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R H Freeman

Publications and source records attributed to R H Freeman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Prouroguanylin and proguanylin: purification from colon, structure, and modulation of bioactivity by proteases.

Uroguanylin and guanylin are peptides isolated from urine and intestinal mucosa, which regulate cyclic GMP production in enterocytes by activating an apical membrane, receptor-guanylate cyclase. This study extended our previous findings, which showed that colonic mucosa of opossums contained uroguanylin and guanylin peptides, by purifying prouroguanylin and proguanylin from this tissue. Prouroguanylin and proguanylin coeluted from Sephadex G-75 gelfiltration columns with a similar molecular size between 6 and 12 kDa. Mass spectrometry indicated that proguanylin (approximately 8.7 kDa) had a 10% lower molecular mass than prouroguanylin (approximately 9.7 kDa). Isoelectric focusing separated prouroguanylin (pI approximately 4.5) from proguanylin (pI approximately 7.5). N-terminal sequence analysis of reverse phrase-HPLC purified prohormones revealed 13 amino acids in opossum proguanylin that shared 77-85% identity with human and rat proguanylin, but only 23% identity with opossum prouroguanylin. The N-terminal 19 residues obtained for opossum prouroguanylin shared 32-42% identity with rat and human proguanylin. Prouroguanylin and proguanylin were both inactive and required pretreatment with proteases to elicit cyclic GMP responses in T84 cells. V8 protease treatment of proguanylin liberated a bioactive, 16-amino acid form of guanylin. Chymotrypsin treatment activated prouroguanylin, but inactivated the bioactive peptide domain within proguanylin. In summary, colonic mucosa contains the bioactive peptide and inactive prohormone forms of uroguanylin and guanylin. Thus, after proteolytic processing of prouroguanylin and proguanylin, bioactive uroguanylin and guanylin could both function to regulate guanylate cyclase activity by autocrine and/or paracrine actions on enterocytes. Also, these peptide hormones are implicated in an intestinal-renal axis for the endocrine regulation of salt and water homeostasis.

Amino Acid Sequence↗
PubMed1995

Atrial natriuretic peptide fragments in dogs with experimental heart failure.

1. This study in the canine arteriovenous (AV) fistula model of high-output heart failure (HOHF) evaluated the chronic temporal changes in plasma ANF and pro ANF 31-67 and their relationship to body-fluid balance and the renin-aldosterone axis. In addition, the haemodynamic, hormonal and renal excretory effects of synthetic pro ANF 31-67 infusions were examined in normal and AV fistula dogs with compensated HOHF. 2. Following the construction of the AV fistula, the dogs exhibited chronic parallel elevations in right atrial pressure and the plasma concentrations of ANF and pro ANF 31-67. The gradual increases in the two peptides were associated with a gradual decrease in plasma renin activity and the re-establishment of sodium balance. 3. In normal and compensated AV fistula dogs, synthetic pro ANF 31-67 produced similar significant reductions in arterial blood pressure, right atrial pressure and elevations in urinary sodium excretion. These effects were not associated with increases in plasma or urinary cyclic GMP (cGMP). 4. These results suggest that the elevation in the endogenous circulating levels of pro ANF 31-67 in the AV fistula dogs may represent one chronic adaptive mechanism to achieve body fluid homeostasis. Furthermore, via potentially different mechanisms of action, ANF and pro ANF 31-67 may coordinate and contribute to the regulation of haemodynamic and renal function during physiological and pathophysiological situations.

Animals↗
PubMed1995

L-arginine analogues inhibit aldosterone secretion in rats.

L-Arginine analogues, e.g., NG-nitro-L-arginine methyl ester (L-NAME), increase arterial pressure and suppress renin release in the rat. On the basis of these observations, it was hypothesized that L-arginine analogues also would attenuate aldosterone secretion. This hypothesis was tested in anesthetized rats treated with L-NAME or NG-nitro-L-arginine (L-NNA, 185 mumol/kg ip). The aldosterone secretion rate, plasma renin activity, and adrenal blood flow were attenuated in rats treated with L-NAME and L-NNA compared with control animals. Similar experiments were performed in anephric rats to examine the effects of L-NAME on aldosterone secretion independent of the circulating reninangiotensin system. The administration of L-NAME reduced adrenal blood flow but failed to reduce aldosterone secretion in these anephric rats. Bilateral nephrectomy reduced plasma renin activity essentially to undetectable levels in these animals. In a third series of experiments, two groups of anephric rats were infused with angiotensin II (3 micrograms/kg body wt iv) to provide a stimulus for aldosterone secretion. Aldosterone secretion and adrenal blood flow were markedly reduced in angiotensin II-infused rats pretreated with L-NAME compared with the control anephric animals infused with angiotensin II. Overall these results suggest that L-arginine analogues attenuate aldosterone secretion by inhibiting the adrenal steroidogenic effects of endogenous or exogenous angiotensin II and/or by reducing plasma levels of renin/angiotensin.

Aldosterone↗
PubMed1995

Distribution of Escherichia coli heat-stable enterotoxin/guanylin/uroguanylin receptors in the avian intestinal tract.

Pathogenic strains of enteric bacteria secrete small heat-stable toxins (STs) that activate membrane guanylyl cyclase receptors found in the intestine. The intestinal peptide agonists, guanylin and uroguanylin, are structurally related to STs. Receptors for 125I-ST were found throughout the entire length of the intestinal tract of all the birds examined. These receptors were restricted to intestinal epithelial cells covering villi and forming intestinal glands and were not observed in other strata of the gut wall. The most intense labeling of receptors by 125I-ST occurred in the region of the microvillus border of individual enterocytes. There appeared to be a decrease in receptor density distally along the length of the small intestine, although labeling of receptors by 125I-ST was observed throughout the small intestine and colon. Cellular cGMP accumulation responses to Escherichia coli ST and rat guanylin in the domestic turkey and duck were greater in the proximal small intestine compared to the distal small intestine or colon. Brush border membranes (BBM) isolated from the mucosa of proximal small intestine of turkeys exhibited agonist-stimulated guanylyl cyclase activity. The rank order potency for enzyme activation was E. coli ST > uroguanylin > guanylin. Competitive radioligand binding assays using 125I-ST and turkey intestine BBM revealed a similar rank order affinity for the receptors that was exemplified by the Kd values of ST 2.5 nM, uroguanylin 80 nM and guanylin 2.6 microM. It may be concluded that functional receptors for the endogenous peptides, guanylin and uroguanylin, occur in the apical membranes of enterocytes throughout the avian intestine. The receptor-guanylyl cyclase(s) of proximal small intestine were preferentially activated by uroguanylin relative to guanylin, but both endogenous peptides were less potent than their molecular mimic, E. coli ST.

Amino Acid Sequence↗
PubMed1994

Effects of renal denervation on postprandial sodium excretion in experimental heart failure.

The hormonal, hemodynamic and renal excretory changes after an oral load of sodium were examined in renal-denervated dogs with an arteriovenous (AV) fistula and the syndrome of compensated high-output heart failure. After ingestion of a meal containing 125 meq of sodium, the total postprandial urinary sodium excretion and fractional sodium excretion were approximately twofold higher in the renal-denervated AV fistula dogs, compared with a control group with intact renal nerves (P < 0.05). The postprandial elevations in right atrial pressure, plasma atrial natriuretic factor, and filtered load of sodium were similar in the two groups (P > 0.05). Mean arterial pressure and plasma renin activity remained unchanged from baseline in the two subsets of animals (P > 0.05). In the renal-denervated AV fistula dogs, ingestion of a low-salt meal containing 2-3 meq of sodium produced elevations in creatinine clearance and filtered load of sodium of similar magnitude to the high-salt meal. However, the increases in sodium excretion and plasma atrial natriuretic factor were modest and inconsistent. These results demonstrate that the renal nerves play an important modulatory role for postprandial sodium metabolism after a high-salt meal in experimental compensated high-output heart failure. It is suggested that the renal nerves attenuate the expression of postprandial natriuretic mechanisms via a direct tubular mechanism of action.

Animals↗
PubMed1994

Renin release in rats during blockade of nitric oxide synthesis.

The influence of renal perfusion pressure on renin release was examined in rats administered the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Compared with the control plasma renin of 6.0 +/- 0.7 ng angiotensin I (ANG I).ml-1.h-1, plasma renin activity was suppressed (1.8 +/- 0.2 ng ANG I.ml-1.h-1, P < 0.05) in L-NAME-treated animals in which the renal perfusion pressure was permitted to increase and reached 141 +/- 8 mmHg. Plasma renin activity also was suppressed (2.5 +/- 0.4 ng ANG I.ml-1.h-1, P < 0.05) in a second L-NAME-treated group in which the renal perfusion pressure was controlled to a level of 105 +/- 5 mmHg via tightening of a suprarenal aortic snare. Plasma renin activity was increased (12.0 +/- 1.4 ng ANG I.ml-1.h-1, P < 0.05) in a third L-NAME-treated group in which renal perfusion pressure was reduced to 59 +/- 1 mmHg. Overall, these findings suggest that the intrarenal pressure-sensing mechanism for renin release does not stringently require nitric oxide synthesis. In a second experimental series, bilaterally renal-denervated rats were administered L-NAME, and again plasma renin activity was suppressed significantly whether renal perfusion pressure was permitted to increase or was controlled. Thus L-NAME also suppressed plasma renin activity independently of reflex reductions in renal neuroadrenergic activity even when renal perfusion pressure was controlled. Infusions of sodium nitroprusside completely inhibited L-NAME-induced suppression of plasma renin activity in these renal-denervated rats. Nitric oxide may function as a paracrine stimulatory mechanism for the local regulation of renin release.

Animals↗
PubMed1994

Induction of differentiation and growth arrest associated with nascent (nonoligosomal) DNA fragmentation and reduced c-myc expression in MCF-7 human breast tumor cells after continuous exposure to a sublethal concentration of doxorubicin.

The effects on DNA integrity of continuous (72-h) exposure of human MCF-7 breast adenocarcinoma cells to 50 nM doxorubicin (a concentration which can be maintained in the plasma by continuous infusion) were characterized by bisbenzimide spectrofluorophotometry, cell flow cytometry, agarose gel electrophoresis, and neutral elution. Spectrofluorophotometry and cell flow cytometry indicated the presence of DNA fragmentation, which was maximal at 24 h. Resolution of these fragments on agarose gels failed to demonstrate "laddered" oligosomal profiles. Neutral elution analysis at 24 h indicated that doxorubicin induced fragmentation of nascent, but not mature, double-stranded DNA. Drug-treated cells exhibited endoreduplication and significant shifts in cell cycle distribution, (i.e., increased G0/G1 and G2/M fractions and a markedly reduced S-phase fraction). These alterations occurred without inhibiting the incorporation of [3H]dThd into cellular DNA; in fact, both the rate and magnitude of [3H]dThd incorporation increased progressively. Doxorubicin also produced a sustained decline in c-myc mRNA levels that paralleled both growth arrest and induction of DNA fragmentation. Ultrastructural examination revealed morphological alterations consistent with the induction of differentiation (e.g., increased lipid content and mitochondrial density, appearance of tight junctions, and secretory ducts) and further suggested the possibility of autocatalysis (e.g., lipofuschin-containing vacuoles). A gradual decline in cell number was observed, with loss of approximately 35% of the cell population after 72 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

Distribution of heat-stable enterotoxin/guanylin receptors in the intestinal tract of man and other mammals.

The human intestinal tract, as well as that of several eutherian and metatherian mammals, was examined for the distribution of heat-stable enterotoxin (ST)/guanylin receptors. These receptors were confined to the intestinal epithelium lining the lumen and forming the intestinal glands throughout the length of both the small intestine and colon of all species examined. In man and most other mammalian species, there appeared to be a decrease in receptor density distally along the longitudinal axis of the small intestine. ST/guanylin receptors were not observed in other strata forming the gut wall. Along the vertical axis of the human small intestine (villus/crypt unit), as well as that of most other mammals, receptor density was greatest in enterocytes located near the base of villi and in those forming the proximal portion of the intestinal glands. ST/guanylin receptors were for the most part confined to the region of the plasmalemma forming the microvillus border. In the colon of man and the other species examined, receptor density was greatest in enterocytes forming the proximal region of the intestinal glands. Receptors were present in the intestinal epithelium lining the lumen of the colon, but generally were fewer in number. The distribution of cellular cGMP accumulation responses to E. coli ST and guanylin in the opossum (Didelphis virginiana) and raccoon (Procyon lotor) revealed that proximal small intestine had greater magnitudes of cGMP responses than did the distal small intestine. Proximal colon had greater cGMP responses than distal colon, which had no significant cGMP responses to either ST or guanylin.

Animals↗
PubMed1993

Uroguanylin: structure and activity of a second endogenous peptide that stimulates intestinal guanylate cyclase.

The intestinal hormone guanylin and bacterial heat-stable enterotoxins (STs) are members of a peptide family that activates intestinal membrane guanylate cyclase. Two different peptides that activate the human intestinal T84 cell guanylate cyclase have been purified from urine and intestinal mucosa of opossums (Didelphis virginiana). The highly acidic peptide, QEDCELCINVACTGC, was named uroguanylin because it was isolated from urine and shares 53% identity with guanylin. A second peptide, SHTCEICAFAACAGC, was purified from urine and intestinal mucosa. This alanine-rich peptide was 47% identical to uroguanylin and 73% identical to human guanylin, suggesting that it may be an opossum homologue of guanylin. Synthetic uroguanylin-(2-15) (i.e., EDCELCINVACTGC) was 10-fold more potent than synthetic rat guanylin, but both peptides were less potent than Escherichia coli ST in the T84 cell cGMP bioassay. Uroguanylin-(2-15) and guanylin inhibited 125I-ST binding to T84 cell receptors in competitive radioligand binding assays. Transepithelial Cl- secretion was stimulated by 1 microM uroguanylin, indicated by an increase in the short circuit current of T84 cells. Thus, uroguanylin is another paracrine hormone in the emerging peptide family that activates intestinal membrane guanylate cyclase. The second peptide may be the opossum form of guanylin, or perhaps, it is still another member of this peptide family. The presence of uroguanylin and guanylin in urine and receptors in proximal tubules suggests that these peptides may also originate from renal tissue and may regulate kidney function.

Amino Acid Sequence↗
PubMed1993

Neurohumoral modulators and sodium balance in experimental heart failure.

The acute and chronic interactions of the renal nerves, atrial natriuretic factor (ANF), and mineralocorticoids for the regulation of sodium balance were examined in dogs with an arteriovenous (AV) fistula and the syndrome of high-output heart failure (HOHF) (n = 6). After the AV fistula and bilateral renal denervation, the animals avidly retained sodium for 5-7 days and then regained sodium balance for the subsequent 3 wk. This compensation was associated with the sustained elevations of plasma ANF and the normalization of plasma renin. Subsequent administration of deoxycorticosterone acetate (DOCA) for 10 days produced consistent sodium retention despite additional elevations in plasma ANF. All of these responses were similar to previous studies in AV fistula dogs with intact renal nerves. In a separate part of the study, the renal actions of acute synthetic ANF infusions were examined in these renal-denervated AV fistula dogs before and after DOCA. In the pre-DOCA experiments, ANF infusions at 15, 30, and 100 ng.kg-1.min-1 produced dose-related increases in urinary sodium excretion and significant elevations in creatinine clearance. In the presence of DOCA, urinary sodium excretion was markedly attenuated during identical ANF infusions. The composite results suggest that mineralocorticoids have an important modulatory role for the regulation of sodium balance in experimental HOHF. However, compared with earlier studies in compensated AV fistula dogs with intact renal nerves, the present studies demonstrate that blockade of efferent renal sympathetic nerve activity can restore the natriuretic expression of acute elevations in circulating ANF.

Animals↗
PubMed1993

Guanylin stimulation of Cl- secretion in human intestinal T84 cells via cyclic guanosine monophosphate.

Intestinal salt and fluid secretion is stimulated by Escherichia coli heat-stable enterotoxins (ST) through activation of a membrane guanylate cyclase found in the intestine. Guanylin is an endogenous intestinal peptide that has structural similarity to the bacterial peptides. Synthetic preparations of guanylin or E. coli ST 5-17 stimulated Cl- secretion in T84 cells cultured on semipermeable membranes as measured by increases in short circuit current (Isc). The guanylin/ST receptors appeared to be on the apical surface of T84 cells, since addition of guanylin to the apical, but not basolateral, reservoir stimulated Isc. Bumetanide added to the basolateral side effectively inhibited the Isc responses of T84 cells to either guanylin or ST 5-17. Guanylin appeared to be about one-tenth as potent as ST in stimulating transepithelial Cl- secretion. Guanylin and E. coli ST 5-17 both caused massive (> 1,000-fold) increases in cGMP levels in T84 cells, but guanylin was less potent than ST. Both peptides fully inhibited the binding of 125I-ST to receptor sites on intact T84 cells. The radioligand binding data obtained with guanylin or ST 5-17 best fit a model predicting two receptors with different affinity for these ligands. The Ki values for guanylin were 19 +/- 5 nM and 1.3 +/- 0.5 microM, whereas the Ki values for ST 5-17 were 78 +/- 38 pM and 4.9 +/- 1.4 nM. We conclude that guanylin stimulated Cl- secretion via the second messenger, cGMP, in T84 human colon cells. At least two guanylin receptors with different affinities for these ligands may exist in the cultured T84 cells. It may be postulated that guanylin is an endogenous hormone that controls intestinal Cl- secretion by a paracrine mechanism via cGMP and that E. coli ST stimulates Cl- secretion by virtue of an opportunistic mechanism through activation of guanylin receptors.

Bacterial Toxins↗
PubMed1992

Sustained hypertension in the rat induced by chronic blockade of nitric oxide production.

It is well established that acute systemic blockage of L-arginine conversion to nitric oxide by NW-nitro-L-arginine methyl ester (L-NAME) and other substituted analogs of L-arginine produces vasoconstriction and elevates the blood pressure. The present study in rats reports that chronic L-NAME injections (185 mumol/L/kg body weight, intraperitoneally; every 12 h) for 4 days produces sustained arterial hypertension which is fully and rapidly reversed by acute administration of excess L-arginine. The magnitude of the hypertension is not different between L-NAME treated rats fed normal or high sodium diets. The results from this simple experimental model suggest that chronic blockade of nitric oxide synthesis results in sustained arterial hypertension that is not enhanced by sodium loading.

Animals↗
PubMed1992

Stimulation of intestinal Cl- transport by heat-stable enterotoxin: activation of cAMP-dependent protein kinase by cGMP.

Heat-stable enterotoxins activate guanylate cyclase, whereas heat-labile enterotoxins stimulate adenylate cyclase. Both classes of toxins cause secretory diarrhea at least in part by stimulating Cl- secretion in the intestine. The mechanism for regulation of Cl- secretion by guanosine 3',5'-cyclic monophosphate (cGMP) was investigated using cultured T84 intestinal cells as a model for intestinal crypt cells. Escherichia coli heat-stable enterotoxin (ST) markedly stimulated cGMP production in T84 cells. Cl- secretion across T84 cell monolayers cultured on permeable filters was stimulated by E. coli ST, cholera toxin, or 8-BrcAMP, but 8-BrcGMP was ineffective. cGMP analogues that are known to be potent and specific activators of cGMP-dependent protein kinase (cG-kinase) also had little effect on 36Cl- uptake by T84 cells cultured in plastic dishes. E. coli ST, forskolin, cholera toxin, or membrane-permeant cAMP analogues markedly increased 36Cl- uptake into T84 cells. The general protein kinase inhibitor, staurosporine, inhibited the stimulation of Cl- permeability elicited by E. coli ST, vasoactive intestinal peptide (VIP), or 8-BrcAMP. DEAE-Sephacel chromatography revealed a predominant type II isoform of cAMP-dependent protein kinase (cA-kinase) in T84 cells, whereas little or no cytosolic cG-kinase activity was found. Treatment of T84 cells with E. coli ST or VIP resulted in an increase in the cA-kinase activity ratio (-cAMP/+cAMP) if the cytosolic enzyme was assayed at reduced temperature (on ice).(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1992

Captopril enhances renal responsiveness to ANF in dogs with compensated high-output heart failure.

The systemic hemodynamic, hormonal, and renal effects of chronic angiotensin-converting enzyme inhibition (CEI) with captopril and the responses to synthetic atrial natriuretic factor (ANF) infusions in the presence and absence of captopril were examined in normal dogs (n = 6) and in dogs with an arteriovenous (AV) fistula and compensated high-output heart failure (n = 6). This experimental model is characterized by normalization of the circulating renin-angiotensin-aldosterone system (RAAS) and persistent elevations in central filling pressures and plasma ANF. In both normal and AV-fistula dogs, oral captopril for 1 wk at 35 mg.kg-1.day-1 in three divided doses produced progressive reductions in arterial and atrial pressures (P less than 0.05), plasma ANF (P less than 0.05), and aldosterone (P less than 0.05). After 1-2 days of a modest increase in urinary sodium excretion (UNaV) (P less than 0.05), all of the dogs regained and maintained sodium balance during captopril administration. On the 8th day of the captopril regimen, synthetic ANF was infused at 15 and 30 ng.kg-1.min-1 for 75-min periods each. Control infusion experiments were performed in the same animals before captopril administration. The normal dogs exhibited dose-related elevations in UNaV (P less than 0.05) that were not augmented with captopril (P greater than 0.05). In contrast, in the AV-fistula dogs the observed renal unresponsiveness to synthetic ANF in the control experiments was reversed with chronic CEI, and ANF-induced UNaV achieved levels comparable to those obtained in the normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1992

Pressure natriuresis in rats during blockade of the L-arginine/nitric oxide pathway.

The natriuretic response was studied in anesthetized rats during the intravenous infusion of L-arginine analogues to inhibit the production of endothelium-derived nitric oxide. In an initial experimental series, rats were administered saline vehicle or vehicle containing 300 mumol/kg body wt N omega-monomethyl-L-arginine, N omega-nitro-L-arginine methyl ester, N omega-monomethyl-D-arginine, or L-arginine. Infusion of the competitive inhibitors N omega-monomethyl-L-arginine and N omega-nitro-L-arginine methyl ester significantly increased mean arterial pressure to 155 +/- 3 and 145 +/- 5 mm Hg, respectively, compared with a mean arterial pressure of 118 +/- 3 mm Hg determined in the vehicle control group. Sodium excretion averaged 3.27 +/- 1.08 and 2.52 +/- 0.78 mu eq/min in the N omega-monomethyl-L-arginine- and N omega-nitro-L-arginine methyl ester-treated rats, respectively, and each was significantly higher than the basal sodium excretion of 0.20 +/- 0.05 mu eq/min in the vehicle-treated control animals. Plasma renin activity was significantly lower in the N omega-monomethyl-L-arginine- and N omega-nitro-L-arginine methyl ester-treated groups than in the vehicle-treated group. Neither L-arginine nor N omega-monomethyl-D-arginine administration significantly altered any of the measured variables compared with vehicle alone. In a second experimental series, an adjustable snare was placed around the suprarenal aorta for the purpose of controlling renal perfusion pressure independently of increases in the systemic mean arterial pressure initiated by infusion of N omega-nitro-L-arginine methyl ester (75 mumol/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Renal effects of ANF (95-126), a new atrial peptide analogue, in dogs with experimental heart failure.

Atrial natriuretic factor 95-126 [ANF (95-126)] is a novel 32 amino acid peptide which is thought to originate from the kidney. The systemic hemodynamic and renal effects of equimolar doses of intravenous synthetic ANF (95-126) and synthetic alpha ANF (99-126) were examined in normal dogs (n = 6) and in dogs with an arteriovenous (AV) fistula and chronic compensated high-output heart failure (n = 5). ANF (95-126) and alpha ANF (99-126) were infused at 5 and 10 pmol/kg/min for 75-min periods each. In the normal and AV fistula dogs the two peptides similarly decreased mean arterial pressures and right atrial pressures (P less than .05). Creatinine clearance and urinary volume excretion increased (P less than .05) in the normal dogs with both peptides, but only ANF (95-126) produced significant elevations (P less than .05) of these two parameters in the AV fistula animals. With the highest infusion dose, ANF (95-126) increased urinary sodium excretion to at least twice the levels observed with alpha ANF (99-126) in both groups of dogs (P less than .05). The decreases in plasma renin and aldosterone were comparable for the two peptides in both groups of animals. These results indicate that ANF (95-126) is more potent than alpha ANF (99-126) for the promotion of a natriuresis, particularly in AV fistula dogs with compensated high-output heart failure, in which the sodium excretory actions of alpha ANF (99-126) were attenuated markedly.

Animals↗