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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 AT1R antagonist, ZD 7155 on tubular function in conscious lambs. Effects of AT1R antagonist, ZD 7155, 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, striped line 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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Fig2: Effects of AT1R antagonist, ZD 7155 on tubular function in conscious lambs. Effects of AT1R antagonist, ZD 7155, 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, striped line 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: Whereas UNaV was not influenced by the ZD 7155 treatment in either age group (Fig. 2), effects on K+ excretion were age-dependent (F = 8.391, p = 0.001): ZD 7155 significantly decreased UKV in younger animals, from 0.62 ± 0.32 to 0.28 ± 0.22 μmol · min−1 · g−1 but not in older ones (Fig. 2). This was accompanied by a decrease in TTKG by almost 30 % in younger lambs (p < 0.001) (Table 2). There was a trend towards an increase in the UNa/UK ratio after ZD 7155 infusion at one week but not six weeks (p = 0.08). There were no significant effects of the AT1R antagonist on Na+ and K+ reabsorption rates or CK in both groups of lambs (Table 2). CNa was altered by the infusion of ZD 7155 in an age-dependent manner: CNa increased in six but not one week old lambs (F = 28.577, p < 0.001).Fig. 2


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 AT1R antagonist, ZD 7155 on tubular function in conscious lambs. Effects of AT1R antagonist, ZD 7155, 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, striped line 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

Fig2: Effects of AT1R antagonist, ZD 7155 on tubular function in conscious lambs. Effects of AT1R antagonist, ZD 7155, 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, striped line 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: Whereas UNaV was not influenced by the ZD 7155 treatment in either age group (Fig. 2), effects on K+ excretion were age-dependent (F = 8.391, p = 0.001): ZD 7155 significantly decreased UKV in younger animals, from 0.62 ± 0.32 to 0.28 ± 0.22 μmol · min−1 · g−1 but not in older ones (Fig. 2). This was accompanied by a decrease in TTKG by almost 30 % in younger lambs (p < 0.001) (Table 2). There was a trend towards an increase in the UNa/UK ratio after ZD 7155 infusion at one week but not six weeks (p = 0.08). There were no significant effects of the AT1R antagonist on Na+ and K+ reabsorption rates or CK in both groups of lambs (Table 2). CNa was altered by the infusion of ZD 7155 in an age-dependent manner: CNa increased in six but not one week old lambs (F = 28.577, p < 0.001).Fig. 2

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