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H Majewski

Publications and source records attributed to H Majewski.

At least 19 recordsLinked to original sources
PubMed1992

An inhibitory effect of isoprenaline on stimulation-induced noradrenaline release from rat atria.

Isoprenaline (0.1 microM), in the presence of phentolamine (1 microM) to block autoinhibitory alpha-adrenoceptors, significantly increased the efflux of radioactivity produced by field stimulation (2 Hz for 60 s) from rat isolated atria in which the noradrenergic transmitter stores had been labelled with [3H]noradrenaline. This facilitatory effect of isoprenaline on noradrenergic transmission was not affected by the selective beta 1-adrenoceptor antagonist CGP 20712A (0.3 microM). However, the selective beta 2-adrenoceptor antagonist ICI 118551 (0.1 microM) not only abolished the facilitatory effect of isoprenaline but reversed it to an inhibitory effect, indicating that the prejunctional beta-adrenoceptors subserving facilitation of noradrenergic transmission in rat atria are of the beta 2-subtype. The inhibitory effect of isoprenaline that was revealed by blockade of beta 2-adrenoceptors was abolished by atenolol (3 microM) in a concentration which markedly reduced the effect of isoprenaline on the rate of atrial beating. This finding suggests that activation of beta 1-adrenoceptors on atrial myocytes by isoprenaline may have resulted in release of one or more substance(s) which inhibited stimulation-induced release of noradrenaline, presumably by activating prejunctional receptors. The inhibitory effect of isoprenaline on noradrenergic transmission was not affected by the prostaglandin synthesis inhibitor indomethacin (10 microM) suggesting that prostaglandins were not involved.

Adrenergic alpha-Antagonists↗
PubMed1992

Enalapril decreases plasma noradrenaline levels during the cold pressor test in human hypertensives.

1. The effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on the responses of blood pressure and plasma catecholamine levels to the cold pressor test in human hypertensives were examined. 2. Systolic and diastolic blood pressure decreased significantly after treatment with enalapril (5 mg/day for 4 weeks) as did the resting level of plasma noradrenaline. 3. The cold pressor test induced a rise in blood pressure and plasma noradrenaline levels. After 2 and 4 weeks enalapril treatment, the rises in the plasma noradrenaline level and systolic and diastolic pressure due to cold pressor test were reduced significantly. 4. These results suggest that ACE inhibition has a sympatho-inhibitory effect. One possible explanation is that enalapril reduces angiotensin II formation thus decreasing the activation of release-enhancing angiotensin II receptors on postganglionic sympathetic nerve endings.

Blood Pressure↗
PubMed1992

Prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are sensitive to N-ethylmaleimide, but not pertussis toxin.

1. The identity of the G-proteins involved in prejunctional alpha 2-adrenoceptor signal transduction in mouse atria was examined by use of the G-protein inactivators N-ethylmaleimide and pertussis toxin. 2. The alpha 2-adrenoceptor partial agonist clonidine (0.03 microM) inhibited the electrical stimulation-induced (S-I) outflow of radioactivity from mouse atria which were incubated with [3H]-noradrenaline and stimulated at 5 Hz. The partial alpha 2-adrenoceptor agonist St 363 (10 microM) inhibited the S-I outflow of radioactivity at the lower stimulation frequency of 2.5 Hz. The inhibitory effects of these compounds were not altered in mice pretreated with pertussis toxin (1.5 micrograms, i.v.). 3. The alpha 2-adrenoceptor antagonist, idazoxan (0.1 microM), increased the S-I outflow of radioactivity from mouse atria stimulated at 5 Hz, and this effect was not altered in atria from mice pretreated with pertussis toxin. 4. The inhibitory effects of clonidine and St 363 and the facilitatory effect of idazoxan on the S-I outflow of radioactivity from mouse atria were significantly less in atria incubated with N-ethylmaleimide (NEM, 3 microM) for 60 min before the [3H]-noradrenaline incubation. 5. The results suggest that prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are NEM-sensitive, but pertussis toxin insensitive.

Adrenergic alpha-Agonists↗
PubMed1992

Influence of papaverine on rat bladder contractions in vivo.

In an acute rat model (in vivo) spontaneous rhythmic bladder contractions were induced by ligation of the urethra. In addition single bladder contractions were recorded during neurostimulation of the pelvic nerve. Spontaneous and electrically induced bladder contractions were sensitive to papaverine and isoprenaline in vivo. The basal bladder pressure and bladder contraction parameters were reduced more potently by isoprenaline. Blood pressure decreased significantly after isoprenaline injection (0.5-50 micrograms/kg = 4.73 x 10(-6)-4.73 x 10(-4) mol/l) and high concentration of papaverine (5 mg/kg = 2.95 x 10(-2) mol/l). Compared to isoprenaline papaverine was less toxic. These results are different to previous in vitro investigations in rat bladder strips. In vivo papaverine seems to be less effective on nerve-mediated bladder contractions and decreases bladder pressure. Our results indicate that beta-adrenergic receptors play a potent role in the inhibition of spontaneous and pelvic nerve-induced bladder contraction.

Animals↗
PubMed1991

Milrinone inhibits sympathetic-mediated tachycardia by a postjunctional action independent of cyclic AMP.

In pithed rats with stimulated sympathetic outflow, the phosphodiesterase inhibitor milrinone (0.3 mg/kg, i.v.) decreased the peak tachycardiac response produced by both sympathetic nerve stimulation (15 s at 0.5-3 Hz) and norepinephrine administration (0.3-5 micrograms/kg, i.v.). However, another phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 0.5 mg/kg, i.v.) had no effect on the peak tachycardic response to sympathetic stimulation. Similarly, in isolated rat atria, milrinone (9 mumol/L) inhibited the tachycardia produced by norepinephrine, whereas IBMX (1 mumol/L) had no effect. The inhibitory effect of milrinone on sympathetic responses was not due to changes in norepinephrine release since milrinone (9 mumol/L) increased norepinephrine release in isolated rat atria incubated with [3H]norepinephrine. When the duration of the tachycardia (rather than the peak tachycardic response) produced by sympathetic nerve stimulation was measured, it was found to be prolonged by both milrinone and IBMX, suggesting that in this case cyclic AMP was involved. Furthermore, in contrast to its inhibitory effects on norepinephrine-induced tachycardia in rat atria, milrinone enhanced the tachycardia produced by the adenylate cyclase activator forskolin. These results suggest that milrinone has complex actions on sympathetic control of heart rate and that beta-adrenoceptor tachycardia occurs by mechanisms dependent on and independent of cyclic AMP.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Evidence that angiotensin II enhances noradrenaline release from sympathetic nerves in mouse atria by activating protein kinase C.

1. Mouse atria were incubated with [3H]-noradrenaline and the outflow of radioactivity induced by electrical field stimulation (5 Hz, 60 s) was used as an index of noradrenaline release. Angiotensin II (1 x 10(-8) M) significantly enhanced the stimulation-induced (S-I) outflow of radioactivity. 2. Phorbol 12-myristate 13-acetate (0.001-1.0 x 10(-6) M) and phorbol 12, 13-dibutyrate (0.001-1.0 x 10(-6) M), protein kinase C activating phorbol esters, significantly enhanced the S-I outflow of radioactivity. Phorbol dibutyrate produced a greater maximal enhancement of S-I outflow of radioactivity than phorbol myristate acetate. The enhancement of S-I outflow of radioactivity produced by the combination of phorbol dibutyrate (1.0 x 10(-7) M) and phorbol myristate acetate (1.0 x 10(-7) M) was no greater than that produced by phorbol dibutyrate (1.0 x 10(-7) M) alone. The enhancement of S-I outflow of radioactivity produced by phorbol myristate acetate (1.0 x 10(-7) M) was constant whether the tissue was exposed for 15, 45 or 75 min. 3. When angiotensin II (1.0 x 10(-8) M) was present with the maximally effective concentration of phorbol dibutyrate (1.0 x 10(-7) M) it did not increase S-I outflow of radioactivity. 8-bromo-cyclic AMP (9.0 x 10(-5) M) by itself increased the S-I outflow of radioactivity and in the presence of the maximally effective concentration of phorbol dibutyrate the enhancement of S-I outflow of radioactivity produced by 8-bromo-cyclic AMP was maintained. 4. A protein kinase inhibitor, K-252a (1.0 x 10(-6) M), did not affect S-I outflow of radioactivity. K-252a significantly reduced the enhancement of S-I outflow of radioactivity produced by both phorbol myristate acetate (0.03 or 0.1 x 10(-6) M) and phorbol dibutyrate (0.01 or 1.0 x 10(-6) M). 5. K-252a (1.0 x 10(-6) M) blocked the enhancement of S-I outflow of radioactivity produced by angiotensin II (1.0 x 10(-8) M) and tetraethylammonium (1.0 x 10(-4) M). 6. These results suggest that angiotensin II receptors may enhance noradrenaline release through the pool of protein kinase C that is activated by phorbol dibutyrate.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Evidence for facilitatory and inhibitory muscarinic receptors on postganglionic sympathetic nerves in mouse isolated atria.

1. McNeil A 343 (10 microM-30 microM) enhanced the fractional stimulation-induced (S-I) outflow of radioactivity from mouse isolated atria which had been incubated with [3H]-noradrenaline. The enhancing effect of McNeil A 343 was not altered by hexamethonium (300 microM) suggesting that it was not due to an action at nicotinic receptors. It is also unlikely that McNeil A 343 enhanced the S-I outflow of radioactivity in mouse atria by blocking neuronal reuptake of noradrenaline since the effect persisted in the presence of cocaine (30 microM). 2. The facilitatory effect of McNeil A 343 on the S-I outflow of radioactivity was attenuated by atropine (0.3 microM), pirenzepine (0.2 microM or 1.0 microM), dicyclomine (1.0 microM) and methoctramine (1.0 microM) and was thus due to activation of muscarinic receptors. 3. In contrast to the effect of McNeil A 343, another muscarinic receptor agonist, carbachol (3.0 microM) significantly decreased the S-I outflow of radioactivity. The receptors through which McNeil A 343 acts to enhance the S-I outflow of radioactivity appear to be distinct from inhibitory prejunctional muscarinic receptors. The relatively M 1-selective antagonist, pirenzepine (0.2 microM), attenuated the facilitatory effect of McNeil A 343 whereas a higher concentration (1.0 microM) was required to block the inhibitory effect of carbachol. Conversely, the relatively M2-selective antagonist, methoctramine (0.1 microM), blocked the inhibitory effect of carbachol but a higher concentration of methoctramine (1.0 microM) was required to block the facilitatory effects of McNeil A 343. These results tentatively ascribe facilitatory muscarinic receptors as belonging to the Ml subtype and inhibitory muscarinic receptors as belonging to the M2 subtype. 4. The non-selective muscarinic receptor antagonist, atropine, enhanced the S-I outflow of radioactivity, suggesting that there was tonic activation of inhibitory prejunctional muscarinic receptors by endogenous acetylcholine released from parasympathetic nerves. However, pirenzepine (0.03 pM-LO microM) did not decrease the S-I outflow of radioactivity, suggesting that under the conditions of the present study, facilitatory muscarinic receptors are not tonically activated by endogenous acetylcholine.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1990

Pertussis toxin differentiates between alpha 1- and alpha 2-adrenoceptor-mediated inhibition of noradrenaline release from rat kidney cortex.

In slices of rat kidney cortex incubated in [3H]noradrenaline, the alpha 1-adrenoceptor agonist methoxamine (10 microM), the alpha 2-adrenoceptor agonist clonidine (0.1 microM), as well as adenosine (10 microM), inhibited the electrical stimulation-induced (S-I) outflow of radioactivity, at a stimulation frequency of 1 Hz. Prior treatment of rats with pertussis toxin (25 micrograms/kg i.v.), which abolished the negative inotropic effect of carbachol (10 microM) on isolated atria, prevented the inhibition caused by methoxamine, but not that caused by clonidine or adenosine. At a stimulation frequency of 5 Hz, the alpha 2-adrenoceptor antagonist idazoxan (0.1 microM) and the prostaglandin synthesis inhibitor indomethacin (10 microM) both facilitated the S-I outflow of radioactivity, and neither of these effects were altered by pertussis toxin. These results suggest that a pertussis toxin sensitive G-protein is involved in alpha 1-adrenoceptor inhibition of noradrenaline release, but not in alpha 2-adrenoceptor, adenosine or prostaglandin inhibition.

Animals↗
PubMed1990

Inhibitory prejunctional muscarinic receptors at sympathetic nerves do not operate through a cyclic AMP dependent pathway.

In mouse atria previously incubated with [3H]-noradrenaline, carbachol (1.0 mumo1/l) significantly inhibited the fractional stimulation-induced (S-I) outflow of radioactivity. The inhibitory effect of carbachol was greater in the presence of the alpha-adrenoceptor antagonist phentolamine (1.0 mumol/l), which by itself significantly increased the S-I outflow of radioactivity. In both cases the inhibitory effect of carbachol was blocked by atropine (0.3 mumol/l), suggesting that the effect was mediated through muscarinic receptors. 8-Bromo cyclic AMP (270 mumol/l) in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX, 100 mumol/l), was used to maximally enhance the S-I outflow of radioactivity through the cyclic AMP mechanism. The inhibitory effect of carbachol either in the presence or in the absence of phentolamine, was not reduced in the presence of 8-bromo cyclic AMP and IBMX. Similar results with carbachol in the presence of 8-bromo cyclic AMP and IBMX were also found in rat right atrial strips which had been incubated with [3H]-noradrenaline. These results suggest that the effects through inhibitory prejunctional muscarinic receptors are not mediated by cyclic AMP. The protein kinase inhibitor, staurosporine (0.1 mumol/l), significantly blocked the enhancing effects of 8-bromo cyclic AMP (270 mumol/l) plus IBMX (100 mumol/l) on the S-I outflow of radioactivity from rat atrial strips. The inhibitory effect of carbachol (1.0 mumol/l) however, was not reduced in the presence of staurosporine, suggesting that protein kinases affected by staurosporine (protein kinase A, protein kinase C) are not involved in the post-receptor mechanism for inhibitory prejunctional muscarinic receptors. This finding further rules out the involvement of cyclic AMP in muscarinic inhibition. The inhibitory effect of carbachol either by itself or in the presence of phentolamine, was not reduced in atria from mice that had been pretreated with pertussis toxin (1.5 or 3.0 micrograms). Furthermore, in rat atrial strips, the inhibitory effect of carbachol either in the presence or in the absence of phentolamine, was also not altered by pretreating the rats with pertussis toxin (8.4 micrograms). The results suggest that in both tissues the major mechanism for inhibition of noradrenaline release through muscarinic receptors does not involve a pertussis toxin sensitive G protein.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Inhibition of noradrenaline release by neuropeptide Y does not involve protein kinase C in mouse atria.

In this study, we investigated the possible involvement of protein kinase C in the inhibitory effect of neuropeptide Y (NPY) on the electrical stimulation-induced release of radioactivity from mouse atria incubated with [3H]-noradrenaline. The protein kinase C activators, phorbol dibutyrate (PDB, 0.001-1 mumol/l) and phorbol myristate acetate (PMA, 0.001-1 mumol/l), increased the release of noradrenaline in a concentration-dependent manner. Interestingly, the maximum effect on noradrenaline release was significantly greater for phorbol dibutyrate compared to phorbol myristate acetate. The enhancement produced by both phorbol esters was significantly reduced by the protein kinase C inhibitor, K-252a (1 mumol/l). In the presence of the concentration of either phorbol ester (PMA, 0.1 mumol/l, PDB 1 mumol/l), that was supramaximal for increasing the release of noradrenaline, NPY (0.3 mumol/l) significantly inhibited the release of noradrenaline. Moreover, in the presence of the protein kinase C inhibitors, K-252a (1 mumol/l) or polymyxin B (70 mumol/l), NPY (0.3 mumol/l) also significantly inhibited the release of noradrenaline. Therefore, it is concluded that protein kinase C is not involved in the prejunctional inhibitory effect of NPY on noradrenaline release in the mouse atria. Furthermore, since K-252a also inhibits cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase and myosin light chain kinase, it is likely that these kinases are also not involved in the inhibitory mechanism of NPY.

Animals↗
PubMed1990

Prejunctional beta-adrenoceptors, angiotensin II and neuropeptide Y receptors on sympathetic nerves in mouse atria are linked to N-ethylmaleimide-susceptible G-proteins.

We used the alkylating agent N-ethylmaleimide in order to investigate G-proteins linked to release-modulating prejunctional receptors of sympathetic nerves in mouse atria incubated with [3H]-noradrenaline. The receptors tested were facilitatory beta-adrenoceptors and angiotensin II receptors and inhibitory neuropeptide Y receptors. In order to evaluate the specificity of the N-ethylmaleimide treatment, we tested N-ethylmaleimide against the second messenger pathways that are linked to beta-adrenoceptors (adenylate cyclase) and angiotensin II (protein kinase C). The results show that a 60-min preincubation with N-ethylmaleimide (3 microM) abolished the facilitatory effect of isoprenaline (0.1 microM) and angiotensin II (0.1 microM) on the stimulation-induced release of noradrenaline and reduced the inhibitory action of neuropeptide Y (0.3 microM). N-ethylmaleimide had no effect on the stimulatory action of either phorbol dibutyrate (0.01, 0.1 microM), forskolin (10 microM), or a combination of 8-bromo adenosine-3'5'-monophosphate (90 microM) and 3-isobutyl-1-methylxanthine (100 microM). However, at a higher concentration (10 microM), N-ethylmaleimide reduced the facilitatory effect of phorbol dibutyrate (0.1 microM) and the combination of 8-bromo adenosine-3',5'-monophosphate (90 microM) and 3-isobutyl-1-methylxanthine (100 microM). This suggests that N-ethylmaleimide at 3 microM but not 10 microM was selective for receptor-mediated modulation of noradrenaline release without directly affecting the adenylate cyclase (forskolin, 8-bromo adenosine-3',5'-monophosphate + 3-isobutyl-1-methylxanthine) or protein kinase C (phorbol dibutyrate) transduction pathways. In atria from mice pretreated with pertussis toxin (1.5 micrograms/mouse), N-ethylmaleimide preincubation (1 and 3 microM) resulted in a more pronounced reduction of the inhibitory action of neuropeptide Y (0.3 microM). The nature of this interaction is unclear. Since N-ethylmaleimide has been shown in other studies to inactivate G-proteins, the inhibitory effect of N-ethylmaleimide on prejunctional beta-adrenoceptors, angiotensin II receptors and neuropeptide Y receptors of sympathetic nerves may suggest that G-proteins are involved with these receptors, although other effects of N-ethylmaleimide on the receptor coupling processes cannot be ruled out. Moreover, it appears that the concentration of N-ethylmaleimide used is critical since a higher concentration (10 microM) resulted in non-specific effects on signal transduction mechanisms in the present experimental conditions.

Adenylate Cyclase Toxin↗
PubMed1990

Pertussis toxin attenuates angiotensin II but not beta-adrenoceptor facilitation of noradrenaline release from rat kidney cortex.

1. Angiotensin II (AII; 0.01 and 0.1 mumols/L), angiotensin I (AI, 0.1 mumols/L) and the beta-adrenoceptor agonist isoprenaline (0.1 mumols/L) all facilitated the stimulation-induced outflow of radioactivity from slices of rat kidney cortex incubated in [3H]-noradrenaline. 2. Treatment of rats with pertussis toxin (25 and 50 micrograms/kg i.v.) to inactivate G-proteins attenuated the facilitation caused by AII and AI, but not that caused by isoprenaline. 3. The hypothesis that isoprenaline enhances noradrenaline release by generating AII to activate facilitatory prejunctional AII receptors is not supported by the present study. The hypothesis predicts that pertussis toxin, by inactivating the G-proteins associated with AII receptors, should have inhibited the facilitatory effect of isoprenaline. This did not occur.

Angiotensin I↗
PubMed1989

Modulation of noradrenaline release in slices of rat kidney cortex through alpha 1- and alpha 2-adrenoceptors.

Slices of rat kidney cortex were incubated in [3H]noradrenaline, then placed in a flow cell and subjected to electrical field stimulation. At a stimulation frequency of 5 Hz, both the alpha 2-adrenoceptor antagonist idazoxan (0.1 microM) and the alpha 1-adrenoceptor antagonist prazosin (0.1 microM) significantly enhanced the stimulation-induced (S-I) outflow of radioactivity from the slice. However, neither clonidine (0.1 microM) nor methoxamine (10 microM), alpha 2- and alpha 1-agonists respectively, affected the S-I outflow of radioactivity at this stimulation frequency. At a lower stimulation frequency (1 Hz), the S-I outflow of radioactivity was not affected by idazoxan or prazosin, but was inhibited by both clonidine and methoxamine. The effect of clonidine was prevented by idazoxan (0.1 microM), but not by prazosin (0.1 microM). The effect of methoxamine was abolished by prazosin (0.1 microM), but not by idazoxan (0.1 microM). The inhibitory effect of methoxamine was not prevented by the prostaglandin synthesis inhibitor indomethacin (10 microM) or the adenosine receptor antagonist 8-phenyltheophylline (1 microM) and thus was not mediated by either prostaglandins or adenosine. The results suggest that both prejunctional alpha 1- and alpha 2-adrenoceptors are directly involved in modulation of noradrenaline release from the renal sympathetic nerves of the rat.

Animals↗
PubMed1989

Inhibition of noradrenaline release by neuropeptide Y in mouse atria does not involve inhibition of adenylate cyclase or a pertussis toxin-susceptible G protein.

Neuropeptide Y (30-1000 nmol/l) significantly inhibited the fractional stimulation-induced outflow of radioactivity from mouse atria preincubated with [3H]-noradrenaline. The inhibitory effect of neuropeptide Y was observed at all frequencies tested (2, 5 and 10 Hz) as well as after alpha-adrenoceptor blockade with phentolamine (1 mumol/l). A combination of 8-bromo adenosine cyclic-3'-5'-monophosphate (90 or 270 mumol/l) with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (100 mumol/l) was used to saturate maximally the adenylate cyclase system and these drug combinations significantly enhanced the stimulation-induced outflow of radioactivity. However, neuropeptide Y inhibited the stimulation-induced outflow in the presence of these drugs, suggesting that the inhibitory effect of neuropeptide Y was not due to decreasing endogenous cyclic AMP formation. Finally, atria from mice treated with pertussis toxin were used. In this case, the inhibitory effect of neuropeptide Y on the stimulation-induced outflow of radioactivity was still observed suggesting that inhibitory prejunctional neuropeptide Y receptors are not coupled to a pertussis toxin-susceptible G protein.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Beta-adrenoceptor blockade and sympathetic neurotransmission in the pithed rat.

The effects of the beta 1-adrenoceptor blocking drug atenolol and the beta 2-adrenoceptor blocking drug ICI 118551 (ICI, Melbourne, Australia) on noradrenaline release and blood pressure were investigated using the pithed rat, which was subjected to continuous electrical stimulation of the spinal sympathetic outflow (pulses at 3 Hz). This stimulation increased blood pressure but not heart rate. The noradrenaline release rate was calculated by infusing [3H] noradrenaline and measuring the steady-state concentrations of both endogenous and infused noradrenaline. Atenolol (0.2 mg/kg bolus plus 0.1 mg/kg per h, intra-arterially) had no effect on the noradrenaline release rate or heart rate, but significantly decreased blood pressure. On the other hand, ICI 118551 (0.2 mg/kg bolus plus 0.1 mg/kg per h. intra-arterially) had no significant effect on blood pressure or heart rate, but did inhibit the noradrenaline release rate. The sympathoinhibitory effect of ICI 118551 was not observed in animals which had been adrenal medullectomized, suggesting that its effect on noradrenaline release was due to blockade of activation of facilitatory prejunctional beta 2-adrenoceptors by adrenaline. The reduced noradrenaline release in the presence of ICI 118551 was not accompanied by a reduction in blood pressure. This may be because ICI 118551 also blocked vasodilatory beta 2-adrenoceptors on vascular smooth muscle. Indeed, in unstimulated pithed rats, infusions of adrenaline which were non-pressor were found to be pressor after ICI 118551 was administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1989

Angiotensin II and noradrenergic transmission in the pithed rat.

The norepinephrine (NE) release rate, determined in the pithed rat with stimulated sympathetic outflow (3 Hz), was calculated from the steady-state concentrations of endogenous NE and [3H]NE in the central venous pool after infusion of [3H]NE intraarterially (i.a.). This technique appropriately corrects for NE metabolism and disposition since the [3H]NE closely follows the removal path of neuronally released NE. Infusion of angiotensin II (AII) [0.1 microgram/kg/min, intravenously (i.v.)] failed to increase the NE release rate. A higher rate of infusion of AII (1.0 microgram/kg/min, i.v.) markedly increased the NE release rate. The converting enzyme inhibitor captopril (1 mg/kg, i.v.) and the AII-receptor blocking drug saralasin (10 micrograms/kg/min, i.v.) decreased the NE release rate, indicating a tonic activation of facilitatory prejunctional AII receptors at sympathetic nerve endings. After bilateral nephrectomy, captopril and saralasin did not decrease the NE release rate. This suggests that renin release from the kidney is the primary determinant of AII effects and that local tissue generation of AII is not important Other differences were observed in nephrectomized rats: AII (0.1 microgram/kg/min, i.v.), in contrast to its lack of effect in rats with kidneys, increased the NE release rate. This suggests that the lack of effect of AII (0.1 microgram/kg/min, i.v.) on NE release in rats with kidneys may occur because facilitatory prejunctional AII receptors are maximally activated by endogenous AII.

Angiotensin II↗