals. The influence of isoproterenol (ISO) on the stimulus-induced fractional overflow of norepinephrine (S-I OFLO) was determined by generating concentration-effect curves (0.1-1000 nM, 3- or 6.5-min exposure to each concentration). ISO did not significantly increase S-I OFLO at any concentration. On the contrary, there was a decrease in S-I OFLO at the highest concentration of ISO (1 microM). The time course of the actions of ISO was studied by utilizing single concentrations of ISO (10 nM or 1 microM, 6.5-min exposure). The presence of ISO did not significantly affect S-I OFLO at either concentration. However, S-I OFLO was decreased during stimulation periods after the removal of ISO (1 microM) from the perfusate. This inhibition was significantly attenuated by propranolol (1 microM). Pretreatment with the cyclooxygenase inhibitor indomethacin (2.8 microM) had no effect on the response to ISO or the inhibition observed after ISO removal. This inhibition remained sensitive to blockade by propranolol. Salbutamol (100 nM, 6.5-min exposure), a preferential beta 2 adrenoceptor agonist, did not facilitate or inhibit S-I OFLO. These data suggest that facilitatory prejunctional beta adrenoceptors are either not present or weakly coupled to their effector system in the normotensive rat mesentery.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗
PubMed1992

Effects of immobilization stress on renal sympathetic neurotransmission.

The effects immobilization stress on renal sympathetic neurotransmission as well as on heart, spleen and adrenal catecholamine content were examined in the rat. A single 2.5 hr stress period produced significant increases in blood pressure, heart rate, plasma norepinephrine and plasma epinephrine concentrations. However, no changes in renal catecholamine content or in stimulus-induced (1 Hz, 120 pulses, supramax. V) overflow of catecholamines were observed when the isolated perfused rat kidney was studied immediately after the 2.5 hr stress period. In contrast, the single stress period produced a 3-4 fold increase in cardiac epinephrine content while no effects on spleen or adrenal catecholamine content were observed. When stress was applied for 7 daily 2.5 hr periods, the repetition of the stress failed to produce any changes in renal neurotransmitter content or stimulus-induced overflow from the isolated perfused rat kidney. The data suggest that the accumulation of epinephrine into peripheral sympathetic nerves as a result of stress-induced adrenal catecholamine release is not a phenomenon which can be generalized to all regions of the cardiovascular system.

Animals↗
PubMed1992

Chronic epinephrine treatment fails to alter prejunctional adrenoceptor modulation of sympathetic neurotransmission in the rat mesentery.

Rats were treated chronically with epinephrine (EPI-T; 100 micrograms/kg/hr, s.c.) for 6 days. On day 6 of treatment, the rats were anesthetized and the mesenteric vascular bed was isolated and perfused with Krebs' bicarbonate buffer containing cocaine (10 microM) and corticosterone (40 microM). Stimulus-induced (2 Hz, 120 pulses) overflow of neurotransmitter and its modulation by prejunctional adrenoceptors was studied. After chronic exposure to EPI, 50% of the mesenteric catecholamine stores consisted of EPI with no increase in total catecholamine content as compared to the control group (C). Absolute and fractional overflows of catecholamines upon periarterial nerve stimulation (2 Hz, 1 min) were not significantly different in the two groups. Beta adrenoceptor blockade by propranolol (10(-10) to 10(-6) M) did not alter the overflow of catecholamines. Alpha adrenoceptor blockade by phentolamine (10(-5) M) increased neurotransmitter overflow in both EPI-T and C groups. However, there was no significant difference in total catecholamine overflows between the two groups. Moreover, in the presence of phentolamine, propranolol (10(-6) M) remained without effect on overflow in both groups. These data suggest that EPI-T did not significantly increase the stimulus-induced overflow of catecholamines in the rat mesentery, nor did EPI-T result in prejunctional beta adrenoceptor modulation of neurotransmitter release in the mesenteric vascular bed.

Animals↗
PubMed1991

Effects of synthetic ANF (rANF(3-28)) on sympathetic neurotransmission in the isolated perfused rat kidney.

The effects of synthetic atrial natriuretic factor (rANF(3-28)) on sympathetic neurotransmission in the isolated perfused rat kidney was examined. ANF (10(-10)-10(-7) M) had no significant effect on stimulus-induced (1 Hz, 2 min) overflow of endogenous norepinephrine (NE) from the rat kidney. ANF also failed to affect stimulus-induced overflow which was markedly enhanced as a result of prejunctional beta-adrenoceptor activation with isoproterenol (10(-6)M). However, over the same concentration range ANF markedly attenuated the vasoconstrictor response to nerve stimulation. In addition, ANF significantly reduced the renal vasoconstrictor responses to intra-arterial injections of NE and angiotensin II. These results suggest that, while ANF potently inhibits renal sympathetic neurotransmission by inhibition of vascular responsiveness to vasoconstrictor stimuli, ANF does not appear to have a prejunctional effect to alter NE release from renal sympathetic nerves.

Animals↗
PubMed1991

Age-related changes in vascular sympathetic neurotransmission in the rat kidney.

The objective of this study was to determine the effects of aging on sympathetic neurotransmission in an important vascular resistance bed, the kidney. The experimental model utilized was the isolated perfused kidney from male Fischer 344 rats, 6, 12 and 24 months of age. Stimulus-induced (supramaximal V, 30 pulses, 1 msec) overflow of endogenous norepinephrine was examined over a wide range of frequencies (0.25-12 Hz) under three conditions: 1) control; 2) after inhibition of neuronal and extraneuronal uptake; and 3) after blockade of alpha adrenoceptors. Absolute overflow of norepinephrine was significantly greater in the 24-month group compared to the 6- and 12-month groups. Because renal catecholamine content was not significantly different between the three groups, fractional overflow also was significantly greater in the 24-month group. Despite the increase in overflow in the 24-month group, control vasoconstrictor responses to nerve stimulation were not significantly different between the three groups. Inhibition of neuronal and extraneuronal uptake did not significantly alter the relationship between fractional overflows in the three groups. In the presence of alpha adrenoceptor blockade, utilized to eliminate the influence of inhibitory prejunctional alpha adrenoceptors, fractional overflow of norepinephrine was increased in each group compared to control. However, after alpha adrenoceptor blockade, fractional overflow was not significantly different between the three age groups. In conclusion, aging results in a decrease in prejunctional alpha adrenoceptor influence and increase in norepinephrine release from renal sympathetic nerves, but not alterations in vascular response to sympathetic nerve activation.

Adrenergic alpha-Antagonists↗
PubMed1990

Effects of chronic norepinephrine administration on sympathetic neurotransmission in the isolated perfused rat kidney.

The effects of chronic NE administration (100 micrograms/kg/hr s.c., 6 days) on the stimulus-induced overflow of neurotransmitter from the isolated perfused rat kidney were examined. This treatment increased renal NE content and increased the absolute stimulus-induced overflow of NE. The increase in absolute overflow was not simply the result of the increase in renal NE content as fractional overflow was also increased slightly (20%). Alpha adrenoceptor blockade with phentolamine eliminated the NE treatment-induced difference in fractional overflow. However, the dose-response curves to phentolamine and the alpha-2 adrenoceptor agonist UK 14,304 on stimulus-induced overflow from the kidney were not significantly different after NE treatment. Chronic EPI treatment (same dose) produced an 80% increase in fractional stimulus-induced overflow of neurotransmitter but the dose-response curve to UK 14,304 was shifted only slight to the right (3-fold) of the control curve. No influence of prejunctional beta adrenoceptors on stimulus-induced overflow was observed in either the control of the NE-treated group. In conclusion, the data regarding fractional overflow and the effects of the phentolamine suggest that NE treatment produces minimal change whereas EPI treatment produces marked decreases in the influence in prejunctional alpha adrenoceptors. However, although the data with UK 14,304 after NE treatment support this conclusion, the failure of EPI treatment to alter the dose-response curve to UK 14,304 does not. The apparent contradiction of the results with the alpha adrenoceptor agonist in the EPI-treated group as well as the large differences between the effects of NE vs. EPI treatment on stimulus-induced overflow and prejunctional alpha adrenoceptor function cannot be explained at this time.

Adrenergic alpha-Agonists↗
PubMed1989

Acute epinephrine treatment fails to facilitate stimulus-induced neurotransmitter overflow in the isolated perfused rat kidney.

The effects of acute in vitro epinephrine treatment (40 nM, 1 hr) on stimulus-induced neurotransmitter overflow from the isolated perfused kidney were examined. This treatment resulted in the release of both norepinephrine and epinephrine upon nerve stimulation but no increase in fractional stimulus-induced overflow. Experiments utilizing beta and/or alpha adrenoceptor blockade revealed that beta adrenoreceptor blockade alone had no effect on overflow but that a dose-dependent decrease in stimulus-induced overflow was produced by beta adrenoceptor blockade after alpha adrenoceptor blockade. Thus, under normal conditions the facilitatory influence of epinephrine via prejunctional beta adrenoceptors is masked by the prejunctional alpha adrenoceptor negative feedback loop. The effects of extraneuronal presentation of isoproterenol, salbutamol and epinephrine on stimulus-induced neurotransmitter overflow also were examined. In the absence of alpha adrenoceptor blockade, only epinephrine failed to enhance neurotransmitter overflow. After competitive alpha adrenoceptor blockade, all three agents produced significant increases in stimulus-induced neurotransmitter overflow from the rat kidney, although alpha adrenoceptor stimulation appeared to limit this effect at high agonist concentrations. We conclude that the dominance of prejunctional alpha adrenoceptors in the rat kidney results in the inability of epinephrine to produce beta adrenoceptor-mediated facilitation of neurotransmitter overflow even when it is incorporated into renal neurotransmitter stores and coreleased with endogenous norepinephrine upon nerve stimulation.

Animals↗
PubMed1988

Enhanced endogenous neurotransmitter overflow in the isolated perfused rat kidney after chronic epinephrine administration: lack of a prejunctional beta adrenoceptor influence.

This study examines stimulus-induced overflow of endogenous catecholamines from the isolated perfused kidney of rats after epinephrine (EPI) administration at 100 micrograms/kg/hr for 6 days via s.c. implanted osmotic minipumps. This regimen resulted in the incorporation of EPI into renal catecholamine stores and the co-release of EPI with norepinephrine during periarterial nerve stimulation. Stimulus-induced (1 Hz) absolute and fractional overflows of neurotransmitter were significantly greater in the EPI-treated rats. These differences in overflow were not altered by uptake blockade. Alpha adrenoceptor blockade with phentolamine (10(-9)-10(-5) alone increased overflow in a dose-dependent manner in both groups, although to a greater extent in the EPI-treated group. However, in the presence of 1 microM propranolol the effect of phentolamine in the EPI-treated group was greatly reduced such that, in the presence of propranolol, phentolamine was less effective in the EPI-treated vs. vehicle-treated rats. Beta adrenoceptor blockade alone with propranolol (10(-9)-10(-6) M) did not alter stimulus-induced overflow in either group but propranolol dose dependently reduced fractional overflow in the EPI-treated rats when the experiments were done in the presence of 10 microM phentolamine. It is concluded that the enhanced fractional overflow observed in the kidneys of EPI-treated rats was not due to beta adrenoceptor activation, but rather, a reduced influence of the prejunctional alpha adrenoceptor-mediated negative feedback loop. Beta adrenoceptor activation by neurally released EPI does not appear to modulate stimulus-induced overflow unless the dominant inhibitory alpha adrenoceptor mechanism is inactivated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Cardiovascular responsiveness to sympathetic activation after chronic epinephrine administration.

The effects of chronic elevation of plasma epinephrine concentrations on pressor and cardiac chronotropic responses to spinal stimulation and exogenous norepinephrine were studied in the pithed rat. Animals were treated s.c. with epinephrine (100 micrograms/kg/hr) or vehicle for 6 days. Treatment with epinephrine resulted in hypertension. Epinephrine treatment significantly reduced pressor and cardiac chronotropic responses to norepinephrine. This treatment also reduced cardiac chronotropic responses to spinal stimulation but had no significant effect on pressor responses to spinal stimulation. The preferential beta-2 adrenoceptor antagonist ICI 118,551 (50 micrograms/kg) had no effect on pressor or cardiac chronotropic responses to norepinephrine in either vehicle-treated or epinephrine-treated animals. Similarly, pressor responses to spinal stimulation were unaffected in the vehicle-treated group. However, ICI 118,551 significantly reduced pressor responses to spinal stimulation after epinephrine treatment. Chronic epinephrine treatment also resulted in accumulation of epinephrine in the heart, kidneys and aorta. However, epinephrine accumulation in the heart was much greater than in the kidney or aorta. Acute infusion of epinephrine, which produced plasma epinephrine concentrations similar to those observed in the chronically treated animals, caused a reduction of pressor and cardiac chronotropic responses to both nerve stimulation and norepinephrine. In conclusion, chronic epinephrine treatment led to accumulation of epinephrine in peripheral tissues and to the development of a facilitatory influence of beta-2 adrenoceptors on pressor responses to nerve stimulation in the pithed rat that were not observed in vehicle-treated animals. The authors believe that this influence is prejunctional in nature.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1986

Enhanced stimulus-induced neurotransmitter overflow in epinephrine-induced hypertensive rats is not mediated by prejunctional beta-adrenoceptor activation.

The present study examines the effect of 6-day epinephrine treatment (100 micrograms/kg per h, s.c.) on stimulus-induced (1 Hz) endogenous neurotransmitter overflow from the isolated perfused kidney of vehicle- and epinephrine-treated rats. Renal catecholamine stores and stimulus-induced overflow in the vehicle-treated group consisted of norepinephrine only. However, epinephrine treatment resulted in the incorporation of epinephrine into renal catecholamine stores such that approximately 40% of the catecholamine present was epinephrine while the norepinephrine content was reduced by a similar degree. Total tissue catecholamine content of the kidney on a molar basis was unchanged. Stimulus-induced fractional overflow of neurotransmitter from the epinephrine-treated kidneys was approximately twice normal and consisted of both norepinephrine and epinephrine in proportions similar to those found in the kidney. This difference in fractional overflow between groups was not affected by neuronal and extraneuronal uptake blockade. Propranolol had no effect on stimulus-induced overflow in either group. Phentolamine increased stimulus-induced overflow in both groups although the increment in overflow was greater in the epinephrine-treated group. In conclusion, chronic epinephrine treatment results in enhanced fractional neurotransmitter overflow. However, neither alterations in prejunctional beta-adrenoceptor influences nor alterations in neuronal and extraneuronal uptake mechanisms appear to be responsible for this alteration. Furthermore, data obtained with phentolamine alone do not suggest alpha-adrenoceptor desensitization as the cause of the enhanced neurotransmitter overflow after epinephrine treatment.

Animals↗
PubMed1985

Influence of felodipine and verapamil on the sympathetic transmitter release and on the pre- and post-junctional effects of exogenous noradrenaline in the perfused rat kidney.

The effects of various concentrations (0.01 to 10 mumol/L) of felodipine and verapamil on the peripheral sympathetic function were studied in perfused rat kidney preparations in vitro. Neither of these agents inhibited stimulus-induced 3H-noradrenaline (norepinephrine) release (at 0.5 and 2.0 Hz). Higher concentrations of felodipine (10 mumol/L) and verapamil (1 and 10 mumol/L) significantly potentiated the transmitter release at both frequencies of stimulation. Unlike phentolamine, felodipine 10 mumol/L enhanced the ability of exogenous noradrenaline to inhibit 3H-noradrenaline-release, indicating that this vasodilator did not antagonise prejunctional alpha 2-receptors. The effects of verapamil 1 mumol/L were similar to that of felodipine in this respect; however, verapamil in higher concentrations (10 mumol/L) produced slight but significant attenuation of exogenous noradrenaline-induced inhibition of the transmitter release. Both felodipine and verapamil produced concentration-dependent inhibition of the vasoconstrictor responses to exogenous noradrenaline. It is concluded from these studies that the effects of these agents on the transmitter release may not have any clinical significance, but their ability to attenuate vascular effects of noradrenaline could contribute to their antihypertensive properties.

Animals↗