The subtype 2 of angiotensin II receptors and pressure-natriuresis in adult rat kidneys

Abstract

The present work examined the effects of the subtype 2 of angiotensin II (AT2) receptors on the pressure-natriuresis using a new peptide agonist, and the possible involvement of cyclic guanosine 3', 5' monophosphate (cyclic GMP) in these effects. In adult anaesthetized rats (Inactin, 100 mg kg(-1), i.p.) deprived of endogenous angiotensin II by angiotensin converting enzyme inhibition (quinapril, 10 mg kg(-1), i.v.), T2-(Ang II 4-8)2 (TA), a highly specific AT2 receptor agonist (5, 10 and 30 microg kg(-1) min(-1), i.v.) or its solvent was infused in four groups. Renal functions were studied at renal perfusion pressures (RPP) of 90, 110 and 130 mmHg and urinary cyclic GMP excretion when RPP was at 130 mmHg. The effects of TA (10 microg kg(-1) min(-1)) were reassessed in animals pretreated with PD 123319 (PD, 50 microg kg(-1) min(-1), i.v.), an AT2 receptor antagonist and the action of the same dose of PD alone was also determined. Increases in RPP from 90 to 130 mmHg did not change renal blood flow (RBF) but induced 8 and 15 fold increases in urinary flow and sodium excretion respectively. The 5 microg kg(-1) min(-1) dose of TA was devoid of action. The 10 and 30 microg kg(-1) min(-1) doses did not alter total RBF and glomerular filtration rate, but blunted pressure-diuresis and natriuresis relationships. These effects were abolished by PD. TA decreased urinary cyclic GMP excretion. After pretreatment with PD, this decrease was reversed to an increase which was also observed in animals receiving PD alone. In conclusion, renal AT2 receptors oppose the sodium and water excretion induced by acute increases in blood pressure and this action cannot be directly explained by changes in cyclic GMP.

Figure 1

Averaged values (n=5) of mean blood pressure (MBP) and renal blood flow (RBF) in response to angiotensin I (AI) injections (750 ng kg⁻¹) before, 30, 60, 90 and 120 min after angiotensin converting enzyme inhibition by quinapril (10 mg kg⁻¹).

Figure 2

Effects of TA on the relationships between renal perfusion pressure (RPP), renal blood flow (RBF), glomerular filtration rate (GFR), urine flow (V) and sodium excretion (UNaV) in rats deprived of endogenous angiotensin II and infused with solvent (Controls) or TA at the doses of 5, 10 or 30 μg kg⁻¹ min⁻¹ (TA-5, TA-10 and TA-30).

Figure 3

Effects of renal perfusion pressure (RPP) on renal blood flow (RBF), glomerular filtration rate (GFR), urine flow (V) and sodium excretion (UNaV) in rats deprived of endogenous angiotensin II and infused with solvent (Controls) or TA (10 μg kg⁻¹ min⁻¹, TA-10) or PD 123319 (50 μg kg⁻¹ min⁻¹, PD) or PD 123319 combined to TA (PD+TA-10).

Figure 4

Urinary excretion of cyclic guanosine 3′, 5′ monophosphate (cyclic GMP) in rats deprived of endogenous angiotensin II and infused with solvent (Controls) or TA (10 μg kg⁻¹ min⁻¹, TA-10) or PD 123319 (50 μg kg⁻¹ min⁻¹, PD) or PD 123319 combined to TA (PD+TA-10). The renal perfusion pressure was set at 130 mmHg. ^*P<0.05 vs controls; ^†P<0.05, ^††P<0.01 vs TA-10.