Effect of β1/β2‐adrenoceptor blockade on β3‐adrenoceptor activity in the rat cremaster muscle artery

Saunders, S.; Hutchinson, Dana S.; Britton, Fiona C.; Liu, Lu; Markus, Irit; Sandow, Shaun L.; Murphy, Timothy V.

doi:10.1111/bph.15398

Cited by 4 publications

(3 citation statements)

References 75 publications

(118 reference statements)

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“…It is possible this occurs through the β3-adrenoceptors found on the endothelium, whose function is normally suppressed by β1/2 adrenoceptors. 41 We did not explore whether the β3-adrenoceptor activity was altered following treatment with ciliobrevin D, however, given that propranolol and ICI 118 551 completely inhibited the improved isoprenaline relaxation, it seems unlikely that β3-adrenoceptors play a role. Thus, dynein inhibition increases the isoprenaline-induced relaxation through an increased functional contribution of β2-adrenoceptors.…”

Section: Discussionmentioning

confidence: 99%

“…Isoprenaline binds primarily to β1- and β2-adrenoceptors on arterial smooth muscle cells. 9,40,41 Activation of these receptors leads to increased intracellular cAMP and ultimately vascular smooth muscle relaxation, which occurs in both a hyperpolarization-dependent and -independent manner. 10 Evidence suggests that β1-adrenoceptors predominate, particularly in the rat mesenteric vasculature.…”

Section: Discussionmentioning

confidence: 99%

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Dynein Coordinates β2-Adrenoceptor-Mediated Relaxation in Normotensive and Hypertensive Rat Mesenteric Arteries

et al. 2022

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Background: The voltage-gated potassium channel (Kv)7.4 and Kv7.5 channels contribute to the β-adrenoceptor-mediated vasodilatation. In arteries from hypertensive rodents, the Kv7.4 channel is downregulated and function attenuated, which contributes to the reduced β-adrenoceptor-mediated vasodilatation observed in these arteries. Recently, we showed that disruption of the microtubule network, with colchicine, or inhibition of the microtubule motor protein, dynein, with ciliobrevin D, enhanced the membrane abundance and function of Kv7.4 channels in rat mesenteric arteries. This study aimed to determine whether these pharmacological compounds can improve Kv7.4 function in third-order mesenteric arteries from the spontaneously hypertensive rat, thereby restoring the β-adrenoceptor-mediated vasodilatation. methods: Wire and intravital myography was performed on normotensive and hypertensive male rat mesenteric arteries and immunostaining was performed on isolated smooth muscle cells from the same arteries. Results: Using wire and intravital microscopy, we show that ciliobrevin D enhanced the β-adrenoceptor-mediated vasodilatation by isoprenaline. This effect was inhibited partially by the Kv7 channel blocker linopirdine and was dependent on an increased functional contribution of the β2-adrenoceptor to the isoprenaline-mediated relaxation. In mesenteric arteries from the spontaneously hypertensive rat, ciliobrevin D and colchicine both improved the isoprenaline-mediated vasorelaxation and relaxation to the Kv7.2 -7.5 activator, ML213. Immunostaining confirmed ciliobrevin D enhanced the membrane abundance of Kv7.4. As well as an increase in the function of Kv7.4, the functional changes were associated with an increase in the contribution of β2-adrenoceptor following isoprenaline treatment. Immunostaining experiments showed ciliobrevin D prevented isoprenaline-mediated internalizationof the β2-adrenoceptor. Conclusions: Overall, these data show that colchicine and ciliobrevin D can induce a β2-adrenoceptor-mediated vasodilatation in arteries from the spontaneously hypertensive rat as well as reinstating Kv7.4 channel function.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dynein Coordinates β2-Adrenoceptor-Mediated Relaxation in Normotensive and Hypertensive Rat Mesenteric Arteries

et al. 2022

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“…As we summarized in Aim 1, previous studies consistently show evidence of adrenergic receptor expression within the fetoplacental vasculature (Fig. 3), suggesting that agonist-activated adrenergic receptor pathways may alter vascular tone in the fetoplacental circulation [40,44,48,49,52,55–83].…”

Section: Methodsmentioning

confidence: 52%

Fetoplacental vascular effects of maternal adrenergic antihypertensive and cardioprotective medications in pregnancy

Tropea,

Mavichak,

Evangelinos

et al. 2023

Journal of Hypertension

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Maternal cardiovascular diseases, including hypertension and cardiac conditions, are associated with poor fetal outcomes. A range of adrenergic antihypertensive and cardioprotective medications are often prescribed to pregnant women to reduce major maternal complications during pregnancy. Although these treatments are not considered teratogenic, they may have detrimental effects on fetal growth and development, as they cross the fetoplacental barrier, and may contribute to placental vascular dysregulation. Medication risk assessment sheets do not include specific advice to clinicians and women regarding the safety of these therapies for use in pregnancy and the potential off-target effects of adrenergic medications on fetal growth have not been rigorously conducted. Little is known of their effects on the fetoplacental vasculature. There is also a dearth of knowledge on adrenergic receptor activation and signalling within the endothelium and vascular smooth muscle cells of the human placenta, a vital organ in the maintenance of adequate blood flow to satisfy fetal growth and development. The fetoplacental circulation, absent of sympathetic innervation, and unique in its reliance on endocrine, paracrine and autocrine influence in the regulation of vascular tone, appears vulnerable to dysregulation by adrenergic antihypertensive and cardioprotective medications compared with the adult peripheral circulation. This semi-systematic review focuses on fetoplacental vascular expression of adrenergic receptors, associated cell signalling mechanisms and predictive consequences of receptor activation/deactivation by antihypertensive and cardioprotective medications.

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The β3 adrenoceptor in proliferative retinopathies: “Cinderella” steps out of its family shadow

Cammalleri

Amato

Monte

et al. 2023

Pharmacological Research

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Effect of β₁/β₂‐adrenoceptor blockade on β₃‐adrenoceptor activity in the rat cremaster muscle artery

Cited by 4 publications

References 75 publications

Dynein Coordinates β2-Adrenoceptor-Mediated Relaxation in Normotensive and Hypertensive Rat Mesenteric Arteries

Dynein Coordinates β2-Adrenoceptor-Mediated Relaxation in Normotensive and Hypertensive Rat Mesenteric Arteries

Fetoplacental vascular effects of maternal adrenergic antihypertensive and cardioprotective medications in pregnancy

The β3 adrenoceptor in proliferative retinopathies: “Cinderella” steps out of its family shadow

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