AT1 receptor expression in glomeruli from NO-deficient rats

Area of Science:

• Nephrology
• Cardiovascular Physiology
• Biochemistry

Background:

• Chronic nitric oxide synthase inhibition induces renin-dependent hypertension and renal injury.
• The role of renal angiotensin II receptors in this hypertensive model requires elucidation.

Purpose of the Study:

• To investigate the expression of renal angiotensin II type 1 (AT1) receptors in a rat model of chronic nitric oxide synthase inhibition.
• To determine the impact of nitric oxide deficiency and local angiotensin II concentration on AT1 receptor expression and function.

Main Methods:

• Rats were treated with N(G)-nitro-L-arginine methyl ester (L-NAME) for 1 month, with or without captopril.
• 125I-[Sar1, Ile8]-Ang II binding, AT1 mRNA expression, and cytosolic calcium levels were measured in isolated glomeruli and cultured mesangial cells.
• Angiotensin-converting enzyme activity and angiotensin II concentration were assessed in renal cortex.

Main Results:

• L-NAME treatment caused significant renal injury.
• AT1 receptor number and mRNA expression were decreased in L-NAME-treated rats, an effect reversed by captopril.
• Reduced AT1 receptor expression correlated with an attenuated cytosolic calcium response to angiotensin II.
• Angiotensin-converting enzyme activity and renal angiotensin II levels were elevated in L-NAME rats.
• In vitro, nitric oxide donor treatment decreased AT1 receptor binding, mRNA, and calcium response.

Conclusions:

• The downregulation of AT1 receptors in this model is primarily due to elevated local angiotensin II concentrations resulting from stimulated angiotensin-converting enzyme activity, not a direct effect of nitric oxide deficiency.
• The observed renin-angiotensin system activation in this hypertension model does not stem from AT1 receptor overexpression.