Detection of humpback whale (Megaptera novaeangliae) non-song vocalizations around the Vema Seamount, southeast Atlantic Ocean.

Humpback whales are a cosmopolitan, highly vocal species. Investigated here are their vocalizations recorded at the Vema Seamount (31°38'S, 08°20'E) from moored hydrophones in the austral spring of 2019. During the 11-d recording period over 600 non-song calls were detected. Calls were predominantly detected at night over three consecutive days. The most common calls were low, frequency-modulated sounds (whups). An impulsive sound (gunshot) previously unknown in humpback whales was also detected. The location and timing of the calls suggests that humpback whales may be using the Vema Seamount as a temporary stop on their migration to their polar feeding grounds.

Physiological role of silent receptors of atrial natriuretic factor.

A ring-deleted analog of atrial natriuretic factor--des[Gln18, Ser19, Gly20, Leu21, Gly22] ANF4-23-NH2 (C-ANF4-23)--binds with high affinity to approximately 99% of ANF receptors in the isolated perfused rat kidney. In this preparation, C-ANF4-23 is devoid of detectable renal effects and does not antagonize any of the known renal hemodynamic and natriuretic actions of biologically active ANF1-28. In contrast, both C-ANF4-23 and ANF1-28 increase sodium excretion and decrease blood pressure in intact anesthetized rats. This apparent contradiction is resolved by the finding that the ring-deleted analog markedly increases plasma levels of endogenous immunoreactive ANF in the rat. The results show that the majority of the renal receptors of ANF are biologically silent. This new class of receptors may serve as specific peripheral storage-clearance binding sites, acting as a hormonal buffer system to modulate plasma levels of ANF.

Albumin absorption and catabolism by isolated perfused proximal convoluted tubules of the rabbit.

Overall characteristics and kinetics of tubular absorption of albumin (Alb) were studied in isolated perfused proximal convoluted tubules of the rabbit. The fate of absorbed Alb was determined in tubules perfused with low [Alb]. Alb was labeled with tritium by reductive methylation ( [3H3C]Alb). At [Alb] = 0.03 mg/ml, approximately 80% of the absorbed [3H3C]Alb was released to the peritubular bathing solution as catabolic products. Transcellular transport of intact [3H3C]Alb was negligible. Iodoacetate (IAA, 4 mM) inhibited albumin absorption (JAlb) by greater than 95% and fluid reabsorption (JV) by 55%. At [Alb] = 0.1 mg/ml the absorption rate of a derivatized cationic Alb (pI = 8.4) was fivefold greater (P less than 0.01) than that of anionic Alb. Higher cationic [Alb] had deleterious effects on tubular functions. Overall Alb absorption was of high capacity and low affinity (JmaxAlb = 3.7 ng/min per mm tubule length, apparent Michaelis constant (Km) = 1.2 mg/ml). A low capacity system that saturates at near physiological loads was also detected (JmaxAlb = 0.064 ng/min per mm, apparent Km = 0.031 mg/ml). High [Alb] did not alter the rate of endocytic vesicle formation as determined by the tubular uptake of [14C]inulin. Results show that Alb absorption is a saturable process that is inhibited by high IAA concentrations and is affected by the charge of the protein. Absorbed Alb is hydrolyzed by tubular cells and catabolic products are readily released to the peritubular side. The dual kinetics of Alb absorption may be due to a combination of adsorptive endocytosis (low capacity system) and fluid endocytosis of albumin aggregates (high capacity system). Results indicate that albuminuria occurs much before albumin absorption is saturated. The kinetic characteristics of the process of tubular absorption of albumin helps to explain the concomitance of albuminuria, increased renal catabolic rates of albumin, and renal cell deposition of protein absorption droplets in severe glomerular proteinurias.

Atrial natriuretic factor inhibits angiotensin-, norepinephrine-, and potassium-induced vascular contractility.

We have previously shown that the natriuretic effect of rat atrial extract (AE) may be due, perhaps entirely, to its powerful renal hemodynamic actions. The present study was undertaken to test the hypothesis that mammalian atria contain a substance that behaves as a functional antagonist of endogenous vasoconstrictors, by examining the direct effects of AE and extensively purified atrial "natriuretic" factor on the contractile response of rabbit aortic rings to angiotensin II (AII), norepinephrine (NE), and K+-induced depolarization. Dose-response curves to AII and NE (i.e., change in tension vs log hormone concentration) were determined in the absence or presence of boiled AE or ventricular extracts (VE). Increasing concentrations of boiled AE caused a progressive right-ward shift of the AII and NE dose-response curves, whereas VE was without effect. A similar inhibitory effect was produced after extensive purification of atrial natriuretic factor by gel filtration and reversed-phase high performance liquid chromatography (HPLC). It appeared that this factor antagonized AII-induced contractility to a greater degree than that of NE. Moreover, the partially purified factor also inhibited the contraction induced by depolarization with 15 mM KCl in a concentration-dependent manner. These studies show that a substance present in the atria, but not ventricles, blocks both hormone- (receptor) and depolarization- (nonreceptor) induced vasoconstriction in aortic rings. Moreover, this antagonism is retained following extensive purification of an atrial factor that induces natriuresis in the intact rat and isolated rat kidney, suggesting that both the vasoactive and natriuretic properties of AE may reside in a single substance.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular effects of atrial natriuretic factor in anesthetized and conscious dogs.

Atrial natriuretic factor lowers blood pressure in normotensive and hypertensive animal models. The present study examined the mechanism of the blood pressure-lowering effect in 10 normotensive dogs. Four awake dogs previously instrumented with electromagnetic flow probes for measurement of cardiac output and catheters for systemic hemodynamic and cardiac dynamic measurements were studied. After a 30-minute control period, a 3 micrograms/kg bolus followed by 0.3 micrograms/min/kg of a 24-residue synthetic atrial natriuretic factor was infused for 30 minutes, followed by a 1-hour recovery period. Mean arterial pressure fell significantly during infusion (control, 125 +/- 4; infusion, 108 +/- 5; recovery, 125 +/- 9 mm Hg; p less than 0.05) and was accompanied by a slight but significant bradycardia (control, 144 +/- 7; infusion, 134 +/- 5; recovery, 145 +/- 7 beats/min; p less than 0.05). Significant reductions in cardiac output (control, 2.66 +/- 0.60; infusion, 2.18 +/- 0.60; recovery, 2.74 +/- 0.60 L/min; p less than 0.05), stroke volume (control, 18.4 +/- 3.9; infusion, 16.0 +/- 4.2; recovery, 19.0 +/- 3.7 ml/beat; p less than 0.05), and maximum increase in rate of change of left ventricular systolic pressure (control, 2475 +/- 200; infusion, 2088 +/- 216; recovery, 2487 +/- 243 mm Hg/sec; p less than 0.05) were also observed during infusion. No significant changes in total peripheral resistance or central venous pressure were noted, although the latter tended to fall during infusion. A similar pattern was observed in six pentobarbital-anesthetized dogs, except that infusion of atrial natriuretic factor did not induce bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of atrial natriuretic factor on blood pressure, renin, and aldosterone in Goldblatt hypertension.

We previously provided evidence that atrial natriuretic factor (ANF) antagonizes angiotensin II-induced vascular contractility and angiotensin II-stimulated aldosterone production by isolated adrenal cells. To examine the importance of these effects in vivo, synthetic ANF (auriculin A) was administered intravenously (2 micrograms/kg bolus followed by 0.3 microgram/kg/min constant infusion) to conscious, unrestrained two-kidney, one-clip and one-kidney, one-clip rats on normal sodium intake and their sham-operated controls. The one-kidney, one-clip rats also were studied on a sodium-deficient diet. Mean blood pressure, plasma renin activity, and plasma aldosterone levels were measured before and after 60-minute infusion. In saralasin-responsive two-kidney, one-clip rats (n = 10), ANF administration reduced blood pressure (from 187 +/- 11 [SE] to 153 +/- 11 mm Hg; p less than 0.001) and plasma aldosterone levels (from 182 +/- 61 to 125 +/- 60 ng/dl; p less than 0.05), while plasma renin activity increased (from 59 +/- 16 to 82 +/- 20 ng/ml/hr; p less than 0.05). Lesser changes in blood pressure occurred in saralasin-nonresponsive two-kidney, one-clip rats (149 +/- 10 to 143 +/- 8 mm Hg; n = 5), sodium-replete one-kidney, one-clip rats (183 +/- 9 to 170 +/- 11 mm Hg; n = 9), two-kidney sham-operated rats (122 +/- 3 to 115 +/- 4 mm Hg; n = 8), and one-kidney sham-operated rats (117 +/- 3 to 112 +/- 3 mm Hg; n = 7). Control plasma renin and aldosterone levels were not elevated in these latter groups and did not change significantly with ANF administration. In sodium-depleted one-kidney, one-clip rats, which became saralasin responsive, ANF administration significantly reduced blood pressure (from 184 +/- 11 to 156 +/- 12 mm Hg; n = 8), plasma aldosterone levels (from 286 +/- 41 to 179 +/- 36 ng/dl), and plasma renin activity (from 69 +/- 19 to 44 +/- 13 ng/ml/hr).(ABSTRACT TRUNCATED AT 250 WORDS)

Endocytosis and lysosomal hydrolysis of proteins in proximal tubules.

The techniques and basic protocols described above can be readily reproduced by investigators with experience in perfusion of isolated nephron segments. They can be modified and adapted by the investigator to address specific issues. In particular, isolated perfused nephron segments have also been successfully used for elucidation of biochemical and morphological aspects of endocytosis and lysosomal hydrolysis of macromolecules, proteins, and polypeptides. The reader is directed to the references cited under Methodological Approaches in this chapter for a description of these techniques. Although studies on the endocytic uptake and metabolism of proteins and polypeptides using isolated perfused nephron segments have made significant inroads in our understanding of these fascinating and important biological processes, much remains to be learned. Hopefully, future uses of the technique will further advance our knowledge in this field.

Renal handling of low molecular weight proteins.

The renal filtration, absorption and final disposal of lysozyme (lysozyme--mol wt 14,000), insulin and growth hormone were studied to gain a better quantitative understanding of the fundamental variables involved in the renal handling of low molecular weight proteins. The glomerular barrier offers little hindrance to the filtration of lysozyme, the glomerular sieving coefficient being 0.8 plus or minus 0.1 (SD). The intrarenal route by which injected lysozyme accumulates in the kidney is via filtration and subsequent absorption (uptake) by renal tubular cells. Uptake or adsorption from the peritubular side is negligible compared to luminal uptake. Renal clearance and renal titration experiments in the intact dog and in the isolated perfused rat kidney showed that the lysozyme absorption process can be best characterized as high capacity, low affinity transport system which is directly or indirectly dependent on energy input. The final disposal of absorbed 125I-lysozyme, 125I-insulin and 125I-growth hormone was studied in the isolated perfused rat kidney by measuring the radioactivity by gel chromatography. The rate of release of radioactivity as well as its nature was dependent on the molecular species of the absorbed protein. The rate of release was higher for 125I-insulin and 125I-growth hormone and lower for 125I-lysozyme. Lysozyme absorbed from the luminal side was released to the perfusate both as intact protein molecules and as catabolic products, whereas absorbed 125I-insulin was almost entirely released to the perfusate as catabolic products. It is concluded that low molecular weight proteins are extensively filtered by the kidney, absorbed from the luminal side by renal tubular cells and released back to the circulation either as intact molecules or as catabolic products (amino acids and polypeptides). This process contributes in an important way to the plasma turn-over of low molecular weight proteins including peptides and proteins hormones.

Effects of auriculin (atrial natriuretic factor) on blood pressure, renal function, and the renin-aldosterone system in dogs.

Auriculin is a potent vasoactive and natriuretic peptide that was recently isolated and purified from rat atrial tissue. Since this peptide could be of great importance for renal, cardiovascular, and volume homeostasis, its functional properties have been characterized in dogs. The effects of synthetic auriculin on renal function, mean blood pressure, plasma renin activity, renin secretory rate, and plasma aldosterone levels were determined. Auriculin was administered intravenously as a prime (1.0 microgram/kg body weight) and constant infusion (0.1 microgram per minute/kg body weight for one hour) to five anesthetized dogs. In addition, two conscious dogs were used to verify some of the results obtained in anesthetized dogs. Auriculin decreased mean blood pressure from 134 +/- 5 to 122 +/- 4 mm Hg (p less than 0.05, paired t test) and increased glomerular filtration rate (25.5 +/- 2.7 to 32.4 +/- 4.1 ml per minute per kidney, p less than 0.05), diuresis (0.21 +/- 0.03 to 1.06 +/- 0.14 ml per minute per kidney, p less than 0.05), natriuresis (38 +/- 0.6 to 187 +/- 35 mueq per minute per kidney, p less than 0.05), and kaliuresis (14.8 +/- 1.6 to 35.7 +/- 6.3 mueq per minute per kidney, p less than 0.05). These effects were sustained throughout the infusion of auriculin and were entirely reversible. Renal plasma flow increased transiently for one to two minutes, and then returned to or below control levels. Urine osmolality decreased by 40 percent (p less than 0.05) whereas free water clearance remained unchanged (p less than 0.05). Auriculin reversibly decreased plasma renin activity (11.6 +/- 2.3 to 3.6 +/- 1.2 ng/ml per hour, p less than 0.05), renin secretory rate (895 +/- 313 to 255 +/- 28 ng per hour per minute, p less than 0.05), and plasma aldosterone levels (8.4 +/- 1.6 to 3.6 +/- 0.7 ng/dl, p less than 0.05), whereas plasma cortisol levels remained unchanged. These results demonstrate that auriculin has a unique combination of functional properties, increasing glomerular filtration rate, diuresis, and natriuresis, without a sustained increase in total renal blood flow, and lowering blood pressure, plasma renin levels, renin secretory rate, and plasma aldosterone levels. These properties suggest an important potential role for atrial natriuretic peptides in the regulation of renal function, extracellular volume, and blood pressure.

Effects of atrial natriuretic factor on the kidney and the renin-angiotensin-aldosterone system.

ANF is a peptide hormone with peripheral and central effects on several physiologic control systems, which suggests broad involvement in the regulation of intravascular volume and cardiovascular homeostasis. ANF acts directly on the kidney to modulate renal vascular resistance, increase glomerular filtration rate, and decrease inner medullary hypertonicity. These hemodynamic effects act in concert to promote marked natriuresis and diuresis and to inhibit renin secretion by the kidney; the potential role of direct effects on tubular transport and on the juxtaglomerular cells remains to be clarified. ANF also inhibits steroidogenesis, most prominently affecting agonist-induced aldosterone biosynthesis by the adrenal cortex. ANF exerts a smooth muscle relaxant effect on isolated vessels constricted with various hormonal agonists. ANF causes especially pronounced antagonism of the adrenal and vascular actions of angiotensin II and antagonizes the latter peptide's central nervous system effects. Although complex systemic hemodynamic mechanisms are involved, ANF-induced vasorelaxation may contribute to its depressor action, particularly in states characterized by angiotensin II-induced vasoconstriction. Distention of the atria is a major stimulus to ANF release and evokes many responses that are mimicked by ANF infusion. Although ANF is not the sole or even dominant mediator of the responses to atrial distention, available data suggest that it plays a role in the renal and hormonal responses to intravascular volume expansion. Definitive assessment of its physiologic and pathophysiologic significance must await development of specific antagonists, but further studies on the mechanisms of action of ANF at the molecular, cellular, and systemic levels are likely to contribute significantly to our understanding of the complex process of volume regulation and cardiovascular homeostasis.

Conversion of T-kinin to bradykinin by the rat kidney.

Isolated rat kidneys were perfused with T-kinin (TK, Ile-Ser-BK) and bradykinin (BK). HPLC analysis of perfusate samples taken at 2-10 min during the TK perfusion (0.5 nmol/mL initial concentration) showed two peptide peaks, the first one eluting at 14.42 min, the same retention time for standard BK, and the second at 16.20 min, corresponding to that of TK. When BK (0.5 nmol/mL) was perfused, only its corresponding peak was obtained although total BK recovery was reduced quickly, as expected. Using both HPLC analysis and a kinin bioassay on the isolated guinea pig ileum, it was found that 12% of the added TK was converted to BK during the first perfusion cycle (2 min). While the BK recovered (12-14% from the initial TK concentration) was maintained at a similar proportion between the 2nd and the 10th min of perfusion, the rate of TK disappearance, as well as its full recovery from the perfusate, indicated further fragmentation of peptides during kinin perfusion. In the presence of 5 microM DL-mercaptomethyl-3-guanidino-ethylthiopropanoic acid (Mergetpa), an inhibitor of plasma carboxypeptidase N (EC 3.4.17.3), the rate of conversion of TK to BK was not affected. On the other hand, the kinase II inhibitor bradykinin potentiating peptide 9a (BPP9a) increased both the proportion of TK converted to BK and the disappearance rate of TK from the perfusate. In the presence of BPP9a, the rate of BK production increased from 1.5 +/- 0.2 to 7.6 +/- 0.9 nmol/min. Furthermore, the recovery of BK was reduced during the first 2 min of perfusion to 7.6% and the conversion rate to 0.9 nmol/min when TK was perfused into the kidney in the presence of 10 microM bestatin, a known inhibitor of aminopeptidases. These data indicate that in the kidney TK is converted to BK, probably by aminopeptidase M, thus suggesting that BK is, in fact, an additional and functional kinin, inducing physiological and/or pathophysiological effects in the rat kidney in which TK is the main kinin released.

DuP 753 is a potent nonpeptide antagonist of angiotensin II receptors in isolated perfused rat kidney and cultured renal cells.

In the present study we investigated the antagonist action of DuP 753 (2-n-butyl-4-chloro-5-hydroxy-methyl-1-[2'-(1H-tetrazol-5-yl)biphe nyl-4-yl) methyl]imidazole, potassium salt) on angiotensin II (AII) binding and vascular effects in the isolated perfused rat kidney. In addition, we determined binding of DuP 753 in cultured glomerular mesangial cells and renomedullary interstitial cells. In the isolated kidney, DuP 753 fully displaced AII from its specific binding sites with high affinity (IC50 = 200 nmol/L) and antagonized the vasoconstrictive effect of AII in a dose-related manner with an ED50 of 170 nmol/L. These effects of DuP 753 were qualitatively similar to those of saralasin and the antagonist effect of DuP 753 on AII-induced renal vasoconstriction was fully overcome by excess AII. DuP 753 had no effect on its own on renal vascular resistance. In cultured glomerular mesangial cells and renomedullary interstitial cells, DuP 753 fully inhibited the specific binding of [125I]-Sar-AII at 1 mumol/L with IC50s of 6.7 and 11 nmol/L for glomerular mesangial cells and renomedullary interstitial cells, respectively. The present results demonstrate that a novel imidazole derivative, DuP 753, is a powerful non-peptide antagonist of angiotensin II receptors in isolated perfused rat kidney and in cultured glomerular mesangial and renomedullary interstitial cells.

Renal vasoconstrictive effect of kinins mediated by B1-kinin receptors.

The nature of the renal vascular actions of kinins, their dependence on prostaglandins and B1-kinin receptor responses were studied in functioning isolated perfused rat kidneys (IK). Lysylbradykinin (LBK), 0.28 and 0.7 microM, transiently decreased and then markedly increased the renal vascular resistance (RVR) in a sustained manner. Bradykinin (BK) at the same doses also had a transient vasorelaxant but not a sustained vasoconstrictive effect. The inactivation of LBK and BK by the IK did not account for the transient nature of their vasorelaxant effect. Indomethacin (5 microM) markedly blunted LBK-induced decrease but not increase in RVR. The B1-kinin receptor agonist desArg9-BK (0.4-1.0 microM) did not decrease RVR but, as LBK, markedly increased RVR in a dose-related manner. The B1-kinin receptor antagonist [Leu8]desArg9-BK had no effect on its own but inhibited the desArg9-BK-induced vasoconstriction in a stoichiometric manner. This antagonist at 4.0 microM also completely abolished the vasoconstrictive effect of 0.7 microM LBK, whereas it potentiated and prolonged its vasorelaxant effect. The results demonstrate that kinins, particularly LBK, have bimodal effects on the renal vascular resistance of the isolated perfused rat kidney. The vasorelaxant effect is at least partly mediated by prostaglandins whereas the vasoconstrictive effect of LBK and/or its renal metabolites has the typical character of a B1-kinin receptor response. It is postulated that B1-kinin receptor responses may be of importance in the generation and/or maintenance of renal vasoconstriction in disease states which lead to renal failure.

Role of increased glomerular filtration rate in atrial natriuretic factor-induced natriuresis in the rat.

One of the major renal hemodynamic actions of atrial natriuretic factor (ANF) is to increase glomerular filtration rate (GFR). To assess the role of this effect on ANF-induced natriuresis (UNaV), diuresis (V) and kaliuresis (UKV) we performed late clamp experiments in six rats. After control periods (C), synthetic ANF (auriculin A) was infused i.v. (2 micrograms X min-1/kg body wt) throughout the experiment (150 min). After pre-clamp periods, the perfusion pressure of the left kidney (LK) was reduced to 75-80 mmHg. The right kidney (RK) served as a time control. In LK, before the late clamp, ANF increased (p less than 0.01) GFR from 1.5 +/- 0.1 to 1.8 +/- 0.1 ml/min, V from 17 +/- 5 to 53 +/- 5 microliters/min, and UNaV from 2.1 +/- 0.6 to 10.0 +/- 0.9 microEq/min. Almost identical increases occurred in the RK. The late clamp returned all parameters in LK to C values (p greater than 0.05): GFR to 1.4 +/- 0.1 ml/min, V to 6.3 +/- 1.2 microliter/min, and UNaV to 1.0 +/- 0.3 microEq/min. The late clamp also reversed the ANF-induced increase in UKV. In the RK, GFR (1.8 +/- 0.1 ml/min), V (38 +/- 4 microliter/min) and UNaV (7.8 +/- 0.8 microEq/min) remained elevated (p less than 0.01 vs. C) to the end of the experiment. These data demonstrate that upon return of GFR to control levels, the ANF-induced diuresis, natriuresis and kaliuresis is abolished. The results support our previous view that the increase in GFR together with a decrease in inner-medullary hypertonicity account wholly or in great part for the natriuretic action of ANF.

Atrial natriuretic factor increases hematocrit and decreases plasma volume in nephrectomized rats.

To test the hypothesis that ANF increases the efflux of fluid from capillaries we determined the effect of synthetic (1-28) ANF on hematocrit (Hct) and plasma volume (PV) in 24 hr bilaterally nephrectomized rats. Results were compared with those obtained in bilaterally nephrectomized rats receiving saline alone (S) or an infusion of sodium nitroprusside (NP) to produce a similar blood pressure lowering effect as ANF. PV was determined by the volume of distribution of RISA 10 minutes after its i.v. administration. After control periods (C) rats were infused for 40 minutes with saline alone (group A, n = 8), (1-28)ANF, 0.3 micrograms X min-1/kg body wt (group B, n = 9), 1.0 microgram X min-1/kg body wt (group C, n = 8) and NP, 1.0 to 2.0 micrograms X min-1/kg body wt (group D, n = 8). Recovery periods (R) were performed 45 minutes after the experimental periods (E). During E periods, mean arterial blood pressure did not change in group A and fell significantly (p less than 0.01) in the other groups. Group B: C = 89 +/- 4; E = 82 +/- 4 mmHg. Group C: C = 106 +/- 7; E = 92 +/- 7 mmHg. Group D: C = 104 +/- 5; E = 90 +/- 5 mmHg. Neither saline or NP changed Hct, whereas, ANF significantly (p less than 0.01) increased this parameter (Group B: C = 43.4 +/- 0.7; E = 46.3 +/- 0.6% and Group C: C = 44.5 +/- 1.2; E = 47.4 +/- 1.2%). ANF significantly decreased PV (3.86 +/- 0.14 ml/100 gm body wt) as compared to S (4.51 +/- 0.22 ml/100 gm body wt; p less than 0.05) or NP (4.69 +/- 0.11 ml/100 gm body wt; p less than 0.01). The average decrease in PV of 14% corresponded to the average increase in Hct of 7%. Results demonstrate that ANF increases the efflux of fluid from capillaries. This effect explains, at least in part, the ANF-induced decrease in cardiac output and blood pressure in normotensive animals and may play an important role in the homeostatic regulation of plasma volume.

High salt intake increases the vasorelaxant effect of ANF on the isolated perfused rat kidney.

1. The objective of the present study was to determine whether chronic salt load or depletion leads to adaptive changes in kinetics of atrial natriuretic factor (ANF) binding and/or responsiveness to ANF. We measured the equilibrium binding to and the steady-state dose-response effects of ANF1-28 on isolated kidneys from rats kept on a high (H) or low (L) salt diet for 15 days. 2. Twenty-four hour sodium excretion was 5.90 +/- 0.46 mEq for H vs 0.06 +/- 0.01 mEq for L (P less than 0.01). Plasma levels of immunoreactive ANF of H (42.2 +/- 3.9 pg/ml) were not significantly different from those for L (35.2 +/- 5.3 pg/ml). 3. There was no significant differences in distribution, apparent density or affinity of ANF specific binding sites determined in non-filtering isolated kidneys from rats kept on the H or L salt diet. 4. Dose-response curves for the hemodynamic and excretory effects of ANF1-28 in filtering isolated kidneys from rats kept on the H salt diet were not different from those of rats kept on the L salt diet. In contrast, the vasorelaxant response to ANF1-28 in isolated kidneys preconstricted by adding serum from 24-h nephrectomized rats to the perfusate (generation of angiotensin II) was significantly more pronounced in kidneys front rats chronically adapted to the high-salt diet. 5. This effect of ANF may contribute to the increased renal plasma flow and glomerular filtration rate occurring under conditions of chronic salt loading in intact animals.

Effects of kinins on the isolated perfused rat kidney and evidence for the presence of renal B1 receptors.

The kinins, particularly lysyl-bradykinin (LBK), have a bimodal effect on the vasculature of isolated rat kidney. The vasorelaxant but not the vasoconstrictor effect of LBK seems to be mediated by prostaglandins. The vasoconstrictor action of LBK can be blocked by (L-Leu)8-des-Arg9-BK indicating that the rat kidney vasculature has B1 kinin-receptor which mediates the effects of kinins and/or their C-terminal metabolites.

[Structure and biological action of the atrial natriuretic factor (auriculin)]. / Struktura i biologicheskoe deistvie predserdnogo natriiureticheskogo faktora (aurikulina).

The studies described in this report emphasize the potential importance of atrial natriuretic factor in affecting systemic and renal hemodynamics, sodium excretion and components of the renin-angiotensin-aldosterone system. It should be emphasized, however, that at present there is no direct and unequivocal evidence that ANF is secreted into the blood. Until this is done and until the factors that regulate its secretion have been established, its potential physiological role must remain speculative.

Effect of atrial natriuretic factor on renin secretion, plasma renin and aldosterone in dogs with acute unilateral renal artery constriction.

Atrial natriuretic factor (ANF) decreases renin secretion rate (RSR), plasma renin activity (PRA) and plasma aldosterone (PA) in normal dogs. To clarify further the mechanisms responsible for these effects, the left renal artery was constricted in seven anaesthetized dogs prior to ANF administration. Constriction of the left renal artery decreased (P < 0.05) ipsilateral mean renal perfusion pressure (MRPP, 29 +/- 7%), renal plasma flow (RPF, 42 +/- 11%) and glomerular filtration rate (GFR) and filtered sodium load (FLNa, 21 +/- 8.8%). Ipsilateral RSR and peripheral PRA tended to increase, although not significantly. Atrial natriuretic factor infusion did not alter GFR in the clamped kidney and failed to decrease RSR or PRA. Despite this, PA levels decreased significantly (7.8 +/- 2.4 to 5.6 +/- 1.8 ng%). These results suggest that ANF-induced inhibition of renin secretion is largely consequent on its renal haemodynamic actions and that suppression of aldosterone by ANF in vivo is due, in part, to direct effects on the adrenal cortex.