Effect of catecholamine-receptor stimulating agents on blood pressure after local application in the nucleus tractus solitarii of the medulla oblongata

doi:10.1016/0014-2999(79)90146-8

European Journal of Pharmacology

Volume 55, Issue 1, 1 April 1979, Pages 43-56

https://doi.org/10.1016/0014-2999(79)90146-8 Get rights and content

Abstract

The effect of various catecholamines and α-mimetics, given by microinjection in the A₂-region of the nucleus tractus solitarii (NTS), on blood pressure was investigated in anesthetizedmale rats. A dose-dependent decrease of blood pressure and heart rate was induced by adrenaline as the most effective drug, followed by noradrenaline, dopamine, α-methylnoradrenaline and octopamine. Ablation of the rostral or caudal part of the NTS, or removal of the area postrema did not diminish the effect of α-methylnoradrenaline. Higher doses of noradrenaline and α-methylnoradrenaline caused an initial rise of blood pressure, while theblood pressure lowering effect of noradrenaline was diminished, and that of α-methylnoradrenaline and dopamine delayed. Isoprenaline and the (+)-stereoisomers of noradrenaline and α-methylnoradrenaline were ineffective. The hypotensive effect of dopamine was not prevented by systemic injection of the dopamine β-hydroxylase inhibitor FLA 63. Prior application of haloperidol, yohimbine and phentolamine antagonized the hypotensive response to dopamine and α-methylnoradrenaline. Application of peripherally effective α-mimetics into the A₂-region had no or little effect, while high doses increased blood pressure. Tyramine and clonidine caused some decrease of blood pressure. Clonidine also decreased blood pressure when it was applied in the area of the locus coeruleus. Application of isoprenaline in the locus coeruleus also decreased blood pressure while in contrast adrenaline, noradrenaline, dopamine and α-methylnoradrenaline increased blood pressure. The present data suggest that the catecholaminergic receptors in the A₂-region of the NTS differ from the classic vascular α-receptor and that the NTS also may contain structures which can antagonize the decrease in blood pressure.

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L-DOPA inhibits excitatory synaptic transmission in the rat nucleus tractus solitarius through release of dopamine
2017, Neuroscience
Citation Excerpt :
Several lines of evidence also suggest that dopamine is another transmitter. For instance, dopamine is presented in the afferent fibers (Finley and Katz, 1992) and microinjection of dopamine into the NTS produces either hypertension with tachycardia (Granata and Woodruff, 1982) or hypotension with bradycardia (Zandberg et al., 1979). D2 receptors and/or their mRNA have been found in the vagal afferent neurons (Lawrence et al., 1995) and in the NTS (Huey and Powell, 2000), while D1 receptors have not been yet (Qian et al., 1997).
The mode of action of L-DOPA on excitatory synaptic transmission in second-order neurons of the nucleus tractus solitarius (NTS) was studied using the rat brainstem slices. Superfusion of L-DOPA (10 μM) reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) without any effect on the amplitude. A low concentration (1 μM) was ineffective on the mEPSCs, and the highest concentration (100 μM) exerted a stronger inhibitory effect. L-DOPA (10 μM) decreased the amplitude of EPSCs (eEPSCs) evoked by electrical stimulation of the tractus solitarius and increased the paired-pulse ratio. The inhibitory effects of L-DOPA on mEPSCs and eEPSCs were similar to those of dopamine (100 μM). The effects of L-DOPA were blocked by a competitive antagonist, L-DOPA methyl ester (100 μM) and also by a D₂ receptor antagonist, sulpiride (10 μM), while those of dopamine were blocked by the latter but not by the former. In reserpine (5 mg/kg, s.c.)-treated rats, the effects of L-DOPA on both mEPSCs and eEPSCs were completely abolished, but those of dopamine remained unchanged. The present results suggest a possibility that L-DOPA may induce the release of dopamine from the axon terminals in the NTS and the released dopamine suppresses the glutamatergic transmission through activation of the presynaptic D₂ receptors.
Cardiovascular effects of noradrenaline microinjected into the insular cortex of unanesthetized rats
2011, Autonomic Neuroscience: Basic and Clinical
Citation Excerpt :
Moreover, it has also been reported that the IC modulates baroreflex activity in unanesthetized rats (Alves et al., 2009a,b). Cardiovascular responses have been reported after noradrenaline microinjection into medullary structures such as the nucleus of the solitary tract (Zandberg et al., 1979) as well as into supramedullary structures such as the lateral septal area (Scopinho et al., 2006), the amygdala (Ohta et al., 1991), hypothalamic nuclei (Busnardo et al., 2009; Camargo et al., 1979; Harland et al., 1989) and the bed nucleus of the stria terminalis (BST) (Crestani et al., 2008, 2007). These results suggest that central noradrenergic pathways are involved in cardiovascular control.
The insular cortex (IC) has been reported to be involved in central cardiovascular control. In the present study, we investigated the cardiovascular responses evoked by microinjection of noradrenaline into the IC as well as the central and peripheral mechanisms involved in their mediation. Microinjection of noradrenaline into the IC (3, 7, 10, 15, 30 and 45 nmol/100 nL) caused long-lasting dose-related pressor and bradycardiac responses. The cardiovascular responses evoked by 15 nmol of noradrenaline were blocked by IC pretreatment with WB4101 or 5-methyl-urapidil, selective α₁-adrenoceptor antagonists. IC pretreatment with either the selective α₂-adrenoceptor antagonists RX821002 or the β-adrenoceptor antagonist propranolol did not affect noradrenaline cardiovascular responses. Noradrenaline cardiovascular responses were mimicked by microinjection of the selective α₁-adrenoceptor agonist phenylephrine into the IC, thus reinforcing the idea that α₁-adrenoceptors mediate cardiovascular responses to noradrenaline microinjected into the IC. The pressor response to noradrenaline microinjection was potentiated by i.v. pretreatment with the ganglion blocker pentolinium and inhibited by i.v. pretreatment with the selective V₁-vasopressin receptor antagonist dTyr(CH₂)₅(Me)AVP. The bradycardiac response to noradrenaline microinjection into the IC was abolished by pretreatment with either pentolinium or the V₁-vasopressin receptor antagonist, indicating its reflex origin. In conclusion, our results suggest that pressor response evoked by microinjection of noradrenaline into the IC involve the activation of IC α₁-adrenoceptors to cause the release of vasopressin into the circulation.
Dopamine microinjected into brainstem of awake rats affects baseline arterial pressure but not chemoreflex responses
2010, Autonomic Neuroscience: Basic and Clinical
Dopamine (DA) is a neuromodulator in the brainstem involved with the generation and modulation of the autonomic and respiratory activities. Here we evaluated the effect of microinjection of DA intracisterna magna (icm) or into the caudal nucleus tractus solitarii (cNTS) on the baseline cardiovascular and respiratory parameters and on the cardiovascular and respiratory responses to chemoreflex activation in awake rats. Guide cannulas were implanted in cisterna magna or cNTS and femoral artery and vein were catheterized. Respiratory frequency (f_R) was measured by whole-body plethysmography. Chemoreflex was activated with KCN (iv) before and after microinjection of DA icm or into the cNTS bilaterally while mean arterial pressure (MAP), heart rate (HR) and f_R were recorded. Microinjection of DA icm (n = 13), but not into the cNTS (n = 8) produced a significant decrease in baseline MAP (− 15 ± 1 vs 1 ± 1 mm Hg) and HR (− 55 ± 11 vs − 11 ± 17 bpm) in relation to control (saline with ascorbic acid, n = 9) but no significant changes in baseline f_R. Microinjection of DA icm or into the cNTS produced no significant changes in the pressor, bradycardic and tachypneic responses to chemoreflex activation. These data show that a) DA icm affects baseline cardiovascular regulation, but not baseline f_R and autonomic and respiratory components of chemoreflex and b) DA into the cNTS does not affect either the autonomic activity to the cardiovascular system or the autonomic and respiratory responses of chemoreflex activation.
Mechanisms involved in the pressor response to noradrenaline microinjection into the supraoptic nucleus of unanesthetized rats
2009, Autonomic Neuroscience: Basic and Clinical
We report on the cardiovascular effects of noradrenaline (NA) microinjection into the hypothalamic supraoptic nucleus (SON) as well as the central and peripheral mechanisms involved in their mediation. Microinjections of NA 1, 3, 10, 30 or 45 nmol/100 nL into the SON caused dose-related pressor and bradycardiac response in unanesthetized rats. The response to NA 10 nmol was blocked by SON pretreatment with 15 nmol of the alpha(2)-adrenoceptor antagonist RX821002 and not affected by pretreatment with equimolar dose of the selective alpha(1)-adrenoceptor antagonist WB4101, suggesting that local alpha(2)-adrenoceptors mediate these responses. Pretreatment of the SON with the nonselective beta-adrenoceptor antagonist propranolol 15 nmol did not affect the pressor response to NA microinjection of into the SON. Moreover, the microinjection of the 100 nmol of the selective alpha(1)-adrenoceptor agonist methoxamine (MET) into the SON did not cause cardiovascular response while the microinjection of the selective alpha(2)-adrenoceptor agonists BHT920 (BHT, 100 nmol) or clonidine (CLO, 5 nmol) caused pressor and bradycardiac responses, similar to that observed after the microinjection of NA. The pressor response to NA was potentiated by intravenous pretreatment with the ganglion blocker pentolinium and was blocked by intravenous pretreatment with the V(1)-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP, suggesting an involvement of circulating vasopressin in this response. In conclusion, our results suggest that pressor responses caused by microinjections of NA into the SON involve activation of local alpha(2)-adrenoceptor receptors and are mediated by vasopressin release into circulation.
Opposite to α<inf>2</inf>-adrenergic agonists, an imidazoline I<inf>1</inf> selective compound does not influence reflex bradycardia in rabbits
2006, Autonomic Neuroscience: Basic and Clinical
This work aimed to study the respective effects of central α₂-adrenergic receptors (α₂-AR_S) and I₁ imidazoline receptors (I₁Rs) in the facilitatory effects of imidazoline-like drugs on the reflex bradycardia (RB). Experiments were performed in anaesthetized rabbits. The reflex bradycardic response was induced by phenylephrine injected i.v. LNP 509, rilmenidine and dexmedetomidine were administered intracisternally (i.c.).
LNP509 (1 mg/kg, i.c.), a ligand highly selective for I₁Rs, induced hypotension (54 ± 3 vs. 93 ± 2 mm Hg) and bradycardia (260 ± 13 vs. 322 ± 13 beats/min) (p < 0.05, n = 5) but did not affect RB.
Rilmenidine (1 μg/kg, i.c.), a hybrid ligand which binds to both I₁ and α₂-AR_S, also decreased arterial pressure (61 ± 2 vs. 101 ± 2 mm Hg) and heart rate (260 ± 4 vs. 308 ± 8) (p < 0.01, n = 5); it potentiated the RB (maximum R–R interval: 284 ± 17 vs. 196 ± 6 ms) (p < 0.05, n = 5).
Dexmedetomidine (1 μg/kg, i.c.), a ligand selective for α₂-ARs, reduced blood pressure (53 ± 3 vs. 104 ± 2 mm Hg) and heart rate (246 ± 4 vs. 312 ± 8 beats/min) (p < 0.05, n = 5) and potentiated the RB (maximum R–R interval: 518 ± 38 vs. 194 ± 4 ms) (p < 0.05, n = 5). The potentiation of RB was much greater than that observed with rilmenidine and was significantly prevented by L-NNA injected centrally.
This study shows that: (i) an exclusive action on I₁Rs which decreases arterial pressure, does not potentiate the RB ii) activation of α₂-ARs potentiates the RB (iii) the R–R prolongation caused by α₂-ARs stimulation is prevented by central NOS inhibition.
Time course analysis of tyrosine hydroxylase and angiotensinogen mRNA expression in central nervous system of rats submitted to experimental hypertension
2006, Neuroscience Research
Catecholaminergic and angiotensinergic systems are involved in the neural control of blood pressure. The present study analysed the expression of tyrosine hydroxylase (TH), a key enzyme for catecholamine synthesis and of angiotensinogen (AGT), the precursor of angiotensin II (Ang II), in areas of the central nervous system (CNS) involved with cardiovascular regulation such as nucleus tractus solitarius (NTS), ventrolateral medulla (VLM), locus coeruleus (LC) and hypothalamic paraventricular nucleus (PVN) 2 h, 3 and 7 days after aortic coarctated hypertensive rats. In situ hybridization, was employed for the analysis of messenger RNA (mRNA) expression with anatomical resolution.
No changes were seen in TH and AGT mRNA expression in the analysed areas 2 h and 3 days after aortic coarctation when compared to the respective sham group. TH mRNA expression was increased in the NTS and LC of rats 7 days after coarctation hypertension when compared to sham rats. Time course analysis, showed an increase in TH mRNA expression in the NTS 7 days after aortic coarctation when compared to 2 h and 3 days groups, as well as an increase in LC 3 days and 7 days following coarctation hypertension in comparison with the 2 h group.
Analysis of AGT mRNA in the NTS expression revealed a decrease at 3 days, followed by an increase in mRNA expression 7 days following coarctation hypertension when compared to the sham group. Time course analysis, showed an increase in AGT mRNA expression in the NTS 7 days after coarctation when compared to 2 h and 3 days groups.
The results show that TH and AGT mRNA expression changes during the different phases of experimental hypertension, suggesting that the noradrenaline (NOR) and angiotensin II (Ang II) might participate in the modulation/maintenance of coarctation hypertension.

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^∗: Present address: National Institute of Public Health, Pharmacology, Laboratory P.O.Box 1, 3720 BA Bilthoven, The Netherlands.

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Effect of catecholamine-receptor stimulating agents on blood pressure after local application in the nucleus tractus solitarii of the medulla oblongata

Abstract

Life Sci.

Neuropharmacol.

Life Sci.

Brain Res.

European J. Pharmacol.

European J. Pharmacol.

European J. Pharmacol.

European J. Pharmacol.

European J. Pharmacol.

European J. Pharmacol.

European J. Pharmacol.

Brain Res.

European J. Pharmaco.

Brain Res.

Brain Res.