Angiotensin II type 2 receptor-mediated vasodilation. Focus on bradykinin, NO and endothelium-derived hyperpolarizing factor(s)

Batenburg, Wendy W.; Tom, Beril; Schuijt, Martin P; Danser, A.H. Jan

doi:10.1016/j.vph.2005.01.005

Cited by 41 publications

(38 citation statements)

References 76 publications

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“…Receptor glycosylation can influence receptor occupancy and ligand binding affinity (53). Another possibility is that changes in expression of the angiotensin (AT) type 2 (AT 2 ) receptor can accentuate the potency of bradykinin (7,92). Indeed, in the mouse lung, AT 2 receptor mRNA expression increases following antenatal hypoxia, while AT 1 receptor expression remains stable (34).…”

Section: Discussionmentioning

confidence: 99%

Developmental acceleration of bradykinin-dependent relaxation by prenatal chronic hypoxia impedes normal development after birth

Blum-Johnston

Thorpe

Wee

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Bradykinin-induced activation of the pulmonary endothelium triggers nitric oxide production and other signals that cause vasorelaxation, including stimulation of largeconductance Ca 2ϩ -activated K ϩ (BKCa) channels in myocytes that hyperpolarize the plasma membrane and decrease intracellular Ca 2ϩ . Intrauterine chronic hypoxia (CH) may reduce vasorelaxation in the fetal-to-newborn transition and contribute to pulmonary hypertension of the newborn. Thus we examined the effects of maturation and CH on the role of BKCa channels during bradykinin-induced vasorelaxation by examining endothelial Ca 2ϩ signals, wire myography, and Western immunoblots on pulmonary arteries isolated from near-term fetal (ϳ140 days gestation) and newborn, 10-to 20-day-old, sheep that lived in normoxia at 700 m or in CH at high altitude (3,801 m) for Ͼ100 days. CH enhanced bradykinin-induced relaxation of fetal vessels but decreased relaxation in newborns. Endothelial Ca 2ϩ responses decreased with maturation but increased with CH. Bradykinin-dependent relaxation was sensitive to 100 M nitro-L-arginine methyl ester or 10 M 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, supporting roles for endothelial nitric oxide synthase and soluble guanylate cyclase activation. Indomethacin blocked relaxation in CH vessels, suggesting upregulation of PLA2 pathways. BKCa channel inhibition with 1 mM tetraethylammonium reduced bradykinin-induced vasorelaxation in the normoxic newborn and fetal CH vessels. Maturation reduced whole cell BKCa channel ␣1-subunit expression but increased ␤1-subunit expression. These results suggest that CH amplifies the contribution of BKCa channels to bradykinin-induced vasorelaxation in fetal sheep but stunts further development of this vasodilatory pathway in newborns. This involves complex changes in multiple components of the bradykinin-signaling axes. potassium channels; sheep; pulmonary artery; contractility; maturation; hypoxia REGULATION OF SMOOTH MUSCLE tone in pulmonary arteries during development is a delicate balance of vasoconstrictive and vasorelaxant pathways. Endothelial cells play a crucial role in determining the overall level of vasorelaxation (39, 67), and endothelium-dependent relaxation is partially mediated through bradykinin stimulation (31). Bradykinin is a potent vasodilator that is important in the fetal pulmonary circulation, as well as during inflammation, and its relationship to pulmonary hypertension has been explored (5, 31, 83).Endothelial bradykinin receptor activation induces vasorelaxation through modulation of several different intracellular signaling pathways that are largely dependent on a rise of endothelial intracellular Ca 2ϩ ([Ca 2ϩ ] i ) (67). The most widely studied pathway is bradykinin-induced activation of endothelial nitric oxide (NO) synthase (eNOS), an enzyme that generates NO (64). NO acts on nearby smooth muscle cells to cause downstream stimulation of soluble guanylate cyclase (sGC) pathways that leads to vasorelaxation (3,45). Previous studies have shown that regulatio...

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Section: Discussionmentioning

confidence: 99%

Developmental acceleration of bradykinin-dependent relaxation by prenatal chronic hypoxia impedes normal development after birth

Blum-Johnston

Thorpe

Wee

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Both ATR subtypes are expressed in UVSM throughout reproduction and pregnancy; thus, we determined whether there was a functional interaction between subtypes during ANG II exposure as reported in small mammals (5,10,56). We first examined the effects of subtype inhibition on ANG IImediated contractions in third generation (Fig.…”

Section: R63 Uteroplacental Sensitivity To Ne and Ang IImentioning

confidence: 99%

“…UTEROPLACENTAL SENSITIVITY TO NE AND ANG II AT 2 R predominance is an attractive explanation for the attenuated UVSM responses to ANG II; however, AT 2 R activation might contribute by increasing endothelial NO synthesis and VSM relaxation (5,10). For example, AT 1 R blockade in rodents induces vasodilation after ANG II exposure, and AT 2 R blockade enhances pressor responses (56).…”

Section: R65mentioning

confidence: 99%

Defining the differential sensitivity to norepinephrine and angiotensin II in the ovine uterine vasculature

Rosenfeld

DeSpain

Liu

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Rosenfeld CR, DeSpain K, Liu X-t. Defining the differential sensitivity to norepinephrine and angiotensin II in the ovine uterine vasculature. Am J Physiol Regul Integr Comp Physiol 302: R59-R67, 2012. First published October 26, 2011 doi:10.1152/ajpregu.00424.2011The intact ovine uterine vascular bed (UVB) is sensitive to ␣-agonists and refractory to angiotensin II (ANG II) during pregnancy; the converse occurs in the systemic circulation. The mechanism(s) responsible for these differences in uterine sensitivity are unclear and may reflect predominance of nonconstricting AT2 receptors (AT2R) in uterine vascular smooth muscle (UVSM). The contribution of the placental vasculature also is unclear. Third generation and precaruncular/placental arteries from nonpregnant (n ϭ 16) and term pregnant (n ϭ 23) sheep were used to study contraction responses to KCl, norepinephrine (NE), and ANG II (with/without ATR specific inhibitors) and determine UVSM ATR subtype expression and contractile protein content. KCl and NE increased third generation and precaruncular/ placental UVSM contractions in a dose-and pregnancy-dependent manner (P Յ 0.001). ANG II only elicited modest contractions in third generation pregnant UVSM (P ϭ 0.04) and none in precaruncular/placental UVSM. Moreover, compared with KCl and NE, ANG II contractions were diminished Ն 5-fold. Whereas KCl and ANG II contracted third generationϾϾprecaruncular/placental UVSM, NEinduced contractions were similar throughout the UVB. However, each agonist increased third generation contractions Ն 2-fold at term, paralleling increased actin/myosin and cellular protein content (P Յ 0.01). UVSM AT 1R and AT2R expression was similar throughout the UVB and unchanged during pregnancy (P Ͼ 0.1). AT 1R inhibition blocked ANG II-mediated contractions; AT 2R blockade, however, did not enhance contractions. AT 2R predominate throughout the UVB of nonpregnant and pregnant sheep, contributing to an inherent refractoriness to ANG II. In contrast, NE elicits enhanced contractility throughout the ovine UVB that exceeds ANG II and increases further at term pregnancy. placental artery; systemic artery; actin/myosin; angiotensin II receptors; ␣-agonists OVINE PREGNANCY IS ASSOCIATED with numerous cardiovascular changes (43, 48), including a Ͼ30-fold rise in uterine blood flow (UBF) and Ͼ40% increase in cardiac output. Additionally, there is development of refractoriness to the pressor effects of infused norepinephrine (NE) and angiotensin II (ANG II) in women and sheep (44,49,53). Although the ovine uterine vascular bed (UVB) also develops refractoriness to these agonists during pregnancy (32, 49), Naden and Rosenfeld (36) reported that the intact pregnant ovine UVB was more refractory to the vasoconstricting effects of ANG II than the systemic vasculature. Thus, blood pressure increased in the absence of significant decreases in uteroplacental blood flow (UPBF). In contrast, the UVB was quite sensitive to ␣-agonists, which decreased ovine UPBF at nonpressor doses, demonstrating differenc...

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“…38 In pregnant C57BL/6J mice, the contractile response of isolated umbilical arteries to ANG II is increased in the presence of the AT2R inhibitor, PD 123319, 46 thus supporting a vasodilatory role for AT2Rs. In contrast, recent studies in isolated umbilical arteries removed from pregnant and non-pregnant women showed that ANG II induced vascular contractions were not altered in the presence of AT2R inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…From these observations, we postulated that, in the newborn period when the RAS is normally activated, AT2Rs may buffer the haemodynamic effects of AT1Rs, as they do later in life. 37,38 The present experiments were, therefore, carried out to investigate the potential role of AT2Rs in modulating the responses to AT1R activation in conscious lambs, by exploring the haemodynamic effects of combined inhibition of both ATRs. To this end, haemodynamic effects of an AT1R antagonist alone, an AT2R antagonist alone, and antagonists to both AT1R and AT2R combined were measured in conscious lambs aged ~1 week -when circulating levels of ANG II are increased and AT2Rs predominate in the conduit arteries -and ~6 weeks -when circulating ANG II levels as well as AT2R expression are decreased.…”

Section: Introductionmentioning

confidence: 99%

Do Angiotensin Type 2 Receptors Modulate Haemodynamic Effects of Type 1 Receptors in Conscious Newborn Lambs?

Vinturache

Smith

2014

J Renin Angiotensin Aldosterone Syst

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Introduction and hypothesis: It was hypothesized that in the immediate newborn period, when the renin-angiotensin system (RAS) is activated, angiotensin type 2 receptors (AT2Rs) buffer the haemodynamic effects of angiotensin type 1 receptors (AT1Rs), as occurs in adult animals when the RAS is activated. Materials and methods: Arterial (systolic, diastolic, and mean) pressures (SAP, DAP, MAP), mean venous pressures (MVP) and renal blood flows (RBF) were measured in conscious, chronically instrumented lambs aged ~1 (8±2 days, N=8) and 6 weeks (41±4 days, N=11). In each animal, measurements were made before and after administration of the selective AT1R antagonist ZD 7155 (experiment one) and the selective AT2R antagonist PD123319 (experiment two) as well as both antagonists, ZD 7155 and PD 123319 (experiment three). Results: Haemodynamic responses to combined inhibition of both AT1Rs and AT2Rs were similar to inhibition of AT1Rs alone: there was a significant decrease in SAP, DAP, and MAP and a significant increase in RBF within minutes of concomitant administration of ZD 7155 and PD 123319 in both age groups. These responses were similar to responses to ZD 7155 alone, whereas PD 123319 alone did not alter any of the measured variables. Conclusions: AT2Rs do not counterbalance the pressor and renal vasoconstrictor effects elicited by activation of AT1Rs in the immediate newborn period. During this time, AT1Rs appear to predominate in eliciting the haemodynamic effects of angiotensin II (ANG II), whereas the role of the upregulated AT2Rs remains elusive.

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Angiotensin II type 2 receptor-mediated vasodilation. Focus on bradykinin, NO and endothelium-derived hyperpolarizing factor(s)

Cited by 41 publications

References 76 publications

Developmental acceleration of bradykinin-dependent relaxation by prenatal chronic hypoxia impedes normal development after birth

Developmental acceleration of bradykinin-dependent relaxation by prenatal chronic hypoxia impedes normal development after birth

Defining the differential sensitivity to norepinephrine and angiotensin II in the ovine uterine vasculature

Do Angiotensin Type 2 Receptors Modulate Haemodynamic Effects of Type 1 Receptors in Conscious Newborn Lambs?

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