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

Vinturache AE, Smith FG - BMC Physiol. (2016)

Bottom Line: PD 123319 had no significant effects on glomerular filtration rate and tubular function in either age group.These 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology & Pharmacology; Alberta Children's Hospital Research Institute for Child and Maternal Health, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive, NW, Calgary, AB, T2N 4N1, Canada. aevintur@ucalgary.ca.

ABSTRACT

Background: Evidence 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.

Methods: The 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.

Results: ZD 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.

Conclusions: These 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.

No MeSH data available.


Related in: MedlinePlus

Effects of AT2R antagonist PD 123319 on tubular function in conscious lambs. Effects of AT2R antagonist, PD 123319 on urinary Na+ excretion rate (UNaV, panel a), urinary K+ excretion rate (UKV, panel c), urinary flow rate (V, panel b), and urine osmolality (UOsm, panel d) in conscious lambs aged ~ one week (open bars) and ~ six week (closed, gray shaded bars) measured before (Control, c) and for 60 min after intravenous infusion of ZD 7155. *p < 0.001 compared to c; †p < 0.05 compared to one week
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Fig3: Effects of AT2R antagonist PD 123319 on tubular function in conscious lambs. Effects of AT2R antagonist, PD 123319 on urinary Na+ excretion rate (UNaV, panel a), urinary K+ excretion rate (UKV, panel c), urinary flow rate (V, panel b), and urine osmolality (UOsm, panel d) in conscious lambs aged ~ one week (open bars) and ~ six week (closed, gray shaded bars) measured before (Control, c) and for 60 min after intravenous infusion of ZD 7155. *p < 0.001 compared to c; †p < 0.05 compared to one week

Mentions: The AT2R antagonist, PD 123319 had no significant effects on systemic and renal haemodynamics in either group of animals (Additional file 1: Table S1). There were also no changes in RPF, GFR or FF after infusion of PD 123319 (Fig. 1) in either age group. Also, no changes were observed in urine production (Fig. 3) and electrolyte excretion rates of Na+, K+, (Fig. 3) and Cl− (Table 3) after PD 123319 at one and six weeks. PD 123319 infusion did not alter reabsorption rates and clearances of electrolytes, urine osmolality nor osmolar clearance (Table 3).Fig. 3


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

Vinturache AE, Smith FG - BMC Physiol. (2016)

Effects of AT2R antagonist PD 123319 on tubular function in conscious lambs. Effects of AT2R antagonist, PD 123319 on urinary Na+ excretion rate (UNaV, panel a), urinary K+ excretion rate (UKV, panel c), urinary flow rate (V, panel b), and urine osmolality (UOsm, panel d) in conscious lambs aged ~ one week (open bars) and ~ six week (closed, gray shaded bars) measured before (Control, c) and for 60 min after intravenous infusion of ZD 7155. *p < 0.001 compared to c; †p < 0.05 compared to one week
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835895&req=5

Fig3: Effects of AT2R antagonist PD 123319 on tubular function in conscious lambs. Effects of AT2R antagonist, PD 123319 on urinary Na+ excretion rate (UNaV, panel a), urinary K+ excretion rate (UKV, panel c), urinary flow rate (V, panel b), and urine osmolality (UOsm, panel d) in conscious lambs aged ~ one week (open bars) and ~ six week (closed, gray shaded bars) measured before (Control, c) and for 60 min after intravenous infusion of ZD 7155. *p < 0.001 compared to c; †p < 0.05 compared to one week
Mentions: The AT2R antagonist, PD 123319 had no significant effects on systemic and renal haemodynamics in either group of animals (Additional file 1: Table S1). There were also no changes in RPF, GFR or FF after infusion of PD 123319 (Fig. 1) in either age group. Also, no changes were observed in urine production (Fig. 3) and electrolyte excretion rates of Na+, K+, (Fig. 3) and Cl− (Table 3) after PD 123319 at one and six weeks. PD 123319 infusion did not alter reabsorption rates and clearances of electrolytes, urine osmolality nor osmolar clearance (Table 3).Fig. 3

Bottom Line: PD 123319 had no significant effects on glomerular filtration rate and tubular function in either age group.These 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology & Pharmacology; Alberta Children's Hospital Research Institute for Child and Maternal Health, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive, NW, Calgary, AB, T2N 4N1, Canada. aevintur@ucalgary.ca.

ABSTRACT

Background: Evidence 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.

Methods: The 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.

Results: ZD 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.

Conclusions: These 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.

No MeSH data available.


Related in: MedlinePlus