Microvascular effects of atrial natriuretic peptide in rat cremaster

Experiments utilized the open cremaster preparation to test the hypothesis that atrial natriuretic peptide (ANP)-induced volume changes result from microvascular resistance alterations. Atrial natriuretic peptide (25, 100, and 500 ng/kg/min, IV) or vehicle was infused into anesthetized rats. At the two highest ANP infusion rates, mean arterial pressure was significantly reduced from 104 ± 3 (control) to 87 ± 2 and 77 ± 2 mmHg, respectively. Hematocrit was 41.0 ± 0.8 and 45.6 ± 0.9% (p < 0.05) at the end of vehicle and ANP infusions, respectively. Despite these effects of ANP, there were no significant arteriolar or venular diameter alterations. Thirty μM nitroprusside significantly dilated all vessel segments except large venules. These observations suggest that resistance alterations in the skeletal muscle microvasculature are not the cause of ANP-induced fluid movement.     

Renal hemodynamic and natriuretic effects of atrial natriuretic factor

In this article we review the renal hemodynamic and excretory actions of atrial natriuretic factor (ANF) and consider some of the mechanisms of its vascular and natriuretic effects. ANF leads to a marked, sustained, and parallel increase in whole-organ and superficial single-nephron glomerular filtration rate (GFR) while mean blood pressure is decreased and renal blood flow (RBF) is unchanged or even decreased. The increase in GFR is caused by an efferent arteriolar vasoconstriction or by a combination of afferent vasodilation and efferent vasoconstriction. ANF also leads to a decrease in the hypertonicity of the innermedullary interstitium. Together with the increase in GFR, this phenomenon accounts wholly or in great part for the ANF-induced natriuresis. The overall renal vascular effects of ANF are complex and may tentatively be conceptualized as a behavior of a functional partial agonist: slight vasoconstriction in vasodilated kidneys, no sustained effects on the vascular resistance in normal kidneys, and vasodilation in vasoconstricted kidneys. The vasoconstrictor effect of ANF may be direct or indirect and depends on extracellular calcium whereas the antagonist effect likely results from alterations in intracellular calcium homeostasis. The data raise the perspective that ANF is not only a powerful natriuretic substance but has the potential of being an important modulator of GFR and RBF in intact animals.     

Renal actions of atrial natriuretic peptide on the postischemic kidney

The objective of this study was to evaluate the renal actions of atrial natriuretic peptide (ANP) in the unilateral postischemic kidney of anesthetized dogs with a severe reduction in glomerular filtration rate. The dose of atrial natriuretic peptide (50 ng.kg-1.min-1) we gave did not alter the mean systemic arterial pressure, renal blood flow, and glomerular filtration rate in the normal kidney, as determined in foregoing studies. ANP was infused into the intrarenal artery continuously for 60 min after the release from 45 min of complete renal artery occlusion. In the vehicle-infused group, the glomerular filtration rate fell dramatically (6% of control), the renal blood flow decreased (60% of control), and the mean systemic arterial pressure tended to increase (136% of control). The urine flow rate and urinary excretion of sodium decreased significantly (25 and 25%, respectively) at 30 min after reflow in the postischemic period. Continuous renal artery infusion of ANP resulted in a marked increase in urine flow rate (246% of control) and the urinary excretion of sodium (286% of control). The administration of ANP led to an improvement in renal blood flow (99% of control) and glomerular filtration rate (40% of control), and attenuated the rise in mean systemic arterial pressure (109% of control), compared with findings in the vehicle-infused group. Plasma renin activity and prostaglandin E2 concentration in the renal venous blood were elevated after the release from complete renal artery occlusion in both groups. These results indicate that the vascular effects of ANP on the postischemic kidney were enhanced and that the peptide maintained the natriuretic effect.     

Diuretic, natriuretic and hypotensive effects of synthetic atrial natriuretic factor in conscious newborn calves

The effects of synthetic Atrial Natriuretic Factor (ANF) on urine flow rate, sodium excretion, potassium excretion and arterial blood pressure were studied in 10-12 days-old female calves. In four female calves fitted with a Foley catheter, an intravenous administration of ANF (Ile-ANF 26; 1.6 micrograms/kg body wt during 30 min) induced an increase (P less than 0.01) in urine flow rate (from 1.8 +/- 0.2 to 12.8 +/- 1.1 ml/min), sodium excretion (from 0.15 +/- 0.02 to 0.81 +/- 0.06 mmol/min) and free water clearance (from 0.13 +/- 0.9 to 5.16 +/- 0.5 ml/min). It had no significant effect on potassium excretion. In four calves chronically-instrumented with a carotid catheter, an intravenous administration of synthetic ANF alone (1.6 micrograms/kg body wt during 30 min) induced a gradual decrease (P less than 0.01) in systolic, diastolic and mean arterial blood pressure (from 112 +/- 4 to 72, from 72 +/- 2 to 61 +/- 1 and from 90 +/- 2 to 65 +/- 2 mmHg respectively, at the end of ANF infusion). An intravenous administration of angiotensin II (AII) (0.5 micrograms/kg body wt during 45 min) induced a significant increase in systolic, diastolic and mean arterial blood pressure which was antagonized by an i.v. bolus injection of ANF (0.125 micrograms/kg body wt). However, during a simultaneous administration of AII (0.3 micrograms/kg body wt during 30 min) and ANF (1.6 micrograms/kg body wt. during 30 min), the atrial peptide did not influence the pressure action of AII. These findings indicate that the conscious newborn calf is sensitive to diuretic, natriuretic and hypotensive effects of synthetic ANF.     

Plasma atrial natriuretic peptide in conscious rats with reduced renal mass

The effect of salt intake and reduction of renal mass (RRM) on plasma immunoreactive atrial natriuretic peptide (iANP) levels in conscious rats was studied. Rats were divided into RRM and sham-operated groups, and then further subdivided into groups infused with 1 or 6 mEq of sodium per day. Plasma urea nitrogen increased in the groups with RRM. Plasma sodium, sodium balance, and heart rate did not differ between the sham and RRM groups. Rats with RRM maintained on 1 mEq of sodium per day did not have an elevation of water intake, arterial pressure, or plasma iANP. Rats with RRM maintained on 6 mEq of sodium per day had significantly (P less than 0.05) elevated water intake, arterial pressure, and plasma iANP. Arterial pressure and plasma iANP were correlated (r = 0.800) for rats with RRM on either 1 or 6 mEq of sodium per day. Increased plasma iANP in the RRM group on 6 mEq per day was not caused by either RRM or high sodium alone; it was an effect of RRM plus high salt intake. The increase in plasma iANP in the RRM group may be caused by the increase in arterial pressure, possibly due to an increase in extracellular fluid volume. ANP may not be responsible for the sustained increase in fractional sodium excretion observed in RRM.     

Four-hour atrial natriuretic peptide infusion in conscious rats: effects on urinary volume, sodium, and cyclic GMP

Atrial natriuretic peptide (ANP) is released from the cardiac atria in response to acute volume loads; when infused acutely ANP causes diuresis and natriuresis. Cyclic GMP (cGMP) appears to be the second messenger for ANP in the kidney. The role that ANP plays in the long-term regulation of salt and water balance is unclear, however, since resistance to ANP's natriuretic and diuretic activity develops during prolonged administration. The purpose of the present study is to examine the relationship between the rate of cGMP excretion in response to ANP and the development of resistance to ANP's diuretic and natriuretic activity. Following a 30-min baseline period of infusion of Ringer's solution conscious rats received ANP at 15 micrograms/kg/hr (n = 6) or Ringer's alone (n = 5) for 240 min. ANP-infused rats had a significant diuresis and natriuresis during the first hour of infusion; urinary cGMP excretion also increased compared to baseline. By 120 min after initiating the infusion in ANP-rats urinary volume and sodium excretion had declined to values not significantly different from those of baseline or control. In contrast, urinary cGMP excretion remained elevated for the duration of the ANP infusion, whether compared to baseline values or the control group. Resistance to the diuretic and natriuretic activity of ANP is not a result of mechanisms that involve cGMP generation.     

Renal effects of atrial natriuretic factor in domestic fowl

The renal hemodynamic and tubular effects of ANF were investigated using the Sperber technique in chickens. This technique takes advantage of the unique portal circulation of the avian kidney and permits direct access to the renal peritubular space independent of renal arterial blood flow and glomerular filtration. Infusion of ANF into the avian renal portal system increased urine flow rate and sodium excretion by as much as 300% and 100%, respectively. These changes occurred in the absence of significant alterations in glomerular filtration rate or renal plasma flow. There was no significant difference in urine flow, sodium excretion or glomerular filtration rate between the ANF-infused kidney and the contralateral, non-infused kidney. We conclude that the diuretic and natriuretic effects of ANF do not depend on changes in glomerular filtration rate and that the site of action of ANF is the renal medulla.     

Postmortem stability of the rat atrial natriuretic peptide in blood and atrial tissue

The postmortem stability of the rat Atrial Natriuretic Peptide (ANP) has been studied as a necessary and previous step to be applied in the forensic field as a postmortem marker. This peptide--whose extreme sensitivity to slight changes in blood volume is well known--could have great importance in thanatochemistry to establish a correct diagnosis when macroscopical observations and classical parameters are not conclusive or cannot be employed. The results show high stability in atrial tissue, where values are similar from 0 hours (108.99 pm/mg) to 8 hours (109.41 pm/mg) and decrease uniformly until 15 pm/mg) at 32 hours, time of our last determination. Blood ANP showed similar stability from 0 h (105.43 pg/ml) to 8 h (106.62 pg/ml).     

Cardiovascular and renal effects of eel and rat atrial natriuretic peptide in rainbow trout,Salmo gairdneri

Summary The renal and in vitro vascular effects of atrial natriuretic peptides have been examined in seveal species of fish. However, comparatively few investigations have described the effects of these peptides on the cardiovascular system in vivo. In the present experiments the dorsal aorta and urinary bladder were cannulated and the effects of atrial natriuretic peptides from rat and eel were monitored in conscious trout during bolus injection or continuous atrial natriuretic peptide infusion. The results show that the initial pressor effect of atrial natriuretic peptides is independent of environmental salinity adaptation (fresh or seawater) and the chemical form of atrial natriuretic peptide injected, but it is affected by the rate of atrial natriuretic peptide administration. This pressor response, and the accompanying diuresis, are mediated through -adrenergic activation. Continuous infusion of either rat or eel atrial natriuretic peptide produces a steady fall in mean arterial blood pressure, which is temporally preceded by an increase in heart rate and a decrease in pulse pressure. Diuresis induced by atrial natriuretic peptides is only partially sustained during continuous infusion. Propranolol partially blocks the increase induced in heart rate by atrial natriuretic peptides, but does not affect either pulse pressure or mean arterial pressure. Propranolol significantly increases urine flow in saline-infused animals but has no apparent effect on animals subjected to infusions of atrial natriuretic peptides. These results indicate that there are multiple foci for the action of atrial natriuretic peptides in trout and that in many instances the effects of atrial natriuretic peptides are mediated through secondary effector systems.Abbreviations ANP atrial natriuretic peptide - bw body weight - PBS phosphate-buffered saline     

The rat thymus--a site of atrial natriuretic peptide synthesis

The atrium of the heart has been demonstrated to represent the major site of synthesis of atrial natriuretic peptide (ANP), a potent natriuretic, diuretic and vasoactive hormone. Our recent studies revealed ANP-like material outside the heart, namely, in lymphoid follicles of the intestine and in the thymus, and now we report data demonstrating the thymus as a site of synthesis for ANP. The experimental evidence is as follows: firstly, the immunoreactive material detected corresponds chromatographically with the precursor of ANP. Secondly, the thymus contains mRNA for ANP. Thirdly, immunohistochemistry locates ANP-like material to cortical thymocytes with particularly dense staining in the subcapsular areas of the thymus. Interestingly, both ANP-like material and the mRNA coding for ANP were expressed to a larger extent in newborn rats as compared to adult animals, suggesting that ANP may be involved in the development and/or function of T-cells.     

Renal and systemic effects of synthetic atrial natriuretic factor

A synthetic peptide corresponding to a sequence of 26 amino acids contained in endogenous rat atrial natriuretic factor (ANF), was infused into one renal artery of anesthetized dogs for a comprehensive in vivo evaluation of the renal and systemic effects of pure ANF. The results proved conclusively that ANF acted directly on the kidney since urine volume and fractional excretion of sodium, potassium, chloride and calcium were elevated in a dose-related manner in the ANF-treated kidney, but were not significantly affected in the contralateral saline-infused organ. The maximum effects achieved with the synthetic ANF were higher than any reported following intravenous administration of crude extracts of rat atria and were similar to those produced by thiazide diuretics. In four of the five dogs studied, renal vascular resistance fell progressively as doses of ANF were increased. Glomerular filtration rate was not significantly elevated during ANF infusion, but was correlated with sodium excretion rates. Even though mean arterial pressure was progressively reduced, there was no significant change in heart rate and no stimulation of renin secretion. Arterial cyclic GMP concentration was higher in the basal state and rose more rapidly than did renal venous levels, indicating that increases in circulating concentrations of arterial cyclic GMP originated from an extrarenal source. Dose-related elevations in urinary cyclic GMP excretion could be explained by increased cyclic GMP filtration, by enhanced production in tubular cells, or by renal tubular secretion. Especially in the saline-infused kidney, there was a clear dissociation between excretion of cyclic GMP and fractional sodium excretion. We conclude that the synthetic ANF increased electrolyte excretion via a direct renal action which was not solely dependent upon changes in renal vasculature, renin secretion or cyclic GMP levels.     

The effects of intracerebroventricular infusion of atrial natriuretic factor in conscious sheep

The effects of 24-hour intracerebroventricular infusion of human atrial natriuretic factor (ANF) and two related fragments were studied in conscious sheep. ANF (1-28) had no effect on either mean arterial pressure (MAP) or heart rate (HR) when infused at 3 or 10 micrograms/hr, however a small diuresis and an increase in urinary sodium (Na) excretion was observed. The smaller fragment, ANF (5-27) infused at 10 micrograms/hr, increased MAP, HR and body temperature, although the same rate of infusion of ANF (5-28) was without effect. All peptides increased plasma sodium concentration and plasma osmolality. None of the peptides affected plasma ACTH, glucose or renin concentration. ANF (1-28) had no effect on either Na intake or water intake in Na-depleted sheep. These studies suggest that members of the ANF family can influence a number of physiological functions following central administration.     

Ovarian atrial natriuretic peptide during the rat estrous cycle.

The changes in ovarian levels of immunoreactive atrial natriuretic peptide (irANP) and arginine vasopressin (irAVP) were observed during the estrous cycle of rat. We also demonstrated the synthesis of ovarian ANP. In adult 4-day cycling rats, ovarian level of irANP was found to be the highest on proestrus and was to be the lowest on diestrus. Ovarian irANP level inversely correlated with ovarian level of irAVP. On reverse-phase HPLC, two distinct peaks of ovarian irANP, high and low molecular weight forms, existed in the each stage of the estrous cycle. However, no significant changes in plasma and atrial concentrations of ANP were observed during the cycle. The rat ovary contained mRNA coding for ANP. These data showing the synchronized cyclic change of ovarian irANP and irAVP with the estrous cycle suggest that the ovary locally synthesizes ANP and ovarian ANP may play regulatory roles on the follicular fluid dynamics.     

Brain natriuretic peptide interacts with atrial natriuretic peptide receptor in cultured rat vascular smooth muscle cells

The effect of synthetic porcine brain natriuretic peptide (pBNP), a novel brain peptide with sequence homology to alpha-human atrial natriuretic peptide (hANP), on receptor binding and cGMP generation, was studied in cultured rat vascular smooth muscle cells (VSMC) and compared with that of alpha-hANP. 125I-pBNP bound to the cells in a time-dependent manner similar to that of 125I-alpha-hANP. Scatchard analysis indicated a single class of binding sites for pBNP with affinity and capacity identical to those of alpha-hANP. pBNP and alpha-hANP were almost equipotent in inhibiting the binding of either radioligand and stimulating intracellular cGMP generation. These data indicate that BNP and ANP interact with the same receptor sites to activate guanylate cyclase in rat VSMC.     

利钾尿肽和心钠素在自发性高血压大鼠肾内的降解代谢

利钾尿肽 (ｋａｌｉｕｒｅｔｉｃｐｅｐｔｉｄｅ ,ＫＰ)是近年发现的与心钠素 (ａｔｒｉａｌｎａｔｒｉｕｒｅｔｉｃｐｅｐｔｉｄｅ ,ＡＮＰ)源于同一前体的具有 2 0个氨基酸的生物活性多肽。它不仅具有和心钠素一样的利尿、舒张血管、抑制肾素一血管紧张素系统的作用 ,还具有抑制心肌Ｎａ -Ｋ ＡＴＰ酶的作用 ,在调节机体血压和高血压发病中有重要意义。我们最近的研究发现 ,自发性高血压大鼠 (ｓｐｏｎｔａｕｅｏｕｓｌｙｈｙｐｅｒｔｅｎｓｉｖｅｒａｔ,ＳＨＲ)循环血液内的ＫＰ水平显著高于正常对照组Ｗｉｓｔａｒ Ｋｙｏｔｏ大鼠 (Ｗ…     

Renal effects of atrial natriuretic factor in the rats of different ages

Renal effects of an atrial natriuretic factor preparation were compared in 15, 28 and 66-day-old rats. This factor, prepared from atrial tissue of adult rats, was more effective in 28 and 66-day-old rats than in 15-day-old rats. There was a 6 fold increase of sodium excretion in 15-day-old rats and a 60 fold increase in 28-day-old rats. There was also a 15 fold increase in renal sodium excretion in 66-day-old rats receiving a higher dose (0.1 ml/animal). As indicated by the sodium potassium ratio, the increase in renal excretion of sodium was distinctly more pronounced than the increase in renal potassium excretion. In 15, 28 and 60-day-old rats, the increase of urine volume was 2 fold, 4 fold and 5 fold, respectively. The increase of fractional sodium excretion (FE) in rats receiving an atrial factor preparation was distinctly more pronounced than the increase of GFR. In all experiments, the preparation from ventricular tissue of the same animals was ineffective in producing natriuresis or diuresis.     

血管钠肽、 C型钠尿肽和心房钠尿肽舒血管作用的对比

本实验采用离体血管灌流方法,观察和比较血管钠肽（ＶＮＰ）,Ｃ型钠尿肽（ＣＮＰ）和心房钠尿肽（ＡＮＰ）对大鼠肺动脉,腹主动脉和腹腔静脉的舒张作用。．结果表明,ＶＮＰ,ＣＮＰ和ＡＮＰ对离体大鼠的保留内皮与去内皮的肺动脉,腹主动脉和腹腔静脉均有浓度依赖性舒张作用。     

Attenuated diuretic and natriuretic effects of atrial natriuretic peptide in rats with heart failure

Plasma levels of atrial natriuretic peptide (ANP) and renal responses to ANP were examined in rats with chronic cardiac failure produced by coronary artery ligation and in sham-operated controls. Plasma ANP levels were elevated in the rats with severe cardiac failure as compared with the controls (P less than 0.001). ANP injections at the doses of 1, 5, 25 and 50 micrograms/kg increased water and sodium excretion significantly at all but the lowest dose in the controls; only the two largest doses caused clear diuresis and natriuresis in the heart failure group. The diuretic and natriuretic effects of ANP were significantly weaker at the doses of 5 and 25 micrograms/kg in the rats with heart failure as compared with the controls. We conclude, that natriuretic and diuretic effects of ANP are attenuated in this chronic heart failure mode.