Characterization of beta-adrenoceptor subtypes in rat kidney with new highly selective β1 blockers and their role in renin release

M, Milavec-Krizman; Jp, Evenou; Wagner, H.; Berthold, R.; Ap, Stoll

doi:10.1016/0006-2952(85)90371-5

Cited by 29 publications

(5 citation statements)

References 10 publications

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“…However, losartan did not eliminate the hampering effect of atenolol or metoprolol on norepinephrine overflow in WKY or SHR, and atenolol reduced tyramine-induced norepinephrine overflow also in 24-h NX rats. It was therefore concluded that the stimulating effect of β 1 AR on norepinephrine release was not mediated through activation of renal renin secretion (21), with subsequent activation of presynaptic, release-stimulating AT1R (Figure 1). Atenolol reduced norepinephrine release also in AdrX + losartan-pre-treated WKY.…”

Section: Discussionmentioning

confidence: 99%

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

Berg

2014

Front. Neurol.

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Peripheral norepinephrine release is facilitated by presynaptic β-adrenoceptors, believed to involve the β2-subtype exclusively. However, β1-selective blockers are the most commonly used β-blockers in hypertension. Here the author tested the hypothesis that β1AR may function as presynaptic, release-facilitating auto-receptors. Since β1AR-blockers are injected during myocardial infarction, their influence on the cardiovascular response to acute norepinephrine release was also studied. By a newly established method, using tyramine-stimulated release through the norepinephrine transporter (NET), presynaptic control of catecholamine release was studied in normotensive and spontaneously hypertensive rats. β1AR-selective antagonists (CGP20712A, atenolol, metoprolol) reduced norepinephrine overflow to plasma equally efficient as β2AR-selective (ICI-118551) and β1+2AR (nadolol) antagonists in both strains. Neither antagonist lowered epinephrine secretion. Atenolol, which does not cross the blood–brain barrier, reduced norepinephrine overflow after adrenalectomy (AdrX), AdrX + ganglion blockade, losartan, or nephrectomy. Atenolol and metoprolol reduced resting cardiac work load. During tyramine-stimulated norepinephrine release, they had little effect on work load, and increased the transient rise in total peripheral vascular resistance, particularly atenolol when combined with losartan. In conclusion, β1AR, like β2AR, stimulated norepinephrine but not epinephrine release, independent of adrenal catecholamines, ganglion transmission, or renal renin release/angiotensin AT1 receptor activation. β1AR therefore functioned as a peripheral, presynaptic, facilitating auto-receptor. Like tyramine, hypoxia may induce NET-mediated release. Augmented tyramine-induced vasoconstriction, as observed after injection of β1AR-blocker, particularly atenolol combined with losartan, may hamper organ perfusion, and may have clinical relevance in hypoxic conditions such as myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

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

Berg

2014

Front. Neurol.

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“…Miyamoto et al showed that ß1-ARs are downregulated in both adults and children with chronic HF but that the ß2-AR is downregulated only in pediatric DCM. She stated “Further inhibition of the already downregulated ß2-ARs may override the benefit of ß1-AR inhibitor therapy, because preservation of ß2-AR function is beneficial.” In addition, several studies support the cardio-protective effect of short-term beta-2 stimulation [ 4 , 5 , 9 , 17 , 31 , 32 , 38 , 45 , 63 ]. Bisoprolol is a long-acting, highly cardio-selective BAR-blocker, with a low side effect profile.…”

Section: Recommendations To Improve Chronic Hf Treatment In Infants Amentioning

confidence: 99%

“Nihilism” of chronic heart failure therapy in children and why effective therapy is withheld

Schranz

Voelkel

2016

Eur J Pediatr

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Major advances in chronic heart failure (cHF) therapy have been achieved and documented in adult patients, while research regarding the mechanisms and therapy of cHF in children has lagged behind. Based on receptor physiological studies and pharmacological knowledge, treatment with specific ß1-adrenergic receptor blocker (ARB), tissue angiotensin-converting enzyme inhibitor (ACE-I), and mineralocorticoid antagonists have to be recommended in children despite lack of sufficient data derived from prospective randomized studies. At our institution, bisoprolol, lisinopril, and spironolactone have been firmly established to treat systolic cHF, hypoplastic left heart syndrome (HLHS) following hybrid approach and congenital left-right shunt diseases, latest in patients where surgery has to be delayed. Chronic therapy with long-acting diuretics and fluid restriction are not advocated because short-term effects are achieved at the expense of further neuro-humoral stimulation. It remains unclear why diuretics are recommended although evidence-based studies, documenting long-term benefit, are missing. However, that is true for all currently used drugs for pediatric cHF.Conclusion: This review focuses on the prevailing “nihilism” of cHF therapy in children with the goal to encourage physicians to treat pediatric cHF with a rationally designed therapy, which combines available agents that have been shown to improve survival in adult patients with cHF. Because of the lack of clinical trials, which generate the needed evidence, surrogate variables like heart and respiratory rate, weight gain, image-derived data, and biomarkers should be monitored and used instead. The recommended pharmacological therapy for systolic heart failure is also provided as the basis for utilizing reversible pulmonary arterial banding (PAB) as a novel strategy in young children with dilative cardiomyopathy (DCM) with preserved right ventricular function. What is Known: • Heart failure (HF) in children is a serious public health concern. • HF has numerous etiologies, but unspecific symptoms. • HF interplays among neuro-humoral, and molecular abnormalities. • Pediatric cHF-therapy is currently based on loop-diuretics, fluid restriction and digoxin. What is New: • Cardiac function analysis has to include cardiac synchrony and VVI. • Considering enormous potential of cardiac regeneration, therapy has to extend with selective ß1-ARB, tissue ACE-I and mineralocorticoid blockers, loop-diuretics avoided as ever possible. • Inhibition of the endogenous neuro-humoral stimulation is monitored by surrogate parameters as heart and breath rate and systolic and diastolic blood pressure. • Advocated HF therapy serves for regenerative strategies as reversible Pulmonary Artery Banding in DCM. Electronic supplementary materialThe online version of this article (doi:10.1007/s00431-016-2700-3) contains supplementary material, which is available to authorized users.

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“…β 2 AR has been shown to regulate the expression of Na/Cl co-transporter expression, thereby participating in the development of salt sensitive hypertension [168,169]. Furthermore, βAR located on the iuxtaglomerular cells mediates renin release [170]. The actual number of β 2 ARs is significantly reduced in membrane preparations of aged rat kidney compared with the young animals [171].…”

Section: Introductionmentioning

confidence: 99%

Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes

Santulli

Iaccarino

2013

Immun Ageing

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G protein-coupled receptors (GPCRs) play a key role in cellular communication, allowing human cells to sense external cues or to talk each other through hormones or neurotransmitters. Research in this field has been recently awarded with the Nobel Prize in chemistry to Robert J. Lefkowitz and Brian K. Kobilka, for their pioneering work on beta adrenergic receptors (βARs), a prototype GPCR. Such receptors, and β2AR in particular, which is extensively distributed throughout the body, are involved in a number of pathophysiological processes. Moreover, a large amount of studies has demonstrated their participation in ageing process. Reciprocally, age-related changes in regulation of receptor responses have been observed in numerous tissues and include modifications of βAR responses. Impaired sympathetic nervous system function has been indeed evoked as at least a partial explanation for several modifications that occur with ageing. This article represents an updated presentation of the current knowledge in the field, summarizing in a systematic way the major findings of research on ageing in several organs and tissues (crime scenes) expressing βARs: heart, vessels, skeletal muscle, respiratory system, brain, immune system, pancreatic islets, liver, kidney and bone.

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Characterization of beta-adrenoceptor subtypes in rat kidney with new highly selective β1 blockers and their role in renin release

Cited by 29 publications

References 10 publications

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

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

“Nihilism” of chronic heart failure therapy in children and why effective therapy is withheld

Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes

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