Effect of atrial natriuretic factor on angiotensin II-induced hypertension in rats.

Abstract

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...

Blood pressure and renal responses to synthetic rat atrial natriuretic factor in deoxycorticosterone acetate-salt hypertension.

“…Therefore it may be assumed that the hypotensive response in DOCA-salt rats may not be due to a circulatory volume contraction via its renal effects, but due to its direct vascular effects. That the hypotensive effect of ANF appears to be related to a direct vasodilation-effect is not surprizing because recent studies have reported that similar effect of ANF was observed in conscious rats made hypertensive by chronic infusion of norepinephrine (Yasujima et al 1985), angiotensin II (Yasujima et al 1986a) or vasopressin (Yasujima et al 1986b), or in conscious two-kidney, one clip hypertensive rats (Garcia et al 1985), or conscious young SHR ).…”

“…Recently, in vivo studies, we have shown that chronic infusion of a nonhypotensive dose of synthetic ANF (150 ,u g/kg/day) attenuated the hypertensive effect of chronic infusion of norepinephrine (Yasujima et al 1985), angiotensin II (Yasujima et al 1986a) or vasopressin (Yasujima et al 1986b) in conscious rats and that the antihypertensive effect was independent of renal effects of this peptide. In addition, we have also shown that chronic infusion of the same dose of a synthetic ANF did not affect the development of hypertension in young SHR on normal sodium diet or on sodium loading with 1% NaCI solutions in place of drinking water ).…”

An update on the physiology of atrial natriuretic factor.

“…Higher doses of ANF (40-100 ng-min"'-kg-1 ) infused for 3 to 7 days were hypotensive but not natriuretic in the following rat models of hypertension: twokidney, one clip 31 ; angiotensin U-infused 32 ; and norepinephrine-infused. 33 Although it is unclear whether these doses mimicked physiological, pathological, or pharmacological blood levels of ANF, the following information can be gleaned from these studies.…”

“…A 3-day infusion of ANF completely reversed the hypertension caused by norepinephrine infusion, 33 yet only slightly lowered arterial pressure in angiotensin U-infused rats. 32 However, this does not indicate that ANF is more effective at reversing the effects of the sympathetic nervous system than those of the renin-angiotensin system. It may be quite effective at inhibiting renin release and thus may have a profound influence on this system under more natural conditions.…”

Effects of digoxin on blood pressure responses to norepinephrine, angiotensin II and vasopressin in conscious rats.

“…[Ile5] angiotensin II and [Arg8] vasopressin (Protein Research Foundation, Osaka) were dissolved in 0.01 N acetic acid and were delivered at a rate of 900 p g/kg/day and at a rate of 7.2 U/kg/day, respectively. Chronic infusion of NE, A II or VP at this dose has been shown to induce a sustained increase in systolic blood pressure (Yasujima et al 1984(Yasujima et al , 1985(Yasujima et al , 1986a.…”