2-bromoethylamine Hydrobromide Research Articles

Alkylderivatives of Stanna- closo-dodecaborate

The reactions of [SnB 11H 11] 2− with organic halides like 1-chloro-3-iodopropane, allylbromide, propargylbromide and 2,6-bis-(bromomethyl)pyridine lead in a nucleophilic substitution at room temperature to the products [Bu 3MeN][Cl(CH 2) 3SnB 11H 11] ( 4), [Bu 3MeN][H 2CCHCH 2SnB 11H 11] ( 6), [Bu 4N][HCCCH 2SnB 11H 11] ( 7), and [Bu 4N] 2[2,6-(H 11B 11SnCH 2) 2(C 5H 3N)] ( 8). In water Na 2[SnB 11H 11] reacts with 2-bromoethylamine hydrobromide at 50 °C and 3-bromopropylamine hydrobromide at 70 °C to the zwitterionic products [H 11B 11Sn(CH 2) n NH 3] ( n=2, 3), which were characterized by X-ray crystal structure analysis. [H 11B 11Sn(CH 2) 2NH 3] crystallizes with one equivalent of water under the formation of NHO hydrogen bonding. In the case of chloroiodomethane and diiodomethane the substitution reaction proceeds differently and the monosubstituted components were not detected. The disubstituted compound [Bu 3MeN] 2[H 2C(SnB 11H 11) 2] ( 5), whose structure could be confirmed by X-ray crystal structure analysis, is the only observed reaction product.

Synthesis and QSAR Studies in 2-( N-aryl- N-aroyl)amino-4,5-dihydrothiazole Derivatives as Potential Antithrombotic Agents

A series of 2-( N-aryl- N-aroyl)amino-4,5-dihydrothiazole derivatives have been synthesized via cyclocondensation of N-aryl thioureas with 2-bromoethylamine hydrobromide followed by the reaction of the product thus obtained with aroyl chlorides. Title compounds were evaluated for their antithrombotic activity in vivo in mice where one of these compound 29 provided 65% protection as compared to 77% protection offered by the standard Indomethacin. Quantitative Structure–Activity Relationship (QSAR) studies were performed on these compounds using physicochemical (hydrophobic, electronic, steric) parameter as independent and antithrombic activity as dependent parameter, where antithrombotic activity correlated best ( r>0.8) with electronic parameters ( F , σ or μ) having high statistical significance >99.9% (F 2,22>15.0; F 2,22α:0.001=11.0) suggesting that hydrophobic, steric and resonance factors are insignificant in this set of molecules for the activity.

Natriuresis obtained by intracerebroventricular infusion of hypertonic NaCl in rats with papillary necrosis.

Raising the sodium concentration in the third cerebral ventricle increases renal sodium, potassium and water excretion. The identification and characterization of the factor(s) mediating the centrally evoked natriuresis would be greatly facilitated if the exact intrarenal effector site were known. We have assessed the importance of inner medullary structures for the effects of CNS stimulation by examining its ability to alter renal excretion in rats with papillary necrosis, induced 2 d earlier with 2-bromoethylamine hydrobromide (BEA), 250 mg kg-1 body wt i.v. Male Lewis x DA rats were divided into a BEA-treated group (n = 6) and a control group receiving vehicle alone (n = 6). In contrast to the white papillae normally seen, the papillae of BEA-treated animals were bright red and showed a clear line of demarcation at their base. The rats were anaesthetized i.p. with Inactin (120 mg kg-1 body wt). Artificial cerebrospinal fluid (CSF) was infused (520 nL min-1) via a cannula into the left lateral ventricle. After 45 min CSF containing 1 M NaCl was used. Stimulation of the control rats with hypertonic CSF increased urine flow rate five-fold (5.4 +/- 0.8 to 27.1 +/- 6.1 microL min-1), Na excretion 23-fold (0.4 +/- 0.1 to 7.6 +/- 1.8 mumol min-1) and K excretion fourfold (0.6 +/- 0.18 to 3.8 +/- 0.5 mumol min-1). When the concentration mechanisms were damaged with BEA, the basal excretion rates of water and Na increased. The natriuretic response to ICV stimulation was severely impaired in these rats, but the kaliuretic effect was sustained.(ABSTRACT TRUNCATED AT 250 WORDS)

2-substituted thioadenine nucleoside and nucleotide analogues: synthesis and receptor subtype binding affinities (1).

The design, synthesis, and receptor subtype binding affinities of several 2-substituted thioadenosine nucleoside and nucleotide analogues are described. Alkylation of 2-thioadenosine (1) with iodopentenylboronic acid followed by iododeboronation gave 2-((E)-1-iodo-1-penten-5-yl) thioadenosine (9). Compound 1 on treatment with 4-nitrobenzyl bromide and propargyl bromide furnished compounds 3 and 5, respectively. The 5'-monophosphate analogues of compounds 3, 5, 7, and 9 were prepared similarly using 2-thioadenosine 5'-monophosphate (2). Treatment of 1 with bromoethylamine hydrobromide provided 2-[(aminoethyl)thio]adenosine (11) which on coupling with N-succinimidyl 3-(4-hydroxyphenyl)propionate gave 2-[[[3-(4-hydroxyphenyl)propionamido]ethyl]thio]adenosine (12). Iodination of 12 gave 2-[[[3-(4-hydroxy-3-iodophenyl)propionamido]ethyl]thio]adenosine (13). Compounds 3-13 were evaluated for their affinities toward A1 and A2 adenosine receptors in rat brain cortex and striatum, respectively using [3H]DPCPX and [3H]CGS21680 as ligands. The nucleotide analogues 4, 6, 8, and 10 inhibited binding of [3H]DPCPX by 10-20% and of [3H]CGS21680 by 40-50% at a concentration of 100 microM suggesting weak affinity toward adenosine receptors. The nucleoside analogues 3, 5, 7, 9, 12, and 13 inhibited the A2 receptor binding of [3H]CGS21680 with Ki values of 1.2-3.67 microM, while A1 receptor binding of [3H]DPCPX was inhibited with Ki values 10-17 microM. The A1/A2 ratios suggest 4-8-fold A2 receptor selectivity.

Long-Term Effects of Enalapril in Rat with Experimental Chronic Tubulo-interstitial Nephropathy

The aim of this study was to determine whether or not angiotensin-converting enzyme inhibitor, enalapril, could ameliorate the chronic tubulo-interstitial nephropathy (TIN) in uninephrectomized (UNx) rats. Chronic TIN(M) was induced by 2-bromoethylamine hydrobromide. Rats were assigned to five groups; control, UNx-control (UNxC), UNx treated with enalapril (UNxE), UNxMC and UNxME. Enalapril was given for 12 months as drinking water (50 mg/l). At 6 months, albuminuria in UNxE decreased significantly compared with UNxC, but without change in UNxM rats. By 12 months, although all rats in control, UNxC and UNxE remained alive, 1 and 4 rats died in UNxME and UNxMC, respectively. Albuminuria in UNxC was reduced significantly by enalapril but not in UNxM rats. Both urine volume and urine osmolality became equal to control by enalapril in UNx rats, but not in UNxM rats. Serum cholesterol levels were normalized by enalapril in UNx rats, but not in UNxM rats. Levels of serum creatinine and blood urea nitrogen were invariably higher in UNxM than in UNx rats, irrespective of enalapril. Glomerular sclerosis was statistically decreased by enalapril in both UNx and UNxM rats. Enalapril reduced the overall tubulo-interstitial lesions in UNx rats, but not in UNxM group. However, in UNxM rats tubular changes in medullary portion were significantly ameliorated by enalapril. These data suggest that enalapril has a beneficial effect on chronic TIN in this model.

Early sequential ultrastructural renal alterations induced by 2-bromoethylamine hydrobromide in the Swiss ICR mouse.

Thirty-two male Swiss ICR mice were injected intraperitoneally with 300 mg 2-bromoethylamine hydrobromide/kg body weight, anesthetized, and perfused with glutaraldehyde-paraformaldehyde solution at 5, 15, 30, 60, 90, 120, 150, and 180 minutes after treatment. Eight control mice were injected intraperitoneally with sterile diluent, and one was perfused at each of the same time periods as the treated mice. Proximal tubule epithelial alterations progressed over time from increased secondary lysosome and myeloid body formation to cellular and mitochondrial swelling and eventually cell necrosis. The glomerular, peritubular, and vasa recta capillaries had endothelial cell swelling and desquamation and platelet aggregation. Bromoethylamine nephrotoxicosis in the male Swiss ICR mouse is an ischemic necrosis of the proximal tubules and papilla initiated by endothelial cell damage and makes an excellent model of chemically induced damage to endothelial cells and tubular necrosis.

Influence of the renal medulla and early treatment with enalapril upon the development of hypertension in young spontaneously hypertensive rats.

To investigate the role of the renal medulla in early hypertension in spontaneously hypertensive rats (SHR), and to explore whether the attenuated increase of pressure induced by enalapril treatment is affected by chemical medullectomy. Forty-four male SHR were studied from 5 to 18 weeks of age: 22 remained intact; 22 were medullectomized at 5.5 weeks of age with 2-bromoethylamine hydrobromide; 11 of each of these two groups were treated with enalapril from 6 to 12 weeks of age. Blood pressure, heart rate and body weight were recorded intermittently, and at 18 weeks renal function was also analysed. The results indicate a protective effect of the renal medulla against severe pressure rises in SHR, although even when enalapril also lowered blood pressure in medullectomized SHR, persistent improvements of glomerular filtration rate and renal flow conductance occurred only in intact SHR. Furthermore, after enalapril treatment ended blood pressure rose to higher levels in medullectomized SHR, despite greater sodium-water losses. The renal medulla seems to exert a protective role both during and after enalapril treatment.

Experimental renal papillary necrosis in the Mongolian gerbil (Meriones unguiculatus).

Sequential light microscopic and ultrastructural examination of kidneys from male and light microscopic examination of female Mongolian gerbils given 250 mg 2-bromoethylamine hydrobromide (BEA)/kg body weight ip were performed. In addition, male Mongolian gerbils were treated with both BEA and ip injections of either water, dimethyl sulfoxide, piperonyl butoxide, or reserpine. Light microscopic renal lesions in male Mongolian gerbils progressed from congestion of the vasa recta of the proximal inner medulla at 6 hr post-treatment to total renal papillary necrosis (RPN) at 24 hr post-treatment. There was no sex difference in sensitivity to BEA. Ultrastructural alterations in male gerbils were restricted to the vasa recta. Vascular lesions of endothelial swelling and pericapillary edema in the vasa recta of the proximal inner medulla was observed 2 hr post-treatment and progressed to occlusion by platelets adherent to exposed basement membranes at 6 hr post-treatment. Diuresis induced by injections of saline and injections of dimethyl sulfoxide or piperonyl butoxide did not affect the development of BEA-induced RPN. Reserpine slowed the development of BEA-induced RPN by its vasodilatory effect on the renal vasculature, not by blocking the endothelial toxicity of BEA. RPN induced by BEA in the Mongolian gerbil is apparently an ischemic necrosis of the inner medulla that develops secondary to endothelial damage of the vasa recta.

Chemical renal medullectomy and arterial pressure response to sinoaortic denervation.

We investigated in conscious Wistar-Kyoto rats the effect of chemical renal medullectomy on the responses of mean arterial pressure, arterial pressure lability, and heart rate to sinoaortic deafferentation (SAD). Chemical medullectomy was obtained by the intravenous administration of 2-bromoethylamine hydrobromide (2-BEA) 2-3 weeks before SAD or sham SAD. Chemically medullectomized rats were compared with control rats treated with saline. In control rats, the increase in mean arterial pressure elicited by SAD was not significantly greater than that produced by sham SAD. In medullectomized rats, SAD significantly increased mean arterial pressure compared with sham SAD. No direct relation was observed between the response of mean arterial pressure to SAD and the grade (1, 2, or 3) of lesion of the renal papilla. In control rats, SAD increased significantly arterial pressure lability. Chemical medullectomy did not affect basal lability or the increased lability after SAD. No direct relation was observed between increased arterial pressure lability due to SAD and the grade of lesion of the renal papilla. SAD produced a conspicuous tachycardia in control rats. Chemical medullectomy did not affect basal heart rate or the tachycardia produced by SAD. No direct relation was observed between the extent of this tachycardia and the grade of lesion of the renal papilla. These data indicate that lesions of the renal papilla lead to a significant increase in mean arterial pressure after SAD, without affecting basal pressure or heart rate. In addition, SAD per se did not increase significantly the mean arterial pressure in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for a renomedullary vasodepressor system in rabbits and dogs.

Renal perfusion was increased in anesthetized rabbits and dogs by using an extracorporeal circuit. When left kidney perfusion pressure was raised in rabbits (145-240 mm Hg), arterial pressure fell by 1.34 +/- 0.20 mm Hg/min. Pretreatment of the rabbits with 2-bromoethylamine hydrobromide, which destroyed the renal medulla, abolished the fall in arterial pressure (-0.08 +/- 0.08 mm Hg/min) in response to increased renal perfusion pressure. In dogs (with blockade of autonomic ganglia by pentolinium, converting enzyme inhibition [captopril/enalaprilat], and surgical renal denervation), increasing renal perfusion pressure to 170-220 mm Hg resulted in a fall in arterial pressure by 0.32 +/- 0.03 mm Hg/min (or by 28.9 +/- 3.1 mm Hg over a 90-minute period). Mean arterial pressure did not change significantly in identically prepared dogs not subjected to increased renal perfusion pressure, whereas pretreatment of dogs with bromoethylamine abolished the hypotensive response to increased renal perfusion pressure. Thus, the hypotensive response to increased renal perfusion was dependent on the presence of an intact renal medulla, but hypotension still occurred in the presence of converting enzyme inhibition, autonomic ganglion blockade, and renal denervation. The results provide in vivo evidence in two species that a vasodepressor factor from the renal medulla is released in response to increased renal perfusion.

Magnetic resonance microscopy of toxic renal injury induced by bromoethylamine in rats

The alkylhalide 2-bromoethylamine hydrobromide (BEA) produces renal injury in rats that mimics analgesic-related renal injury in humans. Our purpose was to examine this injury, in vivo in rats, with magnetic resonance (MR) microscopy and correlate MR findings with findings from light microscopy of hematoxylin-eosin-stained sections. Rats ( n = 48) were injected intravenously with BEA (150 mg/kg) or saline and imaged with MR 6, 48, and 336 hr later. The spin-spin relaxation time, T 2, was measured from the cortex to the papilla. In other rats, we measured regional water content of the kidney. Renal injury was present 48 and 336 hr after BEA dosing based on increased renal organ weights, decreased urine specific gravity, and significant renal lesions (H & E). T 2 was elevated in the inner stripe of the outer medulla in injured kidneys at 48 hr. The differences in T 2 between cortex and outer medulla were also elevated 48 hr after BEA. In the inner medulla, there were no changes in T 2 after BEA treatment. However, in all groups there were significant regional differences in T 2. The value of T 2 increased from outer to inner medulla and this gradient was directly correlated with water content. Thus, MR microscopy detected damage in the outer medulla after BEA injury but not the damage in the inner medulla. T 2 appeared to reflect the water content in the different regions of the medulla. The noninvasive in vivo capability of MR microscopy, with its high sensitivity to tissue water, allows the toxicologist to monitor the progression and regression of toxic insult in the same animal. At present the technology is complicated. The precise and accurate measure of MR-sensitive parameters in live animals at microscopic resolution is difficult. However, as the technology matures, there will be significant improvements providing the toxicologist a unique in vivo tool.

Effects of reserpine and l-cysteine and glutathione depletion on 2-bromoethylamine hydrobromide-induced tubular necrosis in Swiss ICR mice

Female Swiss ICR mice were injected ip with 100 or 300 mg 2-bromoethylamine hydrobromide (BEA)/kg body weight. Male Swiss ICR mice were subjected to water deprivation, or treated with 5% dextrose in water, dimethylsulphoxide, piperonyl butoxide, SKF-525A, sodium phenobarbital, β-naphthoflavone, probenecid, reserpine, diethyl maleate, buthionine sulphoximine or l-cysteine. Urine collected sequentially from male Swiss ICR mice given 300 mg BEA/kg body weight was analysed for glucose, protein, pH and specific gravity. Female mice were less sensitive to BEA than were male mice. Diuresis, antidiuresis, treatment with cytochrome P-450 inducers and inhibitors, and the antioxidant dimethylsulphoxide had no effect on the incidence or severity of tubular necrosis (TN) induced by BEA. Probenecid and l-cysteine decreased the severity, but they had no effect on the incidence of TN. Glutathione depletion by diethyl maleate and inhibition of glutathione synthesis by buthionine sulphoximine decreased the dose of BEA necessary to cause TN; buthionine sulphoximine was more effective than diethyl maleate. Reserpine decreased both the incidence and severity of TN. Glycosuria, aciduria and decreased urinary specific gravity occurred before morphological changes were seen under the microscope, indicating that the functional changes precede the morphological changes. These data indicate that glutathione is important in protecting against BEA-induced TN, that BEA or a metabolite is concentrated in the tubule epithelium by way of anion transport, and that vasoconstriction contributes to the development of BEA-induced TN.

One-Pot Synthesis of 4-Substituted 2-Thio-5-oxo-1,3,6-thiadiazaoctane

Abstract 4-Substituted 2-thio-5-oxo-1,3,6-thia-diazaoctanes have been prepared in one pot by the reaction of α-amino acid aster hydrochlorides with carbon disulfide and 2-bromoethylamine hydrobromide in the presence of triethylamine.

Vascular capacitance in rats subjected to chemical renal medullectomy.

Selective renal medullary destruction is produced in rats by a single injection of 2-bromoethylamine hydrobromide. The object of these studies was to investigate whether destruction of the renal medulla in normal rats would alter vascular capacitance. Conscious bromoethylamine-treated rats (n = 15) were compared with control saline-injected rats (n = 12). Mean circulatory filling pressure was measured during a brief circulatory arrest caused by inflation of a right atrial balloon. Blood volume was determined from plasma volume (iodine-125-labeled albumin) and hematocrit. Mean circulatory filling pressure was measured at resting blood volume and after rapid blood volume changes. Vascular compliance was derived from the mean circulatory filling pressure-blood volume curve. The bromoethylamine-treated rats were significantly hypertensive compared with control rats (mean arterial pressure 133 +/- 2 and 114 +/- 3 mm Hg, respectively, p less than 0.001) and had a significant tachycardia (475 +/- 8 and 443 +/- 10 beats/min, respectively, p = 0.02). Blood volume, plasma volume, hematocrit, and sodium excretion were no different. There was no significant difference in mean circulatory filling pressure (6.5 +/- 0.2 and 6.8 +/- 0.2 mm Hg, respectively, p = 0.4) or vascular compliance (3.64 +/- 0.20 and 3.53 +/- 0.12 ml/kg/mm Hg, respectively, p = 0.7). The position of the vascular pressure-volume curve was unchanged indicating no change in vascular capacity. This would suggest that the destruction of renal medullary vasodepressor mechanisms does not result in alterations in vascular capacitance.

Acute cortical tubular necrosis in the swiss ICR mouse induced by 2-bromoethylamine hydrobromide

Dose-response and sequential studies of 2-bromoethylamine hydrobromide (BEA) nephrotoxicosis were carried out using Swiss ICR mice. For the dose-response study, 150 male mice, 30 per group, were injected intraperitoneally (ip) with 100, 200, 300, 400 or 500 mg BEA/kg and ten from each group were killed 1, 3 or 5 days after treatment. For the sequential study, 80 male mice were injected ip with 300 mg BEA/kg and ten were killed at 0.5, 1, 2, 3, 6, 12 or 18 hr, or 10 days after treatment. Control mice (10–15) in both studies were given 0.15 ml of 0.9% NaCl solution injected ip and were killed after 1, 3 or 5 days in the former study and after 18 hr or 10 days in the latter study. Mortality and the extent of the renal lesions were dose dependent. The percentage of mice with tubular necrosis varied from 0 in mice given 100 mg BEA/kg to 100 in mice given 400 mg BEA/kg. The percentage of mice with renal papillary necrosis was also dose dependent and varied from 0 in the 100 mg/kg group to 72 in the 400 mg/kg group. Degeneration of proximal tubules was detected 2 hr after treatment. Three hours after treatment, grossly, the renal cortex was diffusely pale and, microscopically, there was marked acute tubular necrosis. Epithelial cells lining the cortical tubules were regenerating 3 days after treatment. By 10 days after treatment cortical interstitial fibrosis was marked with many tubules lined by regenerating epithelium and many tubules were dilated. BEA-induced nephrotoxicosis in the mouse was primarily an acute cortical tubular necrosis.

Neural-Renal Interactions in the Hypertension Induced by Papillary Necrosis: Role of Dietary Salt Intake

The effects of high salt intake (1.0% NaCl in the drinking water) on rats made hypertensive by 2-bromoethylamine hydrobromide (BEA) treatment (200 mg/kg, i.p.) were examined. BEA-induced medullary necrosis resulted in a mild hypertension (146 +/- 5 mm Hg) that was exacerbated by 4 weeks of high salt intake (163 +/- 6 mmHg). BEA-treated rats had significant salt-induced increases in urinary norepinephrine excretion and hypothalamic and brainstem norepinephrine content, that were not present in BEA-treated rats drinking tap water or control rats drinking saline. BEA treatment in combination with increased salt intake produced a decrease (p less than 0.05) in renal dopamine content and adrenal norepinephrine stores relative to BEA treatment alone. BEA treatment also significantly decreased renal norepinephrine stores and dopamine binding sites irrespective of salt intake. Renal alpha 2-adrenergic receptors and central nervous system stores of dopamine and serotonin were unaffected by BEA treatment. Renal function was well preserved as indicated by normal creatinine, glucose and protein excretion; however, significant (p less than 0.05) disruption of the urinary concentrating mechanism was present. These studies suggest that BEA-induced hypertension has a neural component that is exacerbated by high salt intake. The primary defect in BEA hypertension appears to be the lack of circulating antihypertensive lipids that attenuate the ability of salt loads to simulate sympathetic nervous system activity.

Renal necrosis and the involvement of a single enzyme of the de novo pathway for the biosynthesis of platelet-activating factor in the rat kidney inner medulla

2-Bromoethylamine hydrobromide (BEA), when administered to rats, induces a highly specific papillary necrosis associated with the inner medulla. PAF levels in the blood were lowered by 50% and of the three enzymes that comprise the de novo route for PAF in the cortex/medulla, only the cholinephosphotransferase activity in the inner medulla microsomes was reduced (33%) by the BEA treatment. Moreover, BEA did not affect phosphatidylcholine synthesis in either the cortex or inner medulla. Our studies indicate that the de novo pathway for PAF synthesis in the renal inner medulla is responsible for the secretion of newly formed PAF into the blood stream and that a single enzyme in the de novo route accounts for the decreased rate of PAF synthesis during the development of renal necrosis.

Evidence for a decreased noradrenaline sensitivity in mesenteric resistance vessels from rats with chemical renal medullectomy.

1. Chemical renal medullectomy was performed in Wistar rats by intraperitoneal injection of 2-bromoethylamine hydrobromide (200 mg/kg body weight). The effect of this treatment upon blood pressure and mesenteric vascular reactivity and morphology was studied 3 weeks after treatment. 2. Blood pressure was significantly raised in medullectomized rats. The indirect systolic pressures (means +/- SEM) were 112 +/- 2.4 mmHg (14.9 +/- 0.32 kPa) and 123 +/- 3.5 mmHg (16.4 +/- 0.5 kPa) (P less than 0.02) for control (n = 12) and medullectomized (n = 12) rats, respectively. However, there were no significant changes in the morphology of the mesenteric resistance vessels. 3. Maximum pressor responses and Ca2+ sensitivities were unchanged in these vessels compared with controls, but the sensitivity to noradrenaline was significantly reduced. Noradrenaline pD2 (= -log ED50) values (means +/- SEM) were 5.87 +/- 0.03 and 5.69 +/- 0.08 (P less than 0.05) for control (n = 12) and medullectomized (n = 12) rats, respectively. 4. This study demonstrates that in this model of hypertension the noradrenaline sensitivity is reduced in mesenteric resistance vessels, but there are no detectable morphological changes associated with the rise in blood pressure.

Natriuretic response to hypervolemia is absent in rats with papillary necrosis

The renal responses to acute expansion of the blood volume (20%), acute saline loading (5% body wt), or administration of atrial natriuretic peptide (ANP) were investigated in rats 7-10 days after inducing experimental renal papillary necrosis by the injection of bromoethylamine hydrobromide. In normal rats, urinary Na output (UNaV) increased from 1 +/- 0.4 to 16.6 +/- 1.7 mumol/min. In rats with papillary necrosis, UNaV only increased from 1.1 +/- 0.2 to 2.5 +/- 0.5 mumol/min. In contrast, the natriuretic responses to saline loading in normal rats (from 1.7 +/- 0.2 to 21.6 +/- 2.4 mumol/min) and to the infusion of ANP (from 0.8 +/- 0.1 to 7.6 +/- 0.8 mumol/min) were not significantly attenuated in rats with papillary necrosis. The absence of a natriuretic response to hypervolemia in rats with papillary necrosis was not a result of failure to secrete ANP, because plasma levels of immunoreactive ANP increased three- to four-fold in rats with papillary necrosis and in untreated rats. It is concluded that the mechanisms mediating the natriuretic and diuretic responses to acute expansion of the blood volume mainly involve alterations in inner medullary function. In contrast, natriuretic responses to saline loading and pharmacological doses of ANP are apparently mediated by more superficial cortical nephrons.

Effect on blood pressure of chemically induced renomedullectomy in normotensive and spontaneously hypertensive rats.

An antihypertensive function in systemic blood pressure control has been attributed to the renal medulla. In order to examine this hypothesis normotensive and spontaneously hypertensive rats of the Münster strain (SHR) were chemically renomedullectomized by 2-bromoethylamine hydrobromide (BEA), injected intraperitoneally in a single dose of 200 mg/kg body weight. Within 5 weeks blood pressure of the BEA-treated normotensive rats and SHR rose by 17.2 +/- 15.2 and 27.7 +/- 21.0 mmHg (mean values +/- s.d; P less than 0.01), respectively, returning to baseline after 2 further weeks. Blood pressure was unchanged in the normotensive rats and SHR controls that were given isotonic saline instead of BEA solution. During maximum blood pressure in BEA-treated animals histological signs of severe renomedullary inflammation with papillary necrosis were demonstrable, while urine flow rates were elevated. Despite these disturbances renal function remained normal. These similar responses make it unlikely that a lack of a renomedullary vasodilator plays a major role in the pathogenesis of spontaneous hypertension in the Münster strain.