Effect of interactions between nitric oxide and angiotensin II on pressure diuresis and natriuresis.
The present study examined the effect of an angiotensin II AT1 or AT2 receptor antagonist on the impairment of the pressure diuresis and natriuresis response produced by nitric oxide (NO) synthesis blockade. N omega-nitro-L-arginine methyl ester (L-NAME, 37 nmol.kg-1.min-1) lowered renal blood flow and reduced the slopes of the pressure diuresis and natriuresis responses by 44 and 40%, respectively. Blockade of AT1 receptors with valsartan increased slightly sodium and water excretion at low renal perfusion pressure (RPP). Blockade of AT2 receptors with PD-123319 had no effect on renal function. The administration of valsartan or PD-123319 to rats given L-NAME had no effect on the renal vasoconstriction induced by NO synthesis blockade. In addition, in rats given L-NAME, valsartan elevated baseline excretory values at all RPP studied, but it had no effect on the sensitivity of the pressure diuresis and natriuresis response. However, the administration of PD-123319 to L-NAME-pretreated rats shifted the slopes of the pressure diuresis and natriuresis responses toward control values, indicating that the impairment produced by NO synthesis blockade on pressure diuresis is dependent on the activation of AT2 angiotensin receptors.
Madrid
M I
MI
Departamento de Fisiología y Farmacología, Facultad de Medicina, Murcia, Spain.
García-Salom
M
M
Tornel
J
J
De Gasparo
M
M
Fenoy
F J
FJ
D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects / Q000502:physiology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D011312:Pressure; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D009569:Nitric Oxide; D000068756:Valsartan; D014633:Valine; D019331:NG-Nitroarginine Methyl Ester