SUMMARY Synthetic atrial natriuretic factor (Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-AspArg-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 ^tEq/minute at 760 pmol/minute in normotensive rats, to 6.5 ± 1 . 1 /xEq/minute at 50 pmol/minute in deoxycorticosterone rats, and to 5.8 ± 1 . 5 /xEq/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 /xEq/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. 1 described the biological actions of atnal extracts in anesthetized rats and reported that atnal natriuretic factor (ANF) induced a natriuretic and a hypotensive response. Shortly thereafter, a direct vasorelaxant effect of atrial preparations was demonstrated in isolated vascular smooth muscle strips.2 "* In addition, urinary guanosine cyclic 3',5'-monophosphate (cGMP) excretion and plasma cGMP concentration were elevated following injection of atrial extracts in anesthetized rats.3 A closely related group of active peptides was later isolated from rat 6 " 11 and human 12 atria, and a peptide containing a 26 amino acid sequence was synthesized l3 The structure of the synthetic ANF is as follows: Arg-Arg-Ser-Ser-CysPhe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-
Atrial natriuretic factor (ANF) is a potent natriuretic and vasorelaxant agent that also stimulates guanosine 3',5'-cyclic monophosphate (cGMP) excretion in normotensive animals. These properties suggest that ANF may be involved in the regulation of blood pressure. To test a pure preparation of ANF in both normotensive and hypertensive animals, a synthetic 26 amino acid peptide (sANF) contained within endogenous rat ANF was infused intravenously into conscious Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) at doses from 12 to 190 pmol/minute. Mean arterial pressure fell progressively as doses of sANF were increased until maximum responses of -41 +/- 5 mm Hg and -29 +/- 5 mm Hg were obtained during infusion of 95 pmol/minute sANF in SHR and WKY, respectively. Heart rate was not significantly affected in either group. At sANF doses of 12 to 50 pmol/minute, urinary electrolyte excretion rose in a dose-related fashion and was similar in WKY and SHR. At infusions of 95 to 190 pmol/minute, the diuretic and saluretic responses were diminished in the hypertensive animals. Only the 190 pmol/minute sANF dose significantly enhanced cGMP excretion in SHR (p less than 0.05); however, in WKY urinary cGMP excretion was elevated in a dose-related fashion. At the highest sANF dose, cGMP excretion was approximately 15 times that observed in the pretreatment urine. The differences in the renal and blood pressure responses to sANF in SHR and WKY suggest that the actions of endogenous ANF may be altered in hypertension.
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