Î²1-Blockers Lower Norepinephrine Release by Inhibiting Presynaptic, Facilitating Î²1-Adrenoceptors in Normotensive and Hypertensive Rats

Berg, Torill

doi:10.3389/fneur.2014.00051

Cited by 33 publications

(42 citation statements)

References 33 publications

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“…Despite metoprolol being a selective postsynaptic β 1 ‐adrenoceptor inhibitor acting mainly on cardiac receptors, it has been shown that it also lowers plasma norepinephrine levels and release, by inhibiting presynaptic facilitating adrenoceptors in rats 50. This fits very well with our observation of reduced catecholamine levels after chronic metoprolol treatment in stroke animals.…”

Section: Discussionsupporting

confidence: 88%

Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity

Bieber

Werner

Tanai

et al. 2017

Annals of Neurology

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ObjectiveCardiac diseases are established risk factors for ischemic stroke incidence and severity. Conversely, there is increasing evidence that brain ischemia can cause cardiac dysfunction. The mechanisms underlying this neurogenic heart disease are incompletely understood. Although it is established that ischemic stroke is associated with cardiac arrhythmias, myocardial damage, elevated cardiac enzymes, and plasma catecholamines in the acute phase, nothing is known about the delayed consequences of ischemic stroke on cardiovascular function.MethodsTo determine the long‐term cardiac consequences of a focal cerebral ischemia, we subjected young and aged mice to a 30‐minute transient middle cerebral artery occlusion and analyzed cardiac function by serial transthoracic echocardiography and hemodynamic measurements up to week 8 after surgery. Finally, animals were treated with metoprolol to evaluate a pharmacologic treatment option to prevent the development of heart failure.ResultsFocal cerebral ischemia induced a long‐term cardiac dysfunction with a reduction in left ventricular ejection fraction and an increase in left ventricular volumes; this development was associated with higher peripheral sympathetic activity. Metoprolol treatment prevented the development of chronic cardiac dysfunction by decelerating extracellular cardiac remodeling and inhibiting sympathetic signaling relevant to chronic autonomic dysfunction.InterpretationFocal cerebral ischemia in mice leads to the development of chronic systolic dysfunction driven by increased sympathetic activity. If these results can be confirmed in a clinical setting, treating physicians should be attentive to clinical signs of heart failure in every patient after ischemic stroke. Therapeutically, the successful β‐blockade with metoprolol in mice could also have future clinical implications. Ann Neurol 2017;82:729–743

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Section: Discussionsupporting

confidence: 88%

Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity

Bieber

Werner

Tanai

et al. 2017

Annals of Neurology

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“…The α 2 AR-mediated auto-inhibition of release of NE and also epinephrine was functional in male WKY but not in the male SHR (4, 5). However, α 2 AR clearly inhibited release of both catecholamines in the female SHR (3).…”

Section: Introductionmentioning

confidence: 84%

“…However, the trauma induced by the surgical procedure activated some secretion of epinephrine, also subjected to receptor-mediated release control (3, 4, 13). Removal of the adrenal glands did not alter the plasma NE concentration, indicating that tyramine stimulated the release of NE from sympathetic nerves rather than from NE-producing cells in the adrenal medulla (5). The tyramine-induced NE release activated a cardiovascular response.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, in male rats, losartan greatly increased the TPR and MBP responses to NE release when combined with atenolol, particularly in WKY (5). It is not known if this occurs also in female rats.…”

Section: Introductionmentioning

confidence: 96%

“…However, α 2 AR clearly inhibited release of both catecholamines in the female SHR (3). In male rats, both β 1 - and β 2 AR-facilitated release (5), and strain-related differences in the interaction between α 2 AR and β 1/2 AR were observed (6). The role of β 1+2 AR in the control of catecholamine release and their interaction with the α 2 AR has not been studied in the female SHR.…”

Section: Introductionmentioning

confidence: 99%

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β- and α2-Adrenoceptor Control of Vascular Tension and Catecholamine Release in Female Normotensive and Spontaneously Hypertensive Rats

Berg

2017

Front. Neurol.

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As in humans, young, female, spontaneously hypertensive rats (SHR) have a lower blood pressure than male SHR. In male, normotensive rats (WKY), α2- and β1+2-adrenoceptors (AR) reciprocally controlled catecholamine release and vascular smooth muscle tension. This interaction was malfunctioning in male SHR. The present study analyzed if a favorable shift in the α2/β1+2AR interaction may represent an antihypertensive protection in females. Female SHR (early hypertension, 12–14 weeks) and age-matched WKY were infused with tyramine (15 min) to stimulate norepinephrine (NE) release through the reuptake transporter, consequently preventing reuptake. Presynaptic control of vesicular release was therefore reflected as differences in overflow to plasma. The released NE increased total peripheral vascular resistance (TPR). The results showed that β1>2AR facilitated tyramine-stimulated NE release in both strains, also in the presence of α2AR-antagonist (L-659,066). βAR-antagonist (atenolol-β1, ICI-118551-β2, nadolol-β1+2) had no effect on the increased secretion of epinephrine after L-659,066 in WKY, but β1>2AR-antagonist augmented the L-659,066-induced increase in the secretion of epinephrine in SHR. Nadolol increased the TPR response to tyramine with a greater effect in WKY than SHR, whereas β1or2-selective antagonists did not. One βAR-subtype may therefore substitute for the other. When both β1+2AR were blocked, α2AR-antagonist still reduced the TPR response in WKY but not SHR. Thus, α2/β1+2AR reciprocally controlled catecholamine release, with a particular negative β1AR-influence on α2AR-auto-inhibition of epinephrine secretion in SHR. Moreover, in these female rats, β1/2AR-independent α2AR-mediated vasoconstriction was seen in WKY but not SHR, but β1/2AR-mediated vasodilation downregulated adrenergic vasoconstriction, not only in WKY but also in SHR.

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Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System

Wehrwein

Orer

Barman

2016

Comprehensive Physiology

318

232

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Comprised of the sympathetic nervous system, parasympathetic nervous system, and enteric nervous system, the autonomic nervous system (ANS) provides the neural control of all parts of the body except for skeletal muscles. The ANS has the major responsibility to ensure that the physiological integrity of cells, tissues, and organs throughout the entire body is maintained (homeostasis) in the face of perturbations exerted by both the external and internal environments. Many commonly prescribed drugs, over-the-counter drugs, toxins, and toxicants function by altering transmission within the ANS. Autonomic dysfunction is a signature of many neurological diseases or disorders. Despite the physiological relevance of the ANS, most neuroscience textbooks offer very limited coverage of this portion of the nervous system. This review article provides both historical and current information about the anatomy, physiology, and pharmacology of the sympathetic and parasympathetic divisions of the ANS. The ultimate aim is for this article to be a valuable resource for those interested in learning the basics of these two components of the ANS and to appreciate its importance in both health and disease. Other resources should be consulted for a thorough understanding of the third division of the ANS, the enteric nervous system. © 2016 American Physiological Society. Compr Physiol 6:1239-1278, 2016.

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Î²1-Blockers Lower Norepinephrine Release by Inhibiting Presynaptic, Facilitating Î²1-Adrenoceptors in Normotensive and Hypertensive Rats

Cited by 33 publications

References 33 publications

Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity

Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity

β- and α2-Adrenoceptor Control of Vascular Tension and Catecholamine Release in Female Normotensive and Spontaneously Hypertensive Rats

Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System

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