SUMMARY To assess the physiological role of atrial natriuretic factors in blood pressure regulation, we studied the effect of chronic infusion of a synthetic atrial natriuretic factor of 25 amino acid residues (Arg 102-Tyr 126) in rats with angiotensin H-induced hypertension. Rats were studied while on a normal sodium diet or during sodium loading with 1% NaCl solution used as drinking water. Systolic blood pressure decreased slightly during combined infusion of synthetic atrial natriuretic factor, 150 ju.g/kg/day, and angiotensin II, 900 /xg/kg/day. This effect was sustained for 3 days in rats receiving a regular sodium intake (p<0.01) and during sodium loading (p<0.01). Administration of synthetic atrial natriuretic factor to rats made hypertensive by a 3-day infusion of angiotensin II reduced blood pressure slightly, but not to control levels, and this effect was sustained for the remaining 3 days of the experiment in both dietary groups. These results indicate that a nonhypotensive dose of synthetic atrial natriuretic factor can modulate the vasopressor effect of angiotensin II. Thus, the attenuating effect may be involved in blood pressure regulation independently of sodium metabolism, although its actual physiological importance remains undetermined. (Hypertension 8: 748-753, 1986) KEY WORDS angiotensin II rat atrial natriuretic factor vascular smooth muscle blood pressure • sodium-water excretion A TRIAL natriuretic factor (ANF) is a potent na-/ \ triuretic and diuretic substance present in spe-X \~ cific granules of mammalian atrial cardiocytes.12 It can also relax isolated vascular smooth muscle and antagonize the vasoconstrictive actions of norepinephrine (NE) and angiotensin II (ANG II) in vitro.3 4 The natriuretic and vasorelaxant effects of ANF prompted us to investigate its possible role in the regulation of blood pressure, although its physiological relevance to blood pressure regulation has not been well documented.Since recent, extensive efforts have succeeded in purifying, sequencing, and synthesizing ANF, 5 " 9 more precise investigation of the vascular and renal actions of these peptides has become possible. Recently, by using ANF of 25 amino acid residues (Arg 102-Tyr 126) synthesized by Sugiyama et al. 10 and proven to have the same chemical characteristics and biological activities as natural ANF extracted from rat atrium and sequenced by Misono et al.,9 we demonstrated that a nonhypotensive dose of synthetic ANF inhibits the hypertension induced by chronic NE infusion in conscious rats."In the present study, we tried to evaluate the effect of chronic infusion of a synthetic ANF of 25 amino acid residues in conscious rats made hypertensive by chronic ANG II infusion. Materials and MethodsMale Sprague-Dawley rats (Charles River Japan, Atsagi, Japan) weighing 150 to 250 g were used. All rats were maintained in a room controlled for humidity and temperature. Throughout the study, each rat was housed in a metabolic cage designed to prevent fecesurine contact (Model ST; Sugiyamagen, Tokyo, J...

SUMMARY To elucidate the molecular mechanism of the vascular action of atrial natriuretic factor (ANF), we investigated the effects of synthetic ANF and sodium nitroprusside on the levels of intracellular cyclic nucleotides and prostacyclin (measured as its stable metabolite 6-keto-prostaglandin F,a) in cultured vascular smooth muscle cells from rat mesenteric artery and, in some experiments, from rat renal artery. Both ANF and sodium nitroprusside increased intracellular cyclic guanosine 3',5'-monophosphate (cGMP) levels in a dose-dependent manner but did not affect cyclic adenosine 3',5'-monophosphate levels or 6-keto-prostaglandin F, tt synthesis. The stimulatory effects of ANF and sodium nitroprusside on cGMP levels were additive. Neither the deprivation of extracellular Ca

SUMMARYWe have previously reported that captopril stimulates thromboxane A 2 synthesis in patients with essential hypertension. In the present study, the hypotensive effects of captopril and OKY-046, a selective inhibitor of thromboxane A 2 synthetase, were studied in nine patients with essential hypertension to determine whether thromboxane A 3 is involved in the regulation of blood

To assess possible roles of atrial natriuretic factor (ANF) in the regulation of blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats, we performed two series of experiments. First, we studied acute hypotensive, and natriuretic and diuretic effects of ANF in pentobarbital-anesthetized DOCA-salt hypertensive rats and age-matched controls. A synthetic rat ANF was intravenously administered as a bolus at doses of 0.5, 2.5 and 5.0 pg/kg. In DOCA-salt rats, a significant decrease in mean arterial pressure was observed at a dose of 5.0 pg/kg, whereas at a dose of 2.5 pg/kg in control rats. On the other hand, the diuretic and natriuretic effects of ANF were observed at a dose of 2.5 pg/ kg in DOCA-salt rats and 5.0pg/kg in control rats. Second, we examined chronic effect of ANF on the development of hypertension in DOCA-salt rats. The DOCA-salt rats, given 1% NaCI solution for drinking, were continuously infused with ANF (15, 75 and 150 pg/kg/day) or vehicle (physiological saline) into the jugular vein by osmotic minipumps for up to 14 days. In DOCA-salt treated rats, ANF at doses of 75 and 150pg/kg/day attenuated significantly the development of hypertension, although ANF at a dose of 15 p g/kg/day did not. The hypotensive effect of ANF was sustained throughout the experimental period and the effect of ANF at a dose of 150 p g/kg/day was more prominent than that of this peptide at a dose of 75 p g/kg/day. ANF did not induce any significant changes in urine volume, fluid intake and urinary excretion of sodium and potassium in DOCA-salt rats when compared to those in vehicle-infused DOCA-salt rats. These results indicate that DOCA-salt rats are more sensitive to ANF in diuretic and natriuretic effects, and less sensitive to ANF in hypotensive effect compared to control rats.