Angiotensin receptors modulate the renal hemodynamic effects of nitric oxide in conscious newborn lambs

Vinturache, Angela; Smith, Francine G.

doi:10.14814/phy2.12027

Cited by 5 publications

(2 citation statements)

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“…Based on the distinct pattern of ATRs distribution in the developing kidney in several species, including porcine, ovine and primate kidney [ 6 , 29 , 30 , 41 , 49 , 56 , 57 , 61 , 63 ], we hypothesised that immediately after birth activation of AT2Rs may contribute to the adaptation of glomerular function in the immediate newborn period. This was not the case.…”

Section: Discussionmentioning

confidence: 99%

“…For example, AT1R inhibition may have revealed the role of other vasoactive factors, such as prostaglandins, bradykinin, or nitric oxide. Previously, we have reported that the renal haemodynamic effects of nitric oxide are regulated by Ang II through activation of both ATRs [ 57 , 60 ] in an age-dependent manner, with AT2Rs being a more important regulator of renal haemodynamics in the newborn and AT1Rs more predominant later in life [ 57 ]. Also, pre-treatment with the cyclooxygenase inhibitor, indomethacin, augments the pressor response to Ang II and modulates the vasomotor effect of Ang II in response to infusion of the nitric oxide inhibitor, L-NAME, thus removing endogenously produced nitric oxide [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

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Renal effects of angiotensin II in the newborn period: role of type 1 and type 2 receptors

Vinturache

Smith

2016

BMC Physiol

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BackgroundEvidence suggests a critical role for the renin-angiotensin system in regulating renal function during postnatal development. However, the physiological relevance of a highly elevated renin-angiotensin system early in life is not well understood, nor which angiotensin receptors might be involved. This study was designed to investigate the roles of angiotensin receptors type 1 (AT1R) and type 2 (AT2R) in regulating glomerular and tubular function during postnatal development.MethodsThe renal effects of the selective antagonist to AT1R, ZD 7155 and to AT2R, PD 1233319 were evaluated in two groups of conscious chronically instrumented lambs aged ~ one week (N = 8) and ~ six weeks (N = 10). Two experiments were carried out in each animal and consisted of the assessment of renal variables including glomerular and tubular function, for 30 min before (Control) and 60 min after infusion of ZD 7155 and PD 123319, respectively. Statistical significance was determined using parametric testing (Student t-test, analysis of variance ANOVA) as appropriate.ResultsZD 7155 infusion was associated with a significant decrease in glomerular filtration rate and filtration fraction at one but not six weeks; urinary flow rate decreased significantly in older animals, whereas sodium excretion and free water clearance were not altered. There was an age-dependent effect on potassium handling along the nephron, potassium excretion decreasing after ZD 7155 infusion in younger but not in older lambs. PD 123319 had no significant effects on glomerular filtration rate and tubular function in either age group.ConclusionsThese results provide evidence to support an important role for AT1Rs in mediating the renal effects of angiotensin II during postnatal maturation in conscious developing animals. In contrast to a role for AT2Rs later in life, there appears to be no role for AT2Rs in influencing the renal effects of Angiotensin II in the postnatal period.Electronic supplementary materialThe online version of this article (doi:10.1186/s12899-016-0022-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Renal effects of angiotensin II in the newborn period: role of type 1 and type 2 receptors

Vinturache

Smith

2016

BMC Physiol

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Glomerular and tubular effects of nitric oxide (NO) are regulated by angiotensin II (Ang II) in an age-dependent manner through activation of both angiotensin receptors (AT1Rs and AT2Rs) in conscious lambs

Vinturache

Smith

2017

Pflugers Arch - Eur J Physiol

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Renin-angiotensin (RAS) and nitric oxide (NO) systems and the balance and interaction between them are considered of primary importance in maintaining fluid and electrolyte homeostasis. It has been suggested that the effects of NO may be modulated at least in part by the angiotensin (Ang) II, yet the roles of angiotensin receptor type 1 (AT1R) and type 2 (AT2R) are not well understood. Even though both Ang II and NO are elevated at birth and during the newborn period, their contribution to the adaptation of the newborn to life after birth as well as their physiological roles during development are poorly understood. The aim of this study was to determine if NO regulation of renal function during postnatal maturation is modulated by Ang II through activation of AT1R or AT2R or both receptors. Glomerular and tubular effects of either AT1R selective antagonist ZD 7155, AT2R selective antagonist PD 123319, and both antagonists ZD 7155 plus PD 123319, were measured in 1- (N = 9) and 6-week-old (N = 13) conscious, chronically instrumented lambs before and after removal of endogenous NO with L-arginine analogue, L-NAME. Two-way analysis of variance (ANOVA) procedures for repeated measures over time with factors age and treatment were used to compare the effects of the treatments on several glomerular and tubular variables in both groups. This study showed that L-NAME infusion after pre-treatment with ATR antagonists did not alter glomerular function in 1- or 6-week-old lambs. NO effects on electrolytes handling along the nephron during postnatal development were modulated by Ang II through AT1R and AT2R in an age-dependent manner. Selective inhibition of AT1R and AT2R increased excretion of Na, K, and Cl in 6- but not in 1-week-old lambs. In 6-week-old lambs, urinary flow rate increased by 200%, free water clearance increased by 50%, and urine osmolality decreased by 40% after L-NAME was added to the pre-treatment with ZD 7155 plus PD 123319. When L-NAME was added either to ZD 7155 or PD 123319, the same trend in the alterations of these variables was observed, albeit to a lower degree. In conclusion, in conscious animals, during postnatal maturation, Ang II modulates the effects of NO on glomerular function, fluid, and electrolyte homeostasis through AT1Rs and AT2Rs in an age-dependent manner. Under physiological conditions, AT2Rs may potentiate the effects of AT1R, providing evidence of a crosstalk between ATRs in modulating NO effects on fluid and electrolyte homeostasis during postnatal maturation. This study provides new insights on the regulation of renal function during early postnatal development showing that, compared with later in life, newborns have impaired capacity to regulate glomerular function, water, and electrolyte balance.

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Development of the Renin-Angiotensin System

Smith¹

2017

Fetal and Neonatal Physiology

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Angiotensin receptors modulate the renal hemodynamic effects of nitric oxide in conscious newborn lambs

Cited by 5 publications

References 59 publications

Renal effects of angiotensin II in the newborn period: role of type 1 and type 2 receptors

Renal effects of angiotensin II in the newborn period: role of type 1 and type 2 receptors

Glomerular and tubular effects of nitric oxide (NO) are regulated by angiotensin II (Ang II) in an age-dependent manner through activation of both angiotensin receptors (AT1Rs and AT2Rs) in conscious lambs

Development of the Renin-Angiotensin System

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