Treatment of open-angle glaucoma and ocular hypertension with preservative-free tafluprost/timolol fixed-dose combination therapy: 6 case reports and clinical outcomes.

BACKGROUND: Treatment of open angle glaucoma (OAG) and/or ocular hypertension (OHT) focuses on achievement of target intraocular pressure (IOP), with the objective of slowing disease progression. However, ocular surface health is an important consideration in the optimization of treatment. We report 6 patient cases in which enhanced IOP control was achieved following appropriate management of ocular surface inflammation and a therapeutic switch to the preservative-free (PF) tafluprost (0.0015%)/timolol (0.5%) fixed-dose combination (FC). CASE PRESENTATION: Six patient cases, aged 48-74 years, presented with OAG or OHT. Each patient had signs and symptoms of ocular surface disease (OSD). Cases 1-3 were each receiving maximal medical therapy for OAG; regimens comprising prostaglandin analogue (PGA), ß-blocker, carbonic anhydrase inhibitor (CAI) and α-2 agonist agents (including treatments containing preservative agent). Cases 1 and 2 reported IOP values ≥23 mmHg in each eye, and wide IOP fluctuations were identified when reviewing patient data concerning case 3 (11-20 mmHg). Maximal therapy was ceased and PF tafluprost/timolol FC was initiated, after which the signs and symptoms of OSD were improved and IOP was reduced (≤18 mmHg for cases 1-3) and stabilized. Cases 4 and 5 were diagnosed with OAG and case 6 had OHT. Each had symptoms and signs of OSD and were treated with a preserved PGA monotherapy (latanoprost 0.005% or bimatoprost 0.03%). At presentation, IOP was 24 mmHg in both eyes (case 4), ≥18 mmHg (case 5) and ≥ 22 mmHg (case 6). Following a switch to the PF tafluprost/timolol FC, OSD symptoms were improved and IOP was 14 mmHg (both eyes; case 4), ≤14 mmHg (case 5) and 16 mmHg (both eyes; case 6). CONCLUSIONS: In addition to IOP-lowering efficacy, approaches to the management of OAG and OHT should consider the impact of treatment tolerability and the susceptibility of these patients to OSD. The presence of ocular surface inflammation appears to be detrimental to adherence and therefore to the effectiveness of topical medications. Addressing OSD through the use of PF FC formations, such as the PF tafluprost/timolol FC, reduces exposure to potentially toxic agents and facilitates improvements in IOP control.

Plasticity of haemoglobin concentration and thermoregulation in a mountain lizard.

The plastic capability of species to cope with the new conditions created by climate change is poorly understood. This is particularly relevant for organisms restricted to high elevations because they are adapted to cold temperatures and low oxygen availability. Therefore, evaluating trait plasticity of mountain specialists is fundamental to understand their vulnerability to environmental change. We transplanted mountain lizards, Iberolacerta cyreni, 800 m downhill to evaluate the plastic response in body condition, thermoregulation traits, haemoglobin level, and haemoparasite load. Initial measurements of body mass, total haemoglobin concentration ([Hb]), hematic parasite intensities, dorsal luminance, and thermoregulatory behaviour were resampled after two and four weeks of acclimation. We also tested whether an anti-parasitic drug reduced haemoparasite intensity. After only two weeks of acclimation to a lower elevation, lizards decreased 42% in [Hb], had 17% less parasite intensities, increased body condition by 25%, and raised by ~3% their mean preferred temperatures and their voluntary thermal maximum. The anti-parasitic treatment had no significant effect on the intensity of hematic parasites, but our results suggest that negative effects of haemoparasites on [Hb] are relaxed at lower elevation. The rapid plastic changes observed in thermal preferences, body condition, [Hb], and parasite intensity of I. cyreni demonstrate a potential plastic response of a mountain specialist. This may be adaptive under the climatic extremes typical of mountain habitats. However, there is uncertainty in whether the observed plasticity can also help overcome long term environmental changes.

Twenty-four-hour intraocular pressure and ocular perfusion pressure characteristics in newly diagnosed patients with normal tension glaucoma.

PurposeTo determine the mean 24-h intraocular pressure (IOP) and mean ocular perfusion pressure (MOPP) characteristics of newly diagnosed, previously untreated, Caucasian, normal tension glaucoma (NTG) patients and to identify relationships between these features and visual field (VF) loss at diagnosis.MethodsConsecutive newly diagnosed NTG patients underwent 24-h habitual IOP and blood pressure (BP) monitoring. Parameters from pooled measurements obtained in the sitting (0800-2200 hours) and supine (1200-0600 hours) positions were compared and associations were sought with VF mean deviation (MD) and pattern standard deviation (PSD).ResultsSixty-two Caucasian NTG patients (24 men and 38 women) successfully completed circadian IOP and BP monitoring. In habitual position, 8 subjects (12.9%) exhibited a diurnal acrophase, 42 subjects (67.7%) demonstrated a nocturnal acrophase, one subject (1.6%) showed a flat rhythm and 11 patients (17.7%) revealed a biphasic/polyphasic rhythm. Nighttime MOPP values (supine position) were significantly greater than diurnal values (sitting position); (P<0.001). No association could be demonstrated between glaucomatous damage, as indicated by VF parameters, and either mean habitual 24-h IOP (P=0.20 and P=0.12 for MD and PSD, respectively), or habitual 24-h MOPP (P=0.96 and 0.29, for MD and PSD, respectively).ConclusionsIn this cohort of Caucasian NTG patients, most patients exhibited a nocturnal IOP acrophase when evaluated in a habitual position. No association was found between 24-h IOP or MOPP and VF damage.

Twenty-four hour efficacy with the dorzolamide/timolol-fixed combination compared with the brimonidine/timolol-fixed combination in primary open-angle glaucoma.

AIM: The aim of this study is to compare the 24-hour efficacy of dorzolamide/timolol-fixed combination (DTFC) and brimonidine/timolol-fixed combination (BTFC) in primary open-angle glaucoma (POAG). METHODS: One eye each of 77 POAG patients was included in this prospective, observer-masked, crossover comparison. Following a 2-month timolol run-in period, patients had three intraocular pressure (IOP) measurements at 1000, 1200 and 1400 h while on timolol treatment. Patients showing at least a 20% IOP reduction on timolol were randomised to 3 months of therapy with DTFC or BTFC, and then were crossed over to the opposite therapy. RESULTS: Sixty POAG patients completed the study. The mean 24-hour IOP was significantly reduced with both the fixed combinations compared with the timolol-treated diurnal IOP (P < 0.001). When the two fixed combinations were compared directly, DTFC demonstrated a lower mean 24-hour IOP level as compared with BTFC (mean difference: -0.7 mm Hg, 95% confidence interval (CI): (-1.0, -0.3), P < 0.001). At two individual time points, DTFC significantly reduced IOP more than BTFC: at 1800 h (-1.0 mm Hg, 95% CI (-1.6,-0.5), P = 0.001) and at 0200 (-0.9 mm Hg, 95% CI: (-1.4,-0.5), P = 0.001). No significant difference existed for the other time points. CONCLUSION: Both the fixed combinations significantly reduce 24-hour IOP in POAG. DTFC provided significantly better 24-hour efficacy.

Correlates of species richness in the largest Neotropical amphibian radiation.

Although tropical environments are often considered biodiversity hotspots, it is precisely in such environments where least is known about the factors that drive species richness. Here, we use phylogenetic comparative analyses to study correlates of species richness for the largest Neotropical amphibian radiation: New World direct-developing frogs. Clade-age and species richness were nonsignificantly, negatively correlated, suggesting that clade age alone does not explain among-clade variation in species richness. A combination of ecological and morphological traits explained 65% of the variance in species richness. A more vascularized ventral skin, the ability to colonize high-altitude ranges, encompassing a large variety of vegetation types, correlated significantly with species richness, whereas larger body size was marginally correlated with species richness. Hence, whereas high-altitude ranges play a role in shaping clade diversity in the Neotropics, intrinsic factors, such as skin structures and possibly body size, might ultimately determine which clades are more speciose than others.

Twenty-four-hour intraocular pressure and blood pressure levels with bimatoprost versus latanoprost in patients with normal-tension glaucoma.

AIM: To evaluate 24 h intraocular pressure (IOP) and blood pressure (BP) with bimatoprost or latanoprost in patients with normal-tension glaucoma. DESIGN: Prospective, randomised, crossover, active-controlled, observer-masked study. METHODS: After a 6-week medicine-free period, we randomised patients to either latanoprost or bimatoprost for 8 weeks and then to the opposite medicine for 8 weeks. At baseline, and at the end of each treatment period, we evaluated IOP and BP at 08:00 and then every 2 h over the 24 h day. Diastolic ocular perfusion pressure (DOPP) was calculated from the above parameters. RESULTS: Forty completed patients had a 24 h untreated baseline IOP of 15.5 (2.3) mm Hg, and a DOPP of 59.2 (6.1) mm Hg. Both treatments lowered IOP at each time point (p<0.006), and over the 24 h curve (p<0.001, both medicines 13.1 mm Hg, 16% decrease). No difference existed between treatments in absolute IOP, at each time point, and over the 24 h curve (p>or=0.26). Additionally, no differences were found between treated 24 h systolic (p>or=0.29) and diastolic BP (p>or=0.12). The mean 24 h DOPP for latanoprost was increased from baseline (3%, p = 0.031) but not for bimatoprost (2%, p = 0.21). However, no difference in DOPP existed between treatments at any time point or over the 24 h curve (p>or=0.17). No difference was observed between treatments for any adverse event (p>0.05). CONCLUSIONS: In patients with normal-tension glaucoma, both bimatoprost and latanoprost reduce the 24 h intraocular pressure from untreated baseline to a similar extent. Latanoprost is associated with slightly improved ocular diastolic perfusion pressure over 24 h but similar absolute perfusion levels to that of bimatoprost.

Impaired response to insulin associated with protein kinase C in chronic fructose-induced hypertension.

A fructose-enriched diet induces an increase in blood pressure associated with metabolic alterations in rats. Our hypothesis was that an increase in protein kinase C (PKC) activation, reported in the acute period of fructose overload, and an impaired vessel's response to vasoactive substances contribute to maintain elevated blood pressure levels in the chronic period. The aims of this study were to investigate in this animal model of hypertension: (1) if the increase in PKC activation was also found in the chronic stage; (2) the involvement of nitric oxide and insulin in the vessel's response; and plasma atrial natriuretic factor and nitrites/nitrates (nitric oxide metabolites) behavior. We evaluated the effects of: PKC-stimulator 12,13-phorbol dibutyrate, phenylephrine, insulin, nitric oxide synthase-inhibitor NG-nitro-L-arginine methyl esther (L-NAME) and PKC-inhibitor Calphostin C on aortic rings responses of Sprague-Dawley rats: fructose-fed and control. The fructose-fed group showed higher contractility to 12,13-phorbol dibutyrate than the control group in aortic rings pre-incubated with insulin, and this difference disappeared with L-NAME. The response to phenylephrine in rings pre-incubated with Calphostin C was decreased in the fructose-fed group and increased with Calphostin C plus L-NAME. Fructose-fed rats showed higher levels of plasma atrial natriuretic factor and nitrites/nitrates than controls. In conclusion, chronic fructose feeding seems to develop an impaired response to insulin, dependent on nitric oxide, suggesting a PKC alteration. Vasorelaxant agents, such as atrial natriuretic factor and nitric oxide, would behave as compensatory mechanisms in response to high blood pressure.

Serotonin hypersensitivity in aorta of two kidney-two clip hypertensive rats: calcium contribution and prostanoids-nitric oxide interactions.

Previous studies from our own laboratory have shown that abdominal aorta rings from two kidney - two clip hypertensive rats (HT) develop hypersensitivity to serotonin (SER) which is related to a decreased nitric oxide (NO) availability and enhanced thromboxane A2 production. In the present study we investigated whether calcium and prostanoid-NO interactions are involved in these findings. To this purpose, the aortic responses to SER were analyzed in calcium-free medium and in calcium-depleted aorta placed in normal medium. Moreover, effects of ridogrel (RID, an antagonist of TxA 2/PGH2 receptors and inhibitor of thromboxane synthetase) were analysed by cumulative dose-response curves to SER in the presence and in the absence of the NO synthase inhibitor N(omega)-nitro-L-arginine (NOLA). Vascular responses to SER in vessels from HT rats were associated with increased intracellular calcium mobilization. In addition, hypersensitivity to SER in HT group respect to sham group (SH) disappeared in the presence of RID, NOLA and RID plus NOLA. RID decreases the maximum tension to SER and this effect was prevented by NOLA. This inhibition was of a greater magnitude in rings from sham rats (SH): 34 +/- 6% than in HT rats: 15 +/- 6% (p < 0.05). Besides, RID decreased the sensibility to SER in the presence of NOLA only in the HT group. In conclusion, the present study suggests that SER hypersensitivity observed in HT rats is related to a facilitated intracellular calcium mobilization and enhanced TxA2-endoperoxide response. Changes in membrane SER-gated calcium channels opening are observed only during the early hypertensive period. Besides, the lower depressor effect of RID on the maximal tension to SER in aorta rings from HT rats are related with a decreased NO availability in this model of renovascular hypertension.

[Retrospective study of early readmissions at an internal medicine service]. / Estudio retrospectivo de los reingresos precoces de un servicio de medicina interna.

OBJECTIVE: To determine the frequency of hospital re-admissions to an Internal Medicine Department at a Community General Hospital as well as variables associated with them. METHODS: Analysis of hospital discharges during 1997. Data were provided by the Coding and Filing Service, and included sociodemographic data and aspects related to medical care to each patient, as well as discharge DRF according to the HCFA version. A logistic regression model was developed to identify variables independently associated with early re-admission risk (less than 30 days after discharge). RESULTS: The rate of early re-admission was 7.4%. The variables associated with a higher risk of admission included age, a hospital stay longer than the mean at first admission, and AIDS-associated conditions and heart diseases as main discharge diagnoses. CONCLUSIONS: Based on our data, we cannot consider the readmission rates as a reliable index in itself to be assessed negatively, as some re-admissions come unexpectedly and/or are unavoidable.

Estudio retrospectivo de los reingresos precoces de un servicio de medicina interna / Retrospective study of early readmissions to an Internal Medicine Department

Objetivo. Determinar la frecuencia del reingreso hospitalario en un servicio de Medicina Interna de un Hospital General de la Comunidad, así como las variables asociadas al mismo. Métodos. Análisis de las altas durante el año 1997. Los datos fueron facilitados por el Servicio de Codificación y Archivo, incluyendo características sociodemográficas y aspectos relacionados con el proceso asistencial de cada paciente, así como sus GRD al alta según la versión HCFA. Se construyó un modelo de regresión logística para identificar las variables que se asocian independientemente con el riesgo de reingresar precozmente (menos de 30 días tras el alta). Resultados. La tasa de reingresos precoces es del 7,4 por ciento. Las variables asociadas a un mayor riesgo de reingreso fueron la edad, una estancia superior a la media en el primer ingreso, así como la patología asociada con el síndrome de inmunodeficiencia adquirida (SIDA) y la cardiopatía como diagnósticos principales al alta. Conclusiones. Con los datos obtenidos no podemos considerar la tasa de reingresos como un índice fiable de calidad en sí mismo que deba ser valorado negativamente, ya que algunos reingresos son inesperados y/o inevitables. (AU)

Effect of oral L-arginine administration for three weeks in two kidney-two clip hypertensive rats.

Nitric oxide (NO) has been identified as an effective vascular relaxant. This study analyses the contribution of the precursor L-arginine (L-arg) by oral administration in two kidney-two clip hypertension in the rat (2K-2C). Two groups were studied: sham (SH, n=21) and hypertensive (HT, n=15). After 4 weeks of surgery, a group of rats remained as controls (SHc and HTc, respectively), while others were supplemented with L-arg (1.25 g/L) in drinking water (SHa and HTa) for 3 weeks. Blood pressure was significantly increased in 2K-2C rats but remained unchanged after L-arg treatment. Plasma nitrite/nitrate concentrations were not different among groups. The contractile response of aorta to KCl, serotonin and the protein kinase C (PKC) stimulant, phorbol 12,13-dibutyrate (PDBu) was also evaluated. Higher contractile responses to PDBu (p<0.001) and lower relaxation to acetylcholine (Ach 10(-6) M, p<0.05 and 10(-5)M, p<0.02) were observed in aortic rings of HTc vs SHc; L-arg supplementation significantly diminished tension development to all agonists (p<0.05) but failed to modify the lower relaxation to Ach in HTa. Thromboxane (TxA(2)) - synthesis in rings of HTc was higher than in SHc under basal conditions (p<0.05). In the groups with supplement of L-arg, PDBu significantly stimulated prostacyclin (PGI(2)) synthesis more in HTa rats than in SHa ones (p<0.05). To conclude: 1) L-arg fails to modify hypertension development in 2K-2C rats; and 2) L-arg exerts a beneficial effect on the vascular wall, by reducing contractility in rings from HTa rats; it also improved PGI(2) synthesis under PDBu stimulation. 3) greater PKC activation and TxA(2) production rather than lower NO availability might result in systemic hypertension in 2K-2C rats.

Potential role of glycerol leading to rat fructose hypertension.

A fructose-enriched diet promotes hypertension in rats. We thought that an enhancement of the glycolytic and/or lipid disorder (s) that raise blood pressure could be the cause. Therefore, we studied 4 groups of Sprague-Dawley rats (+/-200 g): (1) control rats received a standard diet and tap water; (2) the glycerol group of rats received a standard diet and 0.54 mol/L glycerol in tap water; (3) the fructose group was given a fructose-enhanced diet (chow had 55% fructose instead of dextrin) and tap water; and (4) the fructose-glycerol group was given the fructose-enhanced diet and 0. 54 mol/L glycerol in drinking water. At the end of the second week, the findings were as follows. Blood pressure was 149+/-2 mm Hg in the fructose-glycerol group versus 129+/-2 (P<0.001), 131+/-2 (P<0. 001), and 140+/-3 (P<0.005) mm Hg in the control, glycerol, and fructose groups, respectively. Insulinemia was higher in the fructose-glycerol group than the control (P<0.001), glycerol (P<0. 001), and fructose groups (P<0.001); triglyceridemia was higher in the fructose-glycerol (P<0.02), fructose (P<0.05), and glycerol groups (P<0.02) than the control group. Thoracic aorta rings showed a lower ED(50) to 12,13-phorbol dibutyrate in the fructose-glycerol group than in the control (P<0.001), glycerol (P<0.002), and fructose groups (P<0.001). In conclusion, glycerol-fructose administration resulted in hypertriglyceridemia, hyperinsulinemia, and increased vascular sensitivity to 12,13-phorbol dibutyrate (with respect to the control group), and significantly greater expression of protein kinase C alpha and betaII (with respect to the glycerol group).

Atrial natriuretic factor in two kidney--two clip renovascular hypertension in the rat.

Hig levels of circulating atrial natriuretic factor (ANF) have been reported in several physiopathologic conditions like hypertension, heart and renal failure, pregnancy and high sodium intake. Nevertheless, neither relationships with water-sodium space regulation nor the role of an ANF vascular relaxant effect have been yet defined. The aim of present experiments was to characterize the contribution of circulating ANF and its vascular relaxing effects in the two kidney-two clip (2K2C) experimental model of renovascular hypertension. Complementary, plasma metabolites nitrite/nitrate of nitric oxide (NO) was examined because of mediation for both (NO an ANF) through cGMP. Three results showed (two-four weeks after surgery): indirect systolic blood pressure (mmHg), 186 +/- 4 in HT and 122 +/- 1 in SH (p < 0.001); a significant increase of plasma ANF (fmol/ml) in HT (n = 7, 1221 +/- 253) vs. SH (n = 9, 476 +/- 82; p < 0.02). Nitrate/nitrite plasma concentrations (mumol/l) were mpt different between SH and. The relaxant effect of ANF (10(-9), 10(-8) and 10(-7) M) on phenylephrine (3,5 x 10(-6) M) contracted rings from HT rats was smaller than SH rats (10(-8) M, p < 0.05). Contractions to phorbol 12, 13-dibutyrate (seven weeks after surgery) were significantly higher in rings from HT rats (p < 0.001). We conclude: 1) in addition to decreased granularity in atrial myocardiocytes, high circulating values of ANF here described suggest an increased turnover of the peptide in 2K2C hypertensive rats; 2) lower significant vascular relaxant effects in HT rats would indicate down regulation of ANF receptors in this model; the latter would derive from high plasma ANF concentration and, tentatively, because of greater activity of protein kinase C in the vascular wall; 39 similar values of plasma nitrite/nitrate in SH and HT rats would indicate a comparable NO circulating availability in both groups.

Nitric oxide and superoxide anions in vascular reactivity of renovascular hypertensive rats.

The present study intends to define the role of the endothelium derived relaxing factor nitric-oxide (EDRF-NO) and the reactive oxygen intermediates in hypersensitivity to 5-hydroxytryptamine (5-HT) observed in abdominal aorta rings of two kidney-two clip hypertensive rats. Methylene Blue (which blocks production of cGMP by EDRF-NO) and Nw-nitro-L-arginine (which inhibits EDRF-NO synthesis), both shifted 5-HT dose-response curves to the left and completely abolished the differences in sensitivity to the agonist. The aortic perfusion with Krebs-Alcohol 20% (v/v) suppressed vascular relaxation to Ach (10(-5) M) and also abolished differences in sensitivity to 5-HT. These results suggest that a lower availability of EDRF-NO accounts for a higher 5-HT sensitivity in vessels of hypertensive rats. On the contrary, ridogrel (inhibitor of tromboxane-synthase and blocker of PGH2 and TxA2 receptors) did not suppress the hypersensitivity to 5-HT. In addition, since the superoxide anion (O2-) inactivates EDRF-NO, the effects of Superoxide dismutase (SOD) and Catalase (CAT) added in the bath were analyzed. Significant changes in sensitivity (P < 0.005) were found only for vessels of hypertensive rats (SOD depressing and CAT increasing sensitivity to 5-HT). Complementary, SOD activity was evaluated in the aorta homogenates and was found to be significantly lower in the hypertensive rats [(differences between hypertensive and sham rats, mU.mg wet weight tissue-1: 7 days after clipping, -183 +/- 67 (n = 11), P < 0.02; 21 days, -160 +/- 70 (n = 9), p < 0.05]. Results would indicate: 1. Lower EDRF-NO availability in vessels of the hypertensive animals which would account for higher sensitivity to 5-HT; 2. Such a lower EDRF-NO might depend, in part, upon its greater inactivation by O2- anions; 3. A greater presence of O2- anions in the vessels of hipertensive rats that might be favored by the lower SOD activity concentration in the vascular wall.

Calculation and number processing: assessment battery; role of demographic factors.

This paper describes the structure and contents of EC301, a standardized testing battery for the evaluation of brain-damaged adults in the area of calculation and number processing. The battery was administered to 180 normal subjects stratified by education (3 levels), age (3) and gender. EC301 is composed of a large variety of tasks dealing with basic arithmetic skills, and their linguistic, spatial, and mnesic dimensions. The three main notational systems for numbers--Arabic digits, written verbal, and spoken verbal number forms--are explored. Analysis of error rates indicated the effect of some demographic factors (principally, education; incidentally, gender) on normal performance in some tasks.

Ultrastructural study of atrial specific granules in experimental renovascular hypertension elicited by the constriction of both renal arteries.

The heart has an endocrine activity which depends on the secretion of a natriuretic, diuretic and hypotensive factor contained in osmophilic, secretory granules localized in the myocardiocytes and called "atrial specific granules" (the atrial natriuretic factor, ANF). In this paper, the relationship between these specific granules and renovascular hypertension elicited by the constriction of both renal arteries was investigated at the electron microscope level during the acute, subacute and chronic phases of hypertension. Male Wistar CHbb THOM rats were divided in three groups: 1) clipped rats; 2) sham operated rats; 3) ether anesthesia as unique manoeuver 48 h before decapitation. Blood pressure increased progressively after the constriction of both renal arteries. The atrial specific granules were not affected by ether anesthesia alone; 48-72 h after clipping the granules almost disappeared and this situation persisted up to the 6th week. In sham operated rats the picture was very similar to the clip rats 48 and 72 h after surgery (severe granule disappearance); in contrast, at one, two and six weeks after surgery, the granularity of cardiomyocytes in sham rats was absolutely restored. It is concluded that: 1) similarities in morphology of atrial specific granules in sham and clip rats 48 and 72 h after surgery would suggest that stress plays a primary role in determining the observed images; 2) thereafter, the contrast between sham and clip rats 1, 2 and 6 weeks after surgery would indicate that the ANF is linked to the subacute and chronic regulation of renovascular hypertension.

Renal function conscious one kidney-one clip hypertensive rats. Effect of indomethacin.

These experiments have analyzed: a) Blood pressure (BP) and renal function in one kidney-one clip rats two weeks after clipping; b) The effect of cycloxygenase (CO) inhibition on BP and renal function regulation during the hypertensive period. Using the unanaesthetized, unrestrained and chronically instrumented animal, three groups of rats were studied: Sham, Clip 0.31 mm lumen and Clip 0.29 mm lumen. The animals were examined before (Control period) and during the infusion of indomethacin (IND, 5 mg/kg via aortic cannula, n = 11 for each group) or the buffer vehicle solution (BUF, n = 7 for each group). Effective inhibition of CO by IND was confirmed using radioimmunoassay of prostaglandin E2 (PGE2) in urine. Control BP (mmHg, mean +/- SE) differed significantly among the groups (p < 0.001): Sham, 114 +/- 3; Clip 0.31, 135 +/- 2; Clip 0.29, 154 +/- 4 and did not change by IND infusion. Along with the BP, Control Glomerular Filtration Rate and Renal Plasma Flow did not change by IND infusion, which suggests that CO eicosanoids, particularly PGG2, contribute little to basal renal hemodynamics in sham and hypertensive rats. Sodium excretion was lower in the Control period of Clip 0.29 rats (p < 0.01). A significant natriuretic effect observed in this Clip 0.29 group by the infusion of IND suggests the contribution of an AA related metabolite in renal handling of sodium in more severe renovascular hypertension.

Ultrastructural study of atrial specific granules in experimental renovascular hypertension elicited by the constriction of both renal arteries

El corazón tiene una actividad endocrina que depende de la secreción de un factor nafriurético, diurético e hipotensor contenido en gránulos osmiófilos secretorios localizados en los miocardiocitos y llamados " granulos atriales específicos" (atrial natriuretic factor, ANF). En este trabajo se investigó al microscópio electrónico la relación existente entre los gránulos atriales específicos y la hipertensión renovascular provocada por constricción de ambas arterias renales, examinándose los períodos agudo, subagudo y crónico de hipertensión. Se usaron ratas macho, Wistar CHbb Thom. Los animales fueron divididos en tres grupos: 1) ratas con compresión bilateral de la arteria renal; 2) ratas con operación simulada; 3) ratas con anestesia con éter como única maniobra, 48 hs antes de la decapitación. La presión arterial aumentó progresivamente después de la constricción de las arterias renales. Los gránulos atriales específicos no fueron afectados por la anestesia con éter. Por el contrário 48-72h después de la compresión de las arterias renales los gránulos atriales específicos prácticamente desaperecieron y esta situación persistía 1, 2 y 6 semanas después. En las ratas con operación simulada se observó un cuadro similar a las ratas con constricción arterial (severa desaparición de los gránulos) pero 1, 2 y 6 semanas más tarde la granularidad de los cardiomiocitos se había restaurado completamente. Se concluye: 1) la similitud de la respuesta en ratas con constricción de ambas arterias renales y en ratas con operación simulada 48-72 h después de la intervención sugiere que el estrés desempeña un papel inicial en los resultados observados. 2) el contraste observado 1, 2 y 6 semanas después entre ratas con constricción arterial pemanente y ratas con operación simulada indicaría que el factor natriurético atrial está vinculado con la regulación subaguda y crónica de la hipertensión renovascular

Ultrastructural study of atrial specific granules in experimental renovascular hypertension elicited by the constriction of both renal arteries.

The heart has an endocrine activity which depends on the secretion of a natriuretic, diuretic and hypotensive factor contained in osmophilic, secretory granules localized in the myocardiocytes and called [quot ]atrial specific granules[quot ] (the atrial natriuretic factor, ANF). In this paper, the relationship between these specific granules and renovascular hypertension elicited by the constriction of both renal arteries was investigated at the electron microscope level during the acute, subacute and chronic phases of hypertension. Male Wistar CHbb THOM rats were divided in three groups: 1) clipped rats; 2) sham operated rats; 3) ether anesthesia as unique manoeuver 48 h before decapitation. Blood pressure increased progressively after the constriction of both renal arteries. The atrial specific granules were not affected by ether anesthesia alone; 48-72 h after clipping the granules almost disappeared and this situation persisted up to the 6th week. In sham operated rats the picture was very similar to the clip rats 48 and 72 h after surgery (severe granule disappearance); in contrast, at one, two and six weeks after surgery, the granularity of cardiomyocytes in sham rats was absolutely restored. It is concluded that: 1) similarities in morphology of atrial specific granules in sham and clip rats 48 and 72 h after surgery would suggest that stress plays a primary role in determining the observed images; 2) thereafter, the contrast between sham and clip rats 1, 2 and 6 weeks after surgery would indicate that the ANF is linked to the subacute and chronic regulation of renovascular hypertension.

Renal function conscious one kidney-one clip hypertensive rats. Effect of indomethacin.

These experiments have analyzed: a) Blood pressure (BP) and renal function in one kidney-one clip rats two weeks after clipping; b) The effect of cycloxygenase (CO) inhibition on BP and renal function regulation during the hypertensive period. Using the unanaesthetized, unrestrained and chronically instrumented animal, three groups of rats were studied: Sham, Clip 0.31 mm lumen and Clip 0.29 mm lumen. The animals were examined before (Control period) and during the infusion of indomethacin (IND, 5 mg/kg via aortic cannula, n = 11 for each group) or the buffer vehicle solution (BUF, n = 7 for each group). Effective inhibition of CO by IND was confirmed using radioimmunoassay of prostaglandin E2 (PGE2) in urine. Control BP (mmHg, mean +/- SE) differed significantly among the groups (p < 0.001): Sham, 114 +/- 3; Clip 0.31, 135 +/- 2; Clip 0.29, 154 +/- 4 and did not change by IND infusion. Along with the BP, Control Glomerular Filtration Rate and Renal Plasma Flow did not change by IND infusion, which suggests that CO eicosanoids, particularly PGG2, contribute little to basal renal hemodynamics in sham and hypertensive rats. Sodium excretion was lower in the Control period of Clip 0.29 rats (p < 0.01). A significant natriuretic effect observed in this Clip 0.29 group by the infusion of IND suggests the contribution of an AA related metabolite in renal handling of sodium in more severe renovascular hypertension.