An outbreak vector-host epidemic model with spatial structure: the 2015-2016 Zika outbreak in Rio De Janeiro.

BACKGROUND: A deterministic model is developed for the spatial spread of an epidemic disease in a geographical setting. The disease is borne by vectors to susceptible hosts through criss-cross dynamics. The model is focused on an outbreak that arises from a small number of infected hosts imported into a subregion of the geographical setting. The goal is to understand how spatial heterogeneity of the vector and host populations influences the dynamics of the outbreak, in both the geographical spread and the final size of the epidemic. METHODS: Partial differential equations are formulated to describe the spatial interaction of the hosts and vectors. The partial differential equations have reaction-diffusion terms to describe the criss-cross interactions of hosts and vectors. The partial differential equations of the model are analyzed and proven to be well-posed. A local basic reproduction number for the epidemic is analyzed. RESULTS: The epidemic outcomes of the model are correlated to the spatially dependent parameters and initial conditions of the model. The partial differential equations of the model are adapted to seasonality of the vector population, and applied to the 2015-2016 Zika seasonal outbreak in Rio de Janeiro Municipality in Brazil. CONCLUSIONS: The results for the model simulations of the 2015-2016 Zika seasonal outbreak in Rio de Janeiro Municipality indicate that the spatial distribution and final size of the epidemic at the end of the season are strongly dependent on the location and magnitude of local outbreaks at the beginning of the season. The application of the model to the Rio de Janeiro Municipality Zika 2015-2016 outbreak is limited by incompleteness of the epidemic data and by uncertainties in the parametric assumptions of the model.

A mathematical model for indirectly transmitted diseases.

We consider a mathematical model for the indirect transmission via a contaminated environment of a microparasite between two spatially distributed host populations having non-coincident spatial domains. The parasite is benign in a first population and lethal in the second one. Global existence results are given for the resulting reaction-diffusion system coupled with an ordinary differential equation. Then, invasion and persistence of the parasite are studied. A simplified model for the transmission of a hantavirus from bank vole to human populations is then analysed.

Bradykinin B2 receptors activate Na+/H+ exchange in mIMCD-3 cells via Janus kinase 2 and Ca2+/calmodulin.

We used a cultured murine cell model of the inner medullary collecting duct (mIMCD-3 cells) to examine the regulation of the ubiquitous sodium-proton exchanger, Na+/H+ exchanger isoform 1 (NHE-1), by a prototypical G protein-coupled receptor, the bradykinin B2 receptor. Bradykinin rapidly activates NHE-1 in a concentration-dependent manner as assessed by proton microphysiometry of quiescent cells and by 2'-7'-bis[2-carboxymethyl]-5(6)-carboxyfluorescein fluorescence measuring the accelerated rate of pH(i) recovery from an imposed acid load. The activation of NHE-1 is blocked by inhibitors of the bradykinin B2 receptor, phospholipase C, Ca2+/calmodulin (CaM), and Janus kinase 2 (Jak2), but not by pertussis toxin or by inhibitors of protein kinase C and phosphatidylinositol 3'-kinase. Immunoprecipitation studies showed that bradykinin stimulates the assembly of a signal transduction complex that includes CaM, Jak2, and NHE-1. CaM appears to be a direct substrate for phosphorylation by Jak2 as measured by an in vitro kinase assay. We propose that Jak2 is a new indirect regulator of NHE-1 activity, which modulates the activity of NHE-1 by increasing the tyrosine phosphorylation of CaM and most likely by increasing the binding of CaM to NHE-1.

Weakly coupled hyperbolic systems modeling the circulation of FeLV in structured feline populations.

Global existence and regularity results are provided for weakly coupled first order hyperbolic systems modeling the propagation of the Feline Leukemia Virus (FeLV), a retrovirus of domestic cats (Felis catus). In a simple example we find a threshold parameter yielding endemic stationary states.

Role of citrate synthase in aldosterone-mediated sodium reabsorption.

Aldosterone and other mineralocorticoids increase citrate synthase activity in the kidney and enhance renal sodium reabsorption, but it is unclear whether the increased citrate synthase activity is involved in renal sodium transport. We used the Wistar-Furth rat, an inbred strain found to be deficient in renal citrate synthase activity, as an experimental model to investigate this issue. We confirmed that renal citrate synthase activity from adrenalectomized Wistar-Furth rats was decreased compared with that from control Wistar rats (by 28%). Similarly, urinary citrate excretion was 23% lower in Wistar-Furth rats. Subnormal citrate formation in Wistar-Furth rats could not be accounted for by differences in systemic pH or circulating potassium levels. Because renal citrate synthase activity was reduced in Wistar-Furth rats, we hypothesized that renal sodium excretory responses to mineralocorticoids would be reduced as well. Four-hour sodium excretion after intraperitoneal injection of 5 microg of aldosterone was reduced by 56% in adrenalectomized Wistar rats and by 52% in adrenalectomized Wistar-Furth rats (both P<0.01 compared with vehicle injection). Similarly, the pattern of urinary sodium excretion in response to subcutaneous injections of deoxycorticosterone acetate over a 2-week period was similar in adrenalectomized Wistar and Wistar-Furth rats. In summary, acute and chronic antinatriuretic responses to mineralocorticoids are maintained in Wistar-Furth rats at the level of Wistar rats, despite the marked reduction in citrate synthase activity. These findings are not consistent with an important role for citrate synthase activity in mineralocorticoid-mediated renal sodium transport.

Resistance to remnant nephropathy in the Wistar-Furth rat.

The Wistar-Furth rat, an inbred strain resistant to actions of mineralocorticoids, was used to study the concept that mineralocorticoids contribute to progressive renal injury. It was postulated that if chronic nephropathy depends on aldosterone and if Wistar-Furth rats are resistant to aldosterone, remnant nephropathy would be attenuated in Wistar-Furth rats. Wistar-Furth rats and control Wistar rats were subjected to 5/6 nephrectomy or a sham procedure and then followed for 4 wk. Renal ablation resulted in hypertension at 4 wk in both strains (164+/-5 [Wistar-Furth] versus 184+/-7 [Wistar] mm Hg mean arterial pressure), with sham animals remaining normotensive (134+/-6 mm Hg). Renal damage in response to 5/6 nephrectomy was greatly decreased in Wistar-Furth rats compared with Wistar rats. Albuminuria was markedly less in Wistar-Furth rats (12.7+/-4.2 [Wistar-Furth] versus 97.4+/-22.6 [Wistar] mg/d per 100 g body wt, P<0.01). Glomerular damage, consisting of mesangial proliferation, mesangial lysis, and segmental necrosis, was observed in 42% of glomeruli from Wistar rats but in 0% of glomeruli from Wistar-Furth rats (P<0.01). To address the possibility that higher BP in partially nephrectomized Wistar rats mediated the greater renal damage, the study was repeated, with Wistar rats (not Wistar-Furth rats) being treated with a hydralazine-reserpine-hydrochlorothiazide regimen. Although this antihypertensive regimen equalized BP (conscious systolic) (144+/-8 mm Hg [Wistar] versus 157+/-7 mm Hg [Wistar-Furth] at 4 wk), albuminuria remained more than 10-fold greater in Wistar rats. In summary, renal damage upon 5/6 nephrectomy was markedly reduced in Wistar-Furth rats, a finding not attributable to reduced systemic BP. Since Wistar-Furth rats have been shown previously to be resistant to the actions of mineralocorticoids, the data from the present study support the hypothesis that aldosterone mediates, at least in part, the renal injury attendant to renal mass reduction.

Effect of chronic bradykinin B2 receptor blockade on blood pressure of conscious Dahl salt-resistant rats.

1. In this study 3 protocols were utilized to determine the role of endogenous kinins in the resistance of the inbred Dahl (Rapp) salt-resistant (SR/Jr) rats to high salt diet-induced blood pressure elevation. 2. The bradykinin B2 receptor antagonist, Hoe 140 (D-Arg[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin) at doses of either 10-20 or 20-40 nmol day(-1) (subcutaneously (s.c), via osmotic minipumps, for either 1 or 3 weeks during a high (8%) salt diet) effectively blocked or attenuated the hypotensive responses to 100-1000 ng of bradykinin. 3. In the first protocol, 5 week old SR/Jr rats treated with Hoe 140 (10-20 nmol day(-1), n = 9, s.c., via osmotic minipumps) for 3 weeks and concomitantly fed high (8%) NaCl diet had significantly higher conscious tail cuff blood pressures (BPc) at 1 and 3 weeks when compared with rats treated with vehicle (0.9% NaCl, n = 6). The differences in BPc between the 2 groups were 13 mmHg (P < 0.001) after 1 week and 8 mmHg (P < 0.05) after 3 weeks of treatment. 4. In the second protocol, 5 week old SR/Jr rats were treated with Hoe 140 (20-40 nmol day(-1), n = 8, s.c., via osmotic minipumps) or vehicle (n = 8) for 3 weeks. During the first week of treatment the rats were fed normal (0.8%) NaCl diet. The rats were then switched to 8% NaCl for 2 remaining weeks of the protocol. The mean BPc of Hoe 140-treated rats was not significantly different from that of the vehicle-treated rats when fed 0.8% NaCl diet. In contrast, rats treated with Hoe 140 and concomitantly fed high (8%) NaCl diet had significantly increased BPc (123+/-2 vs 111 +/- 1 mmHg, P < 0.001 for the Hoe 140- and vehicle-treated rats, respectively). 5. In the third protocol, treatment with Hoe 140 (20 40 nmol day(-1), s.c., via osmotic minipumps) during high salt diet did not increase BPc in rats that were pre-exposed to the high salt diet for 2 weeks. 6. At the end of 3 weeks of study, blood pressure was measured via an arterial catheter during pentobarbitone-induced anaesthesia. Rats treated with Hoe 140 for 1 or 3 weeks had significantly lower mean arterial blood pressures than the vehicle-treated rats. 7. Our findings suggest that in SR/Jr rats, kinin activation of bradykinin B2 receptors at least partially contributes to early regulatory mechanisms that resist an increase in blood pressure following exposure to a high salt diet. The mechanism underlying the decreased blood pressure during pentobarbitone anaesthesia of SR/Jr rats chronically treated with Hoe 140 has yet to be elucidated.

Resistance to mineralocorticoids in Wistar-Furth rats.

Wistar-Furth rats (WF) do not develop hypertension when treated with salt and mineralocorticoids and therefore may be useful for investigating the mechanisms of mineralocorticoid action and hypertension. In the present studies, we determined vascular and renal responses of WF to mineralocorticoids. Control Wistar rats (W) developed deoxycorticosterone acetate (DOCA)-NaCl and dexamethasone hypertension, whereas WF rats developed dexamethasone hypertension only. Aldosterone treatment of vascular smooth muscle cells cultured from WF resulted in 82% less upregulation of angiotensin II radioligand binding, 50% less induction of angiotensin II AT1a receptor mRNA, and 76% less potentiation of angiotensin II-stimulated inositol phosphates than did aldosterone treatment of cells from W. Similarly, DOCA-NaCl potentiated angiotensin II- and phenylephrine-stimulated contractions in aortic rings from W but not from WF. Although DOCA-NaCl treatment affected hypokalemia to an equal degree in WF and W, increases in renal citrate synthase activity (a specific renal mineralocorticoid response) were greater in W than in WF. WF manifest a partial defect in mineralocorticoid responsiveness in vascular smooth muscle and, possibly, in the kidney.

Bradykinin B2 receptor antagonist increases chloride and water absorption in rat medullary collecting duct.

This study tested the hypothesis that intrarenal kinins play a regulatory role in electrolyte excretion by altering Cl- absorption in the collecting duct. We measured Cl- and insulin concentrations in tubular fluid samples obtained from medullary collecting ducts (MCD) of Dahl/Rapp salt-resistant (SR/ Jr) rats by microcatheterization of ducts of Bellini before and after treatment with the bradykinin receptor antagonist HOE-140. Tubular fluid was obtained from paired terminal inner medullary (t-IMCD) and outer medullary (OMCD) collecting duct sites of the left kidney. HOE-140 (n = 7) or vehicle (n = 5) was infused intravenously, and the collections were repeated. HOE-140 did not alter glomerular filtration rate but decreased urine flow rate (P < 0.05) and absolute and fractional Cl- excretion (P < 0.01). HOE-140 did not alter the fraction of filtered Cl- delivered (FDCl) to the OMCD but decreased FDCl to the t-IMCD from 2.3 +/- 0.3 to 1.3 +/- 0.3% (P < 0.05). The fraction of filtered Cl- absorbed per millimeter between the collection sites was increased from 0.2 +/- 0.1 to 0.6 +/- 0.1% (P < 0.05). Fractional absorption of water along the MCD was also increased (P < 0.05). No changes in excretory function or tubular Cl- or water absorption were observed in vehicle-treated rats. These studies show that kinin B2 receptor blockade enhances Cl- and water absorption in the MCD, a finding that supports a role of renal kinins in the regulation of NaCl and water excretion.

Effect of dietary protein and enalapril on proximal tubular delivery and absorption of albumin in nephrotic rats.

In passive Heymann nephritis (PHN), angiotensin-converting enzyme inhibition (ACEI) or a low dietary protein intake decreases albuminuria (UAlbV). Although this reduction in albuminuria appears to result from an improvement in glomerular permselectivity, the effect of these treatments on albumin permeation and absorption by the nephron has not been clarified. This study used micropuncture techniques to examine the effect of these two treatments on albumin permeation (by measuring the delivery of albumin to the proximal tubule) and the tubular absorption of albumin. PHN rats (12-18 days after injection of FX1A) were switched from 23% to either 40% protein diet (HP), 40% protein diet and concomitantly treated with enalapril (40 mg.kg-1.day-1) (HPE), or to 8% (LP) protein diet for 4-6 days. Although left kidney glomerular filtration rate (GFR) did not differ among the groups, UAlbV from the left kidney in LP and HPE was only 20-40% of that observed for the HP group. In protocol 1, the fractional recovery of albumin (FRAlb) in urine was calculated following injection of artificial tubular fluid containing [14C]inulin and 125I-labeled albumin into the earliest identifiable proximal loops. There were no differences in FRAlb among the three groups. In protocol 2, timed quantitative collections of tubular fluid were obtained from proximal tubular loops. The rate of albumin delivery to the earliest accessible loops of the proximal tubule was significantly lower for the LP and HPE groups compared with the HP group. For each group, albumin concentration corrected for water absorption was not altered along the proximal tubule. The data indicate that alterations of dietary protein intake or ACEI treatment results in large changes in the delivery of albumin at the proximal tubule that could singularly account for the changes in urinary albumin excretion.

Role of kinins in the renal response to enalaprilat in normotensive and hypertensive rats.

This study examined the role of endogenous kinins in the alteration of renal hemodynamics induced by low-dose converting enzyme inhibition in hydropenic normotensive rats and in the nonclipped kidney of hydropenic two-kidney, one clip hypertensive rats. Infusion of a bradykinin B2 receptor antagonist (D-Arg0,[Hyp3,Thi5,8,D-Phe7]-bradykinin, 1 or 10 micrograms.kg-1.min-1) did not alter renal function of normotensive rats. In a second series of experiments, infusion of enalaprilat at 0.1 mg.kg-1.h-1 increased renal blood flow (P < .01) and decreased renal vascular resistance (P < .01). The superimposition of the kinin antagonist at 1 micrograms.kg.min-1 during the enalaprilat infusion decreased renal blood flow to a value similar to the preenalaprilat baseline and significantly different from the mean of the two enalaprilat periods before and after the addition of the kinin antagonist--the "mean effect of enalaprilat." The decrease in renal blood flow induced by the kinin antagonist was associated with an increase in renal vascular resistance above the mean effect of enalaprilat (P < .025). In two-kidney, one clip hypertensive rats, systemic infusion of enalaprilat augmented the hemodynamics of the nonclipped kidney by a degree similar to that in normotensive rats. In contrast to normotensive rats, superimposition of the kinin antagonist did not alter the enalaprilat-induced change in blood flow or vascular resistance of the nonclipped kidney. The results of this study suggest that endogenous kinins contribute to the increased renal function induced by low-dose converting enzyme inhibition in hydropenic normotensive rats but appear to contribute less to the enalaprilat-induced alterations of renal function in the nonclipped kidney of two-kidney, one clip hypertensive rats.

Diffusion epidemic models with incubation and crisscross dynamics.

A diffusion age-structured epidemic model is analyzed. The model describes an epidemic in a host-vector two-population system. Each population is diffusing in a spatial region. Each population is divided into susceptible, incubating, and infectious subclasses. The incubating and infectious subclasses in each population are determined by a structure variable corresponding to age since infection. The model consists of a system of nonlinear partial differential equations with crisscross dynamics. The existence, uniqueness, and asymptotic behavior of solutions are analyzed.

Effects of chronic treatment with angiotensin converting enzyme inhibitor or an angiotensin receptor antagonist in two-kidney, one-clip hypertensive rats.

The effects of chronic angiotensin II (Ang II) receptor blockade (losartan) or converting enzyme inhibition (enalapril) on blood pressure (BP), urinary albumin excretion (Ualb V), renal histology and the hemodynamic and excretory function of the clipped and nonclipped kidneys were studied in two-kidney, one-clip (2-K 1-C) rats. One day after clipping the right renal artery, male Wistar rats were divided into three groups receiving: (1) losartan, 20 mg/kg/day (N = 7), (2) enalapril, 20 mg/kg/day (N = 8), or (3) no treatment (controls, N = 9) for three weeks. Both losartan and enalapril treatments maintained conscious BP at comparably lowered levels compared to control animals (116 +/- 6 mm Hg and 113 +/- 2 mm Hg vs. 188 +/- 11 mm Hg, respectively, P < 0.01). Treatment also prevented the increase in Ualb V, observed for the untreated group, three weeks after clipping (1.7 +/- 0.5 and 0.7 +/- 0.1 mg/24 hr vs. 17.8 +/- 7 mg/24 hr, respectively, P < 0.01). After three weeks of treatment, acute study of renal function during pentobarbital anesthesia revealed higher values of GFR and RPF and lowered vascular resistance for nonclipped kidneys from the losartan and enalapril groups compared to the corresponding kidneys from control animals. Despite the lower BP of both treated groups, clipped kidney GFR and RPF were unchanged compared to the control group. Ualb V for nonclipped kidneys from untreated rats was approximately 5- to 10-fold higher than in the nonclipped kidneys from the treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathophysiology of altered renal function in renal vascular hypertension.

It is now clear that specific angiotensin-dependent mechanisms contribute importantly to the pathophysiology of hypertension (HT) and altered renal function in models of two-kidney, one-clip (2-K, 1-C) HT in rats. The discovery of specific antagonists for angiotensin-converting enzyme and the newer angiotensin receptor and kinin receptor antagonists have allowed delineation of the contributions of these hormones to altered renal function in these models. The focus of interest in most of these studies has been the nonclipped kidney, which would be expected to ameliorate elevated blood pressure by exhibiting a pressure diuresis and natriuresis in the environment of systemic HT. Antagonism of the renin-angiotensin system in rat models of renal vascular HT indicates that the effects of angiotensin attenuate renal hemodynamic and excretory behavior, particularly in the nonclipped kidney. Furthermore, angiotensin attenuates the efficiency of autoregulation of renal hemodynamics in the nonclipped kidney. Function of the clipped kidney appears to be both angiotensin and perfusion pressure dependent. Evidence that inhibition of angiotensin reverses or improves these altered hemodynamic and excretory functions indicates that angiotensin may contribute importantly to the pathophysiology of HT in these models by altering or impairing the ability of the nonclipped or "normal" kidney to excrete sodium and volume. The precise roles of altered activity of vasodilator hormones to contribute to these alterations of renal function remains to be defined.

Kinins as vasoactive peptides.

During the past year, a number of significant publications have provided data that clearly establish the basis for the important role of the tissue kallikrein-kinin system in cardiovascular control and renal function. These publications include a report of advances in techniques for system component measurement, reports of the localization of central bradykinin receptors and an alteration in the sensitivity of the central bradykinin system in hypertension, and a description of the effects of new kinin receptor antagonists on our understanding of endogenous and exogenous kinin-induced vasorelaxation and its possible alteration in hypertension. Several significant reports describe the potentiation of endogenous kinin action by kininase inhibitors and establish the important interaction between kininase activity and kinin control of blood pressure.

Urodilatin: binding properties and stimulation of cGMP generation in rat kidney cells.

Urodilatin (URO) [ANP-(95-126)] is an analogue of atrial natriuretic peptide (alpha-ANP) [ANP-(99-126)] that was first isolated from human urine. In rat mesangial cells, URO competed with high affinity for non-guanylate cyclase-coupled ANPR-C receptors [concentration at which 50% labeled ligand is displaced (IC50) approximately 70 pM], but with lesser affinity to the guanylate cyclase-linked ANPR-A receptors (IC50 approximately 800 pM). alpha-ANP bound to both receptors with similar affinity [dissociation constant (Kd) approximately 150 pM]. In papillary collecting duct homogenates, which possess only ANPR-A receptors, the apparent Kd value averaged 229 pM for alpha-ANP and 2.7 nM for URO. Intravenous URO was at least as potent and effective as alpha-ANP in inducing diuresis and natriuresis in anesthetized rats, but URO was approximately 10-fold less potent in stimulating guanosine 3',5'-cyclic monophosphate generation in mesangial and inner medullary collecting duct cells. We conclude that URO has a lesser affinity than alpha-ANP for guanylate cyclase-coupled ANP receptors in the kidney and that the relative natriuretic potency of URO in vivo cannot be directly attributed to its binding characteristics with ANPR-A receptors.

Effect of pH on vasopressin-induced water permeability in collecting ducts of isolated rat papillae.

1. The effects of basolateral and luminal pH on diffusional water permeability of microperfused collecting ducts of isolated rat papillae were examined in the presence and absence of vasopressin at two concentrations. 2. In the absence of vasopressin, collecting duct diffusional water permeabilities did not differ when the pH of the luminal fluid was varied. Similarly, in the absence of vasopressin, collecting duct diffusional water permeabilities did not differ when the bath pH was varied. 3. In the presence of 50 microU/ml vasopressin, increases in diffusional water permeability of collecting ducts perfused with solutions at pH 5.0, 7.4 or 9.0 did not differ significantly. Similarly, increases in diffusional water permeability induced by 200 microU/ml vasopressin were not different when collecting ducts were perfused with solutions at pH 5.0, 7.4 or 9.0. 4. The presence of vasopressin (50 microU/ml) in the bathing medium at pH 6.4, 7.4 and 8.4 induced increments in diffusional water permeability of 0.40 +/- 0.21 (n = 14, P greater than 0.05), 1.56 +/- 0.27 (n = 27, P less than 0.001) and 1.67 +/- 0.24 (n = 12, P less than 0.001) microns/s, respectively. The increment in water permeability at pH 6.4 was significantly less than that at pH 7.4 (P less than 0.001). 5. The presence of vasopressin (200 microU/ml) in the bathing medium at pH 6.4, 7.4 and 8.4 induced increments in diffusional water permeability of 2.16 +/- 0.54 (n = 9, P less than 0.01), 2.55 +/- 0.51 (n = 17, P less than 0.001) and 0.98 +/- 0.34 (n = 11, P less than 0.05) microns/s respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of atrial peptide on collecting duct function.

1. The effects of synthetic rat atrial natriuretic peptides (ANP) on diffusional 22Na+, 36Cl- and tritiated water (THO) permeability of in vitro microperfused rat papillary collecting ducts and the effect in vivo of ANP on stop-flow sodium concentrations in the terminal segment of rabbit nephrons were studied. 2. The addition of 4 x 10(-8) or 4 x 10(-7) mol/l ANP to the medium or perfusion solution did not alter diffusional 22Na+ or 36Cl- permeability of microperfused rat papillary collecting ducts. 3. The basal diffusional THO permeability of papillary collecting ducts was not altered when 4 x 10(-7) mol/l ANP was present in the medium and did not inhibit the increment in diffusional THO permeability induced by vasopressin or reduce the permeability to water in a duct previously stimulated by vasopressin. 4. The administration of ANP (2 micrograms/kg bodyweight) to rabbits in water diuresis did not alter systemic blood pressure but induced a marked natriuresis and increases in urine flow and potassium excretion. This natriuresis was not associated with alterations in stop-flow sodium reabsorptive capacity or sodium permeability of the collecting tubules and ducts. 5. Previously reported in vivo clearance data suggest that ANP causes, at least in part, a natriuresis by altering sodium transport in the medullary collecting ducts. In this study, however, a direct effect could not be demonstrated and it is possible that the medulla needs to be functioning in its normal environment for such effects to be demonstrated.

Effect of atrial natriuretic peptide on collecting duct function evaluated by stop-flow in rabbits.

1. The effect of a low dose of a synthetic atrial natriuretic peptide (ANP), rat atriopeptin II (23 amino acids), on stop-flow sodium concentrations was examined in rabbits in water diuresis. 2. Atrial natriuretic peptide (2 micrograms/kg body weight) was injected intravenously as a bolus either before or after the commencement of stop-flow. 3. Atrial natriuretic peptide induced a significant natriuresis within 2 min of injection. This natriuresis was associated with smaller increases in urine volume and potassium excretion. Atrial natriuretic peptide did not alter blood pressure. 4. Atrial natriuretic peptide did not significantly alter stop-flow sodium concentrations. 5. These findings indicate that ANP does not directly alter sodium transport across medullary collecting ducts. 6. It is proposed that ANP acts via a mediator to alter sodium movement across terminal segments of the nephron.