Facilitation of noradrenaline release from sympathetic nerves in rat anococcygeus muscle by activation of prejunctional β‐adrenoceptors and angiotensin receptors

Li, Chun Guang; Majewski, H.; Rand, M. J.

doi:10.1111/j.1476-5381.1988.tb11657.x

Cited by 21 publications

(14 citation statements)

References 21 publications

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confidence: 95%

“…It is out of keeping with the typically absent or rather trifling stimulatory or antiadrenergic neural effects typically seen in humans when angiotensin is infused or the renin-angiotensin system is blocked by angiotensin-converting enzyme (ACE) inhibitors, respectively. There is, in fact, a striking mismatch between these absent or minimal sympathetic neural effects of angiotensin administration and angiotensin blockade in humans (1,16,17,25,43) and the prominent sympathetic neural stimulation produced by angiotensin in laboratory experiments (2,6,10,27,42).One concept of particular clinical interest is the claim that angiotensin receptor blocking agents (ARBs) may, by blocking the presynaptic ANG II type 1 (AT 1 ) receptor, reduce ANG II-mediated facilitation of neurally sustained vascular tone, contributing to the antihypertensive action (3,33). Although in most studies in humans angiotensin administration has not been observed to increase central sympathetic outflow (16), a small but measurable presynaptic stimulatory neural action of angiotensin has been unequivocally demonstrated in the sympathetic nerves of the forearm (5).…”

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confidence: 96%

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Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension

Krum¹,

Lambert²,

Windebank³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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It has long been proposed that the renin-angiotensin system exerts a stimulatory influence on the sympathetic nervous system, including augmentation of central sympathetic outflow and presynaptic facilitation of norepinephrine release from sympathetic nerves. We tested this proposition in 19 patients with essential hypertension, evaluating whether the angiotensin receptor blockers (ARBs) eprosartan and losartan had identifiable antiadrenergic properties. This was done in a prospective, randomized, three-way placebo-controlled study of crossover design. Patients were randomized to 600 mg of eprosartan daily, 50 mg of losartan daily, or placebo. The treatment period was 4 wk, with 2-wk washout periods. Multiunit firing rates in efferent sympathetic nerves distributed to skeletal muscle vasculature (muscle sympathetic nerve activity, MSNA) were measured with microneurography, testing whether ARBs inhibit central sympathetic outflow. In parallel, isotope dilution methodology was used to measure whole body norepinephrine spillover to plasma. Mean blood pressure on placebo was 151/98 mmHg, with both ARBs causing reductions of approximately 11 mmHg systolic and 6 mmHg diastolic pressure, placebo corrected. Both MSNA [35 +/- 12 bursts/min (mean +/- SD) on placebo] and whole body norepinephrine spillover [366 +/- 247 ng/min] were unchanged by ARB administration, indicating that the ARBs did not materially inhibit central sympathetic outflow or act presynaptically to reduce norepinephrine release at existing rates of nerve firing. These findings contrast with the easily demonstrable reduction in sympathetic nervous activity produced by antihypertensive drugs of the imidazoline-binding class, which are known to act within the brain to inhibit sympathetic nervous outflow. We conclude that sympathetic nervous inhibition is not a major component of the blood pressure-lowering action of ARBs in essential hypertension.

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confidence: 95%

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confidence: 96%

Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension

Krum¹,

Lambert²,

Windebank³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Since Ang II activates prejunctional receptors located at sympathetic neurons of the rat anococcygeus (Li et al, 1988), we evaluated the nature of these receptors by incubating the tissue in the presence of prazosin, losartan, and PD123319. Prazosin inhibited the Ang II-induced contractions, confirming that Ang II is, in part, an indirect-acting agonist, which could contribute to the apparent noncompetitive antagonism of losartan.…”

Section: De Godoy and De Oliveiramentioning

confidence: 99%

“…Activation of the prejunctional receptor results in enhancement of norepinephrine (NE) release, which induces contractile response by activation of postjunctional ␣ 1 -adrenoceptors (Doggrell and Woodruff, 1978;James and Leighton, 1987;Li et al, 1988). The ultrastructure of nerve terminals in the rat anococcygeus muscle also offers support for a nonadrenergic, noncholinergic enervation of approximately 40% of the nerve terminals (Gibbins and Haller, 1979).…”

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confidence: 99%

Cross-Talk Between AT₁ and AT₂Angiotensin Receptors in Rat Anococcygeus Smooth Muscle

Godoy

Oliveira²

2002

J Pharmacol Exp Ther

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Schild regressions for the selective AT 1 and AT 2 receptor antagonists, losartan and PD123319 (S-[ϩ]-1-[(4-dimethylamino]-3-methylphenyl)methyl]-5- [diphenylacetyl]-4,5,6,7-tetrahydro-1H-imidazol[4,5-c]pyridine-6-carboxilic acid), respectively, were calculated to analyze the heterogeneity of receptor populations in the rat anococcygeus muscle. For a one-receptor system, the Schild regression has a slope of unity and an intercept of K B for competitive antagonists. However, in a two-receptor system, a deviation from the single-receptor plot will occur. This is predicated on the assumption that the secondary receptor is less sensitive to the antagonist than the primary receptor. Results showed that the Schild regression for losartan did not produce a slope of unity, and PD123319 did not produce any effect. However, tissue incubation with losartan plus PD123319 resulted in a Schild regression that has a slope of unity and a pK B of 9.32. In the presence of prazosin, an ␣ 1 -adrenoceptor antagonist, losartan did not produce any effect. Conversely, PD123319 enhanced the angiotensin II (Ang II)-induced contraction in a concentration-dependent fashion, suggesting an inhibitory AT 2 -mediated effect. This effect was confirmed with assays that showed a relaxant response induced by Ang II on precontracted tissues incubated with prazosin. PD123319 and N G -nitro-L-arginine methyl ester [nitric-oxide (NO) synthase inhibitor)] markedly inhibited the relaxant response of Ang II. In contrast, losartan did not produce any significant effect. Consequently, results show that the mechanism underlying the AT 2 -mediated effect is highly dependent on NO generation. Results indicate the presence of a heterogeneous angiotensin receptor population in the rat anococcygeus muscle following a negative cross-talk relationship between the AT 1 and AT 2 subtypes.

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“…Rat and mouse anococcygeus muscles Anococcygeus muscles were set up, as described by Li et al (1988) for rat and by Gibson & Wedmore (1981) for mouse, in 5 ml organ baths for isometric recording and field stimulation (tension: rat, 1 g wt; mouse, 0.3 g wt).…”

Section: Preparation Of Isolated Tissuesmentioning

confidence: 99%

Effects of ω‐conotoxin GVIA on autonomic neuroeffector transmission in various tissues

Luca

Rand

et al. 1990

British J Pharmacology

101

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1 The effects of co-conotoxin GVIA (conotoxin), a potent inhibitor of neuronal N-type Ca2+ channels, have been examined on responses to stimulation of noradrenergic, cholinergic and non-adrenergic, noncholinergic (NANC) nerves in a range of isolated tissues to investigate the role of conotoxin-sensitive Ca2 + channels in neurotransmission. 2 Contractions elicited by field stimulation of noradrenergic nerves in rat and mouse anococcygeus muscles, rabbit ear artery and rat vas deferens (epididymal portion) were inhibited by conotoxin. Responses to noradrenaline, and to adenosine triphosphate in the vas deferens, were not affected. 3 Positive chronotropic responses to field stimulation of noradrenergic nerves were inhibited by conotoxin in rat and mouse atria, but responses to noradrenaline and tyramine were not affected. 4 The stimulation-induced release of noradrenaline was inhibited by conotoxin in the rabbit ear artery and in rat and mouse atria. 5 Relaxations in response to stimulation of the noradrenergic perivascular mesenteric nerves were reduced or abolished by conotoxin in rat and rabbit jejunum. The response to noradrenaline in rat jejunum was not affected. 6 Contractions elicited by stimulation of cholinergic nerves were inhibited by conotoxin in rat jejunum and mouse ileum (perivascular mesenteric nerves), and in guinea-pig taenia caeci (field stimulation). Responses to acetylcholine in rat jejunum and mouse ileum were not affected. 7 Contractions elicted by stimulation of the cholinergic plus NANC pelvic nerves were inhibited by conotoxin in rabbit colon, and to a lesser extent in guinea-pig colon. The stimulation-induced contraction of the guinea-pig colon was inhibited by conotoxin by a greater proportion in the presence than in the absence of atropine. Responses to acetylcholine were not affected in the rabbit colon but were slightly reduced in the guinea-pig colon. 8 Relaxations in response to field stimulation of NANC nerves were inhibited by conotoxin in guineapig taenia caeci and rat gastric fundus strips, and in rat anococcygeus muscle when the tone was raised by guanethidine but not when it was raised by carbachol. The relaxations produced by sodium nitroprusside in the rat gastric fundus and anococcygeus were not affected. 9 Contractions of the rat bladder elicited by stimulation of the peri-urethral nerves, which are NANCand cholinergically mediated, were relatively insensitive to inhibition by conotoxin. The responses were almost completely abolished by tetrodotoxin. 10 The conotoxin-induced inhibitions of responses to nerve stimulation developed slowly and persisted after removal of conotoxin.11 The inhibitory effect of conotoxin was inversely proportional to the frequency of stimulation (in several preparations) and to the Ca2+ concentration in the bathing solution (in rat vas deferens). These observations suggest that the inhibition by conotoxin of the Ca2+ influx required for excitation-secretion coupling in autonomic nerve terminals is not absolute, and can be overcome by repeated st...

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Facilitation of noradrenaline release from sympathetic nerves in rat anococcygeus muscle by activation of prejunctional β‐adrenoceptors and angiotensin receptors

Cited by 21 publications

References 21 publications

Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension

Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension

Cross-Talk Between AT₁ and AT₂Angiotensin Receptors in Rat Anococcygeus Smooth Muscle

Effects of ω‐conotoxin GVIA on autonomic neuroeffector transmission in various tissues

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Facilitation of noradrenaline release from sympathetic nerves in rat anococcygeus muscle by activation of prejunctional β‐adrenoceptors and angiotensin receptors

Cited by 21 publications

References 21 publications

Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension

Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension

Cross-Talk Between AT1 and AT2Angiotensin Receptors in Rat Anococcygeus Smooth Muscle

Effects of ω‐conotoxin GVIA on autonomic neuroeffector transmission in various tissues

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Product

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Cross-Talk Between AT₁ and AT₂Angiotensin Receptors in Rat Anococcygeus Smooth Muscle