Atrial Natriuretic Peptide in Chronically Hypertensive Dogs

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1995-10, Vol.26 (4), p.634-641
• Main Authors: Seymour, Andrea A, Asaad, Magdi M, Sheldon, Jeffrey H, Smith, Patricia L, Rogers, W. Lynn
• Format: Article
• Language: English
• Subjects: Alanine - analogs & derivatives; Alanine - pharmacology; Animals; Antihypertensive agents; Atrial Natriuretic Factor - pharmacology; Biological and medical sciences; Blood Pressure - drug effects; Cardiovascular system; Chronic Disease; Diuretics - pharmacology; Dogs; Female; Humans; Hypertension, Renovascular - physiopathology; Injections, Intravenous; Kidney - drug effects; Kidney - physiopathology; Male; Medical sciences; Neprilysin - antagonists & inhibitors; Peptide Fragments - pharmacology; Pharmacology. Drug treatments
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.26.4.634

We determined the renal and depressor activities of 10, 50, and 100 pmol/kg per minute IV of human atrial natriuretic peptide-(99-126) in conscious one-kidney, one clip dogs with chronic hypertension and modest renal dysfunction, as indicated by mild proteinuria. Atrial natriuretic peptide increased fractional sodium excretion by 0.009 plus/minus 0.002, 0.042 plus/minus 0.005, and 0.049 plus/minus 0.007, respectively; urinary excretion of atrial natriuretic peptide by -0.4 plus/minus 0.8, 3.3 plus/minus 1.4, and 15.8 plus/minus 7.4 fmol/min; and cGMP excretion by 0.65 plus/minus 0.06, 1.65 plus/minus 0.08, and 4.88 plus/minus 0.85 nmol/min in one-kidney shams. The changes in fractional sodium excretion were significantly attenuated in the hypertensive dogs (0.005 plus/minus 0.002, 0.018 plus/minus 0.003, and 0.022 plus/minus 0.004, respectively) despite exaggerated increases in atrial natriuretic peptide excretion (3.3 plus/minus 1.6, 22.0 plus/minus 5.0, and 46.6 plus/minus 10.8 fmol/min) and cGMP excretion (0.96 plus/minus 0.47, 4.51 plus/minus 1.27, and 7.06 plus/minus 1.38 nmol/min). The slope of the line relating urinary atrial natriuretic peptide to cGMP was significantly suppressed in the hypertensive dogs, suggesting a downregulation of the guanylate cyclase-linked receptors. The slope of the relationship between cGMP excretion and the natriuretic response was also depressed in the hypertensive dogs, indicating possible impairment of cGMP signal transduction. The differences between sham and hypertensive dogs were diminished when urinary levels of atrial natriuretic peptide were maximized by prior treatment with SQ 28603, an inhibitor of neutral endopeptidase EC 3.4.24.11. Atrial natriuretic peptide caused comparable decreases in mean arterial pressure and increases in glomerular filtration rate in sham and hypertensive dogs, suggesting similar vascular reactivity. In conclusion, dogs with chronic one-kidney, one clip hypertension and mild proteinuria were hyporesponsive to the renal activity of atrial natriuretic peptide, presumably because of renal receptor downregulation and possible defects in cGMP signal transduction. (Hypertension. 1995;26:634-641.)