Synthetic Atrial Natriuretic Factor in Conscious Normotensive and Hypertensive Rats

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1985-05, Vol.7 (3 Suppl I), p.I-35-I-42
• Main Authors: SEYMOUR, ANDREA A, MARSH, ELIZABETH A, MAZACK, ELAINE K, STABILITO, INEZ I, BLAINE, EDWARD H
• Format: Article
• Language: English
• Subjects: Animals; Atrial Natriuretic Factor; Blood Pressure - drug effects; Cyclic GMP - urine; Hypertension - physiopathology; Hypertension, Renovascular - physiopathology; Male; Muscle Proteins - pharmacology; Rats; Rats, Inbred Strains; Sodium - urine; Urine
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.7.3_Pt_2.I35

Synthetic atrial natriuretic factor (Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-GIy-Leu-Gly-Cys-Asn-Ser-Phe-Arg-TVr-COOH [disulfide bond between cysteines]) was infused intravenously into conscious normotensive and deoxycorticosterone, onekidney, one-clip, and two-kidney, one-clip hypertensive rats. Mean arterial pressure, urine volume, and electrolyte excretion rates were measured during a 20-minute infusion of a single dose (ranging from 0–1520 pmol/min) into each animal; 95 to 380 pmol/minute of synthetic atrial natriuretic factor maximally reduced mean arterial pressure by −20 ± 4, −29 ± 2, and — 39 ± 7 mm Hg in normotensive, one-kidney, one-clip, and two-kidney, one-clip hypertensive rats, respectively. In deoxycorticosterone rats, a dose of 760 pmol/minute was required to produce the largest depressor response (−58 ± 12 mm Hg). Sodium excretion increased to 8.8 ± 2.5 μEq/minute at 760 pmol/minute in normotensive rats, to 6.5 ±1.1 μEq/minute at 50 pmol/minute in deoxycorticosterone rats, and to 5.8 ± 1.5 μEq/minute at 95 pmol/minute in one-kidney, one-clip animals. The natriuretic effect was consistently greater at all doses of synthetic atrial natriuretic factor in the two-kidney, one-clip hypertensive model, in which the maximum response was 15.3 ± 4.7 μEq/minute at 190 pmol/minute. The changes in urine volume and excretion rates of potassium and chloride tended to parallel the increases in sodium excretion in each model. Interestingly, the maximally effective hypotensive dose of synthetic atrial natriuretic factor was different from the maximally effective natriuretic dose in all four groups. Even though its exact mechanisms of action remain unclear, synthetic atrial natriuretic factor appears to be an effective hypotensive and natriuretic agent in several models of conscious hypertensive rats.