RESUMEN
Preeclampsia is a complication of pregnancy characterised by gestational hypertension, proteinuria and/or end organ disease. The reduced uteroplacental perfusion (RUPP) model, via partial occlusion of the lower abdominal aorta, mimics insufficient placental perfusion as a primary causal characteristic of preeclampsia. However, a major limitation of the RUPP model is that perfusion is reduced to the entire hindquarters of the rat resulting in hindlimb ischemia. We hypothesised that clipping the uterine and ovarian arteries in the selective (s)RUPP model would provoke signs of preeclampsia while avoiding systemic ischemia. Sham, RUPP or sRUPP procedures were performed in pregnant Sprague Dawley rats on gestational day (GD)14. On GD21 uterine blood flow was significantly reduced in both the RUPP and sRUPP models while aortic flow was reduced only in RUPP. Both models resulted in increased MAP, increased vascular oxidative stress (superoxide generation), increased pro-inflammatory (RANTES) and reduced pro-angiogenic (endoglin) mediators. Vascular compliance and constriction were unaltered in either RUPP or sRUPP groups. In summary, refinements to the RUPP model simultaneously maintain the characteristic phenotype of preeclampsia and avoid peripheral ischemia; providing a useful tool which may be used to increase our knowledge and bring us closer to a solution for women affected by preeclampsia.
Asunto(s)
Susceptibilidad a Enfermedades , Modelos Biológicos , Placenta/irrigación sanguínea , Placenta/metabolismo , Preeclampsia/etiología , Preeclampsia/metabolismo , Útero/irrigación sanguínea , Útero/metabolismo , Animales , Biomarcadores , Presión Sanguínea , Citocinas/sangre , Citocinas/metabolismo , Femenino , Mediadores de Inflamación , Estrés Oxidativo , Preeclampsia/diagnóstico , Preeclampsia/fisiopatología , Embarazo , Resultado del Embarazo , Proteinuria , Ratas , Flujo Sanguíneo Regional , Investigación Biomédica TraslacionalRESUMEN
Exposure to prenatal hypoxia in rats leads to intrauterine growth restriction (IUGR), decreases fetal cardiomyocyte proliferation and increases the risk to develop cardiovascular diseases (CVD) later in life. The tumor necrosis factor-related weak inducer of apoptosis (TWEAK) induces cardiomyocyte proliferation through activation of the fibroblast growth factor-inducible molecule 14 (Fn-14) receptor. The TWEAK/Fn-14 pathway becomes quiescent shortly after birth, however, it becomes upregulated with CVD; suggesting that it could be a link between the increased susceptibility to CVD in pregnancies complicated by hypoxia/IUGR. We hypothesized that offspring exposed to prenatal hypoxia will exhibit reduced cardiomyocyte proliferation due to reduced Fn-14 expression and that the TWEAK/Fn-14 pathway will be expressed in those adult offspring. We exposed pregnant Sprague Dawley rats to control (21% oxygen) or hypoxic (11% oxygen) conditions from gestational days 15 to 21. Ventricular cardiomyocytes were isolated from male and female, control and hypoxic offspring at postnatal day 1. Proliferation was assessed in the presence or absence of r-TWEAK (72 h, 100 ng/ml). Prenatal hypoxia was not associated with differences in Fn-14 protein expression in either male or female offspring. Cardiomyocytes from prenatal hypoxic male, but not female, offspring had decreased proliferation compared with controls. Addition of r-TWEAK increased cardiomyocyte proliferation in all offspring. In adult offspring of all groups, the TWEAK/Fn-14 pathway was not detectable. Cardiomyocyte proliferation was reduced in only male offspring exposed to prenatal hypoxia but this was not due to changes in the Fn-14 pathway. Studies addressing other pathways associated with CVD and prenatal hypoxia are needed.
Asunto(s)
Citocina TWEAK/metabolismo , Retardo del Crecimiento Fetal/patología , Hipoxia Fetal/patología , Miocitos Cardíacos/patología , Receptor de TWEAK/metabolismo , Factores de Edad , Animales , Animales Recién Nacidos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/patología , Enfermedades Cardiovasculares/prevención & control , Proliferación Celular , Células Cultivadas , Citocina TWEAK/sangre , Citocina TWEAK/genética , Modelos Animales de Enfermedad , Femenino , Retardo del Crecimiento Fetal/etiología , Hipoxia Fetal/metabolismo , Ventrículos Cardíacos/patología , Humanos , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Efectos Tardíos de la Exposición Prenatal/patología , Efectos Tardíos de la Exposición Prenatal/prevención & control , Cultivo Primario de Células , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Factores SexualesRESUMEN
The risk of developing cardiovascular diseases is known to begin before birth and the impact of the intrauterine environment on subsequent adult health is currently being investigated from many quarters. Following our studies demonstrating the impact of hypoxia in utero and consequent intrauterine growth restriction (IUGR) on the rat cardiovascular system, we hypothesized that changes extend throughout the vasculature and alter function of the renal artery. In addition, we hypothesized that hypoxia induces renal senescence as a potential mediator of altered vascular function. We demonstrated that IUGR females had decreased responses to the adrenergic agonist phenylephrine (PE; pEC50 6.50 ± 0.05 control v. 6.17 ± 0.09 IUGR, P < 0.05) and the endothelium-dependent vasodilator methylcholine (MCh; E max 89.8 ± 7.0% control v. 41.0 ± 6.5% IUGR, P < 0.001). In IUGR females, this was characterised by increased basal nitric oxide (NO) modulation of vasoconstriction (PE pEC50 6.17 ± 0.09 IUGR v. 6.42 ± 0.08 in the presence of the NO synthase inhibitor N-nitro-l-arginine methyl ester hydrochloride (l-NAME; P < 0.01) but decreased activated NO modulation (no change in MCh responses in the presence of l-NAME), respectively. In contrast, IUGR males had no changes in PE or MCh responses but demonstrated increased basal NO (PE pEC50 6.29 ± 0.06 IUGR v. 6.42 ± 0.12 plus l-NAME, P < 0.01) and activated NO (E max 37.8 ± 9.4% control v. -0.8 ± 13.0% plus l-NAME, P < 0.05) modulation. No significant changes were found in gross kidney morphology, proteinuria or markers of cellular senescence in either sex. In summary, renal vascular function was altered by hypoxia in utero in a sex-dependent manner but was unlikely to be mediated by premature renal senescence.
Asunto(s)
Retardo del Crecimiento Fetal/etiología , Hipoxia/complicaciones , Arteria Renal/fisiología , Animales , Colina/análogos & derivados , Colina/farmacología , Femenino , Masculino , Óxido Nítrico/sangre , Fenilefrina/farmacología , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas Sprague-DawleyRESUMEN
We have previously shown that adult rat offspring born intrauterine growth restricted (IUGR) as a result of a prenatal hypoxic insult exhibit several cardiovascular characteristics that are compatible with common manifestations of chronic iron toxicity. As hypoxia is one of the major regulators of iron absorption and metabolism, we hypothesized that hypoxia-induced IUGR offspring will have long-term changes in their ability to regulate iron metabolism leading to myocardial iron deposition and induction of myocardial oxidative stress. Pregnant Sprague Dawley rats were randomized to control (n = 8) or maternal hypoxia (11.5% oxygen; n = 8) during the last 6 days of pregnancy. At birth, litters were reduced to eight pups (four male and four female). At 4 or 12 months of age, offspring were euthanatized and samples (blood and myocardium) were collected. In only the male offspring, IUGR and aging were associated with an increase in myocardial markers of oxidative stress such as oxidized/reduced glutathione ratio and malondialdehyde. Aged male IUGR offspring also exhibited interstitial myocardial remodeling characterized by myocyte loss and disrupted extracellular matrix.Contrary to our hypothesis, however, neither IUGR nor aging were associated with changes in any systemic or local markers of iron metabolism. Our results suggest that hypoxic insults leading to IUGR produce long-term effects on the levels of oxidative stress and connective tissue distribution in the myocardium of male but not female offspring.
Asunto(s)
Retardo del Crecimiento Fetal/fisiopatología , Estrés Oxidativo , Efectos Tardíos de la Exposición Prenatal , Envejecimiento , Animales , Femenino , Glutatión/metabolismo , Hipoxia , Hierro/metabolismo , Masculino , Miocardio/metabolismo , Miocardio/patología , Embarazo , Ratas Sprague-Dawley , Factores SexualesRESUMEN
There is now a demonstrated association between low birth weight and increased mortality later in life. Changes in fetal development may program the cardiovascular system and lead to an increased risk of cardiovascular diseases later in life. In addition, aging is a risk factor for vascular endothelial-dependent dysfunction. However, the impact of being born intrauterine growth restricted (IUGR) on the normal aging mechanisms of vascular dysfunction is not clear. We hypothesized that IUGR would cause changes in vascular function that would affect the mechanisms of flow-induced vasodilation later in life in an age- or sex-dependent manner. To create an IUGR model, pregnant Sprague-Dawley rats were placed in a hypoxic (11.5% O2) or control (room air, 21% O2) environment from days 15 to 21 of pregnancy. Both male and female offspring were investigated at 4 or 12 mo of age. Vascular function was assessed in small mesenteric arteries using flow-induced vasodilation, a physiological stimuli of vasodilation, in a pressure myograph. Flow-induced vasodilation was unaffected at a young age, but was significantly reduced in aging IUGR compared with aging controls (P < 0.05). Underlying vasodilator mechanisms were altered such that nitric oxide-mediated vasodilation was abolished in both young adult and aging IUGR males and females and in aging control females (P > 0.05). Endothelium-derived hyperpolarizing factor-mediated vasodilation was maintained in all groups (P < 0.01). A change in the mechanisms of vasodilation occurring at an earlier age in IUGR offspring may predispose them to develop cardiovascular diseases as an aging adult.
Asunto(s)
Retardo del Crecimiento Fetal/fisiopatología , Hipoxia/fisiopatología , Arterias Mesentéricas/fisiopatología , Efectos Tardíos de la Exposición Prenatal , Vasodilatación/fisiología , Envejecimiento/fisiología , Animales , Presión Sanguínea/fisiología , Modelos Animales de Enfermedad , Endotelio Vascular/fisiopatología , Femenino , Masculino , Embarazo , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/fisiología , Factores SexualesRESUMEN
Numerous epidemiological studies have shown that cardiovascular dysfunction in adult life may be programmed by compromised growth in utero. Aging is a risk factor for vascular endothelial-dependent dysfunction. After birth, the impact of intrauterine growth restriction (IUGR) on normal aging mechanisms of vascular dysfunction is not known. We hypothesized that IUGR would cause changes in vascular function that would affect the mechanisms of endothelium-dependent vasodilation later in life in an age- or sex-dependent manner. To create an IUGR model, pregnant Sprague-Dawley rats were placed in a hypoxic (12% O(2)) or control (room air, 21% O(2)) environment from days 15 to 21 of the pregnancy, and both male and female offspring were investigated at 4 or 12 mo of age. Endothelial function was assessed in small mesenteric arteries using methacholine (MCh)-induced vasodilation in a wire myograph system. The involvement of nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor (EDHF) was assessed using the inhibitors N(omega)-nitro-l-arginine methyl ester hydrochloride, meclofenamate, or a combination of apamin and TRAM-34 (SK(Ca) and IK(Ca) blockers), respectively. EDHF-induced vasodilation was further investigated by using inhibitors of P450 epoxygenases [N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide] and gap junctions (18alpha-glycyrrhetinic acid). NO-mediated vasodilation was significantly reduced in aged controls and both young and aged IUGR females. EDHF-mediated vasodilation was maintained in all groups; however, an additional involvement of gap junctions was found in females exposed to hypoxia in utero, which may represent a compensatory mechanism. A change in the mechanisms of vasodilation occurring at an earlier age in IUGR offspring may predispose them to adult cardiovascular diseases.
Asunto(s)
Envejecimiento/fisiología , Preñez , Vasodilatación/fisiología , Animales , Arterias/fisiopatología , Factores Biológicos/farmacología , Peso Corporal , Femenino , Retardo del Crecimiento Fetal , Humanos , Hipoxia/embriología , Hipoxia/fisiopatología , Masculino , Arterias Mesentéricas/efectos de los fármacos , Arterias Mesentéricas/fisiología , NG-Nitroarginina Metil Éster/farmacología , Embarazo , Complicaciones del Embarazo/fisiopatología , Preñez/fisiología , Ratas , Ratas Sprague-Dawley , Valores de Referencia , VasoconstricciónRESUMEN
BACKGROUND AND PURPOSE: Hypothalamic neuropeptides centrally modulate sexual arousal. However, the role of neuropeptides in peripheral arousal has been ignored. Vascular and non-vascular smooth muscle relaxation in the vagina is important for female sexual arousal. To date, in vitro studies have focused on vaginal strips with no studies on vaginal arteries. The aim of this study was to compare the effects of sexual hypothalamic neuropeptides on rabbit vaginal wall strips and arteries. EXPERIMENTAL APPROACH: Tissue bath and wire myography techniques were used to measure isometric tension from strips and arteries, respectively. KEY RESULTS: Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) relaxed both preparations, effects that were only antagonized by the VIP/PACAP antagonist VIP6-28 (10 nM) and the PAC(1) antagonist PACAP 6-38 (1 microM). The melanocortin agonist alpha-melanocortin-stimulating hormone (1 microM), but not bremelanotide (1 microM), also relaxed both preparations. Oxytocin and vasopressin contracted vaginal preparations, which could be antagonized by the V(1A) antagonist SR 49059. Neuropeptide Y (NPY) and the NPY Y(1) agonist Leu(31), Pro(34) NPY only contracted arteries, which was antagonized by the NPY Y(1) receptor antagonist BIBP 3226. Melanin-concentrating hormone (MCH; 1 microM) contracted arteries. CONCLUSION AND IMPLICATIONS: Hypothalamic neuropeptides can exert contractile and relaxant effects on vaginal strips and arteries. NPY Y(1), V(1A), MCH(1) antagonists as well as VIP/PAC(1) agonists may have therapeutic potential in both central and peripheral female sexual arousal. Differences in effect of neuropeptides between preparations raise the question of which preparation is important for female sexual arousal.
Asunto(s)
Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Neuropéptidos/farmacología , Vagina/anatomía & histología , Animales , Femenino , Modelos Moleculares , Relajación Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Músculo Liso Vascular/fisiología , Neuropéptido Y/farmacología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Conformación Proteica , Conejos , Péptido Intestinal Vasoactivo/farmacologíaRESUMEN
PURPOSE: In nongenital arteries a sex difference has been postulated in the dominant endothelium-derived relaxant factor(s), eg nitric oxide, prostacyclin or endothelial-derived hyperpolarizing factor. Knowledge of endothelium-derived relaxant factor mechanisms in genital tissues could influence the development of novel treatments for sexual dysfunction. We compared nitric oxide and endothelial-derived hyperpolarizing factor contributions to acetylcholine induced relaxation in the genital arteries of the 2 sexes. MATERIALS AND METHODS: Male dorsal and cavernous penile arteries, and female extravaginal and intravaginal arteries from New Zealand White rabbits were studied. Acetylcholine concentration-vasodilator response curves were constructed in the presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester, K(+) channel blockers (apamin and charybdotoxin) or a combination. Indomethacin was present throughout to exclude prostacyclins. RESULTS: Extravaginal artery relaxation was predominantly endothelial-derived hyperpolarizing factor induced. Apamin plus charybdotoxin decreased maximal relaxations from a mean +/- SEM of 77% +/- 4% to 23% +/- 3% in 6 preparations (p <0.01). However, nitric oxide and endothelial-derived hyperpolarizing factor contributed to overall function. Dorsal artery relaxation was largely nitric oxide induced. Nomega-nitro-L-arginine methyl ester decreased maximal relaxations from 90% +/- 3% to 41% +/- 9% (p <0.001) with no endothelial-derived hyperpolarizing factor involvement (p >0.05). In cavernous and intravaginal arteries nitric oxide and endothelial-derived hyperpolarizing factor contributed to acetylcholine induced relaxation, while nitric oxide predominated. Blocking nitric oxide synthase or K(+) channels indicated that myogenic tone and constitutive activity of endothelium-derived relaxant factors were present. Vasodilator nerve mediated responses were influenced by each with the former more effective. CONCLUSIONS: Vaginal inflow arteries showed a dominance of endothelial-derived hyperpolarizing factor, contrasting with nitric oxide in penile arteries. Penile arteries followed the trend that endothelial-derived hyperpolarizing factor involvement increased with decreasing vessel caliber, while the reverse was demonstrated in female arteries.
Asunto(s)
Factores Biológicos/fisiología , Endotelio Vascular/fisiología , Óxido Nítrico/fisiología , Pene/irrigación sanguínea , Pene/fisiología , Vagina/irrigación sanguínea , Vagina/fisiología , Animales , Femenino , Masculino , Relajación Muscular , Conejos , Caracteres Sexuales , Resistencia VascularRESUMEN
BACKGROUND AND PURPOSE: Maintained penile erection depends on the absence of alpha-adrenoceptor (alpha-AR) activation and so can be facilitated by alpha-blockers. This study seeks the alpha(1)-AR subtypes involved in order to inform the pro-erectile consequences of subtype selective blockade. EXPERIMENTAL APPROACH: Wire myography was used with dorsal (nutritional supply) and cavernous (erectile inflow) penile arteries; standard alpha-AR-selective agonists and antagonists were employed to classify responses. KEY RESULTS: In both penile arteries noradrenaline (NA) and phenylephrine (PE, alpha(1)-AR agonist) caused concentration-dependent contractions. Sensitivity to NA was increased by NA uptake blockers, cocaine (3 microM) and corticosterone (30 microM). PE responses were antagonised by phentolamine (non-selective alpha-AR: dorsal pK(B) 8.00, cavernous 8.33), prazosin (non-subtype-selective alpha(1)-AR: dorsal 8.60, cavernous 8.41) and RS100329 (alpha(1A)-AR selective: dorsal 9.03, cavernous 8.80) but not by BMY7378 (alpha(1D)-AR selective: no effect at 1-100 nM) or Rec15/2615 (alpha(1B)-AR selective: no effect at 1-100 nM). Schild analysis was straightforward in cavernous artery, indicating that PE activates only alpha(1A)-AR. In dorsal artery Schild slopes were low, though alpha(1A)-AR was still indicated. Analysis using UK 14,304 and rauwolscine indicated an alpha(2)-AR component in dorsal artery that may account for low slopes to alpha(1)-AR antagonists. CONCLUSIONS AND IMPLICATIONS: Penile arteries have a predominant, functional alpha(1A)-AR population with little evidence of other alpha(1)-AR subtypes. Dorsal arteries (nutritional supply) also have alpha(2)-ARs. Thus, alpha-AR blockers with affinity for alpha(1A)-AR or alpha(2)-AR would potentially have pro-erectile properties; the combination of these perhaps being most effective. This should inform the design of drugs to assist/avoid penile erection.
Asunto(s)
Arterias/efectos de los fármacos , Pene/irrigación sanguínea , Receptores Adrenérgicos alfa 1/fisiología , Agonistas alfa-Adrenérgicos/farmacología , Animales , Arterias/fisiología , Masculino , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Fenilefrina , ConejosRESUMEN
BACKGROUND: There is a considerable body of literature which indicates that contrast thresholds for the detection of sinusoidal grating patterns are abnormally high in glaucoma, though just how these elevations are related to the location of visual field loss remains unknown. Our aim, therefore, has been to determine the relationship between contrast threshold elevation and visual field loss in corresponding regions of the peripheral visual field in glaucoma patients. METHODS: Contrast thresholds were measured in arcuate regions of the superior, inferior, nasal and temporal visual field in response to laser interference fringes presented in the Maxwellian view. The display consisted of vertical green stationary laser interference fringes of spatial frequency 1.0 c deg(-1) which appeared in a rotatable viewing area in the form of a truncated quadrant extending from 10 to 20 degrees from fixation which was marked with a central fixation light. Results were obtained from 36 normal control subjects in order to provide a normal reference for 21 glaucoma patients and 5 OHT (ocular hypertensive) patients for whom full clinical data, including Friedmann visual fields, had been obtained. RESULTS: Abnormally high contrast thresholds were identified in 20 out of 21 glaucoma patients and in 2 out of 5 OHT patients when compared with the 95% upper prediction limit for normal values from one eye of the 36 normal age-matched control subjects. Additionally, inter-ocular differences in contrast threshold were also abnormally high in 18 out of 20 glaucoma patients who had vision in both eyes compared with the 95% upper prediction limit. Correspondence between abnormally high contrast thresholds and visual field loss in the truncated quadrants was significant in 5 patients, borderline in 4 patients and absent in 9 patients. CONCLUSION: While the glaucoma patients tested in our study invariably had abnormally high contrast thresholds in one or more of the truncated quadrants in at least one eye, reasonable correspondence with the location of the visual field loss only occurred in half the patients studied. Hence, while contrast threshold elevations are indicative of glaucomatous damage to vision, they are providing a different assessment of visual function from conventional visual field tests.
Asunto(s)
Sensibilidad de Contraste/fisiología , Glaucoma de Ángulo Abierto/fisiopatología , Trastornos de la Visión/fisiopatología , Campos Visuales/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Humanos , Interferometría , Presión Intraocular , Rayos Láser , Persona de Mediana Edad , Hipertensión Ocular/fisiopatología , Sensibilidad y Especificidad , Umbral Sensorial/fisiologíaRESUMEN
AIMS: Previously, we demonstrated that gastrin peptides as long as 34 amino acids were absorbed from the ileum of rat after conjugation to the C24 position of cholic acid and that these peptides retained full biological activity. As absorption was specific to the ileum, it was inferred that the conjugated hormone was taken up by the bile salt transporters. We have now extended these experiments to a member of a different family of hormones, viz. secretin, a 27-amino acid hormone that stimulates serous secretions from the exocrine pancreas. METHODS: After conjugation to cholic acid, the degree of cholylsecretin absorption from the ileum of anaesthetized rats was assessed from the increase in pancreatic secretions. RESULTS: A complication to the study was that intra-ileal infusion of native secretin caused a transient increase in the levels of pancreatic secretions. This was in contrast to the effects of intra-ileal infusion of cholylsecretin which did not cause this transient increase but, instead, gave rise to a delayed increase in pancreatic secretions which was sustained over several hours during which cholylsecretin was detected in plasma in high concentration by mass spectrometry. The pancreatic response to cholylsecretin was abolished by co-infusion of 50 mm taurocholate, employed to compete with the bile salt transporters, although a transient increase in pancreatic secretions similar to that caused by secretin was now generated. This was shown to arise from an action of taurocholate per se causing the release of endogenous secretin which is present in rat ileum. CONCLUSIONS: We, therefore, concluded that cholylsecretin had been absorbed from the rat ileum by uptake by bile salt transporters.
Asunto(s)
Ácido Cólico/química , Íleon/metabolismo , Secretina/farmacocinética , Absorción , Animales , Presión Sanguínea , Colagogos y Coleréticos/farmacología , Íleon/anatomía & histología , Infusiones Parenterales , Inyecciones Intravenosas , Mucosa Intestinal/anatomía & histología , Mucosa Intestinal/metabolismo , Masculino , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Ratas , Ratas Wistar , Secretina/administración & dosificación , Secretina/química , Ácido Taurocólico/administración & dosificaciónRESUMEN
Thyroids from mule deer (Odocoileus hemionus) were collected in New Mexico, Colorado, Wyoming and Idaho and 129I/127I atom ratios were determined. Iodine-129/127 atom ratios were significantly (P less than 0.005) different among states. Ratios in Wyoming and Idaho control thyroids were significantly (P less than 0.05) larger than ratios in New Mexico and Colorado. Fallout from past atmospheric nuclear tests at the Nevada Test Site is suggested as a possible explanation for the differences in ratios. Average 129I/127I ratios in thyroids of other large mammals collected 54 km west and 116 km northeast of the Idaho National Engineering Laboratory (INEL) in south eastern Idaho were up to 15 times those found in control thyroid samples from Idaho. Atmospheric effluents from the Idaho Chemical Processing Plant located on the INEL were likely responsible for the increased ratios in animals collected in the INEL vicinity. Although of no health consequence to the animals, 129I in deer thyroids may be a sensitive indicator of contaminants from nuclear fuel reprocessing plants and atmospheric nuclear tests or accidents.