Sexual dysfunction and its determinants in women with rheumatoid arthritis.

OBJECTIVES: To evaluate sexual function in Tunisian women with rheumatoid arthritis (RA) and to examine factors that are predictors of female sexual dysfunction including sociocultural factors, disease activity, and psychological status. METHODS: We conducted a cross-sectional study including 71 women with a confirmed diagnosis of RA according to the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria. Clinical and sociodemographic characteristics were collected. The participants were asked to complete the Female Sexual Function Index (FSFI), which contains 19 questions, assessing six areas of female sexual function in the previous 4 weeks. Sexual dysfunction was defined as an FSFI score less than or equal to 26.55. The psychosocial status was evaluated by the Hospital Anxiety and Depression (HAD) scale. Prevalence of sexual dysfunction and predictors of sexual difficulties were assessed. RESULTS: The prevalence of female sexual dysfunction in women with RA was 49.3%. All areas were altered especially desire (2.92 ± 1.3), arousal (3.27 ± 1.5), and orgasm (3.77 ± 1.5). In univariate analysis, sexual dysfunction was correlated with the age of patients (p = 0.049), the age of partners (p = 0.013), pain (p = 0.001), number of night awakenings (p = 0.02), morning stiffness (p = 0.010), tender joints (p = 0.05), disease activity score (DAS28 ESR) (p = 0.043), fatigue (p = 0.028), and Health assessment questionnaire (HAQ) (p = 0.02). In multivariate analysis, the age of patients and pain were predictive factors of sexual dysfunction. By analyzing each area of the FSFI score, the age of patients was the independent variable associated with desire. Tender joints were associated with lubrication and the age of partners with arousal, orgasm, and satisfaction. CONCLUSION: Our study suggests that rheumatoid arthritis has a negative impact on patients' sexuality. Age of patients and partners, pain, and tender joints appear to be the main factors influencing sexual function.

Efficacy of local injection therapy for heel pain in rheumatic inflammatory diseases: A systematic review.

Heel pain or achillodynia is one of the most common manifestations in patients with rheumatic inflammatory diseases (RID) and particularly spondyloarthritis (SpA). It can be associated with inflammation at the bone insertion of tendon, ligament, bursa or fascia. However, treatment is still a challenge for rheumatologists. Several findings highlighted the proven benefit of nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and recently, tumor necrosis factor (TNF)-α inhibitors. However, only limited data about the efficacy of local therapy such as glucocorticoid and anti-TNF injections are available. The aim of this systematic review was to assess the efficacy and safety of local therapies in heel pain and to make recommendations for further studies. Five studies discussing the effectiveness of local treatments of heel pain in RID were included. All studies recognized that the ultrasonography (US)-guided local corticosteroid or etanercept injections were effective and safe modalities for the treatment of inflammatory heel enthesitis, tendinitis, and retrocalcaneal bursitis (RCB) in patients with RID. Pain relief at the local site was associated with a reversion of the acute inflammatory changes in the heel. Furthermore, US-guided injection in RCB with a lateral approach was beneficial in terms of preventing side effects.

[The changing face of rheumatoid arthritis]. / La polyarthrite rhumatoïde a-t-elle changé de visage au fil du temps ?

Rheumatoid arthritis (RA) is a heterogeneous disease in terms of presentation and evolution. In recent years, a change in the face of this disease has been noticed. RA appears to be less lethal than before, with a larger decline in cardiovascular mortality. Patient hospitalization and orthopedic surgery appear to be declining. Today's RA also seems less active and less destructive. These documented changes, especially over the last decade, are attributable not only to the emergence of biotherapies, but also to more rigorous management strategies by rheumatologists as well as increased patient awareness.

La polyarthrite rhumatoïde (PR) est une pathologie hétérogène dans sa présentation et son évolution. Au cours des dernières années, un changement du visage de cette maladie a été remarqué. Cette maladie semble être moins mortelle qu'avant, avec une baisse plus importante de la surmortalité cardiovasculaire. Le recours aux hospitalisations des patients et à la chirurgie orthopédique semble aussi en baisse. Les PR d'aujourd'hui paraissent aussi moins actives et moins destructrices. Ces changements, attestés surtout au cours de la dernière décennie, seraient attribuables non seulement à l'émergence des biothérapies, mais aussi à des stratégies de prise en charge des rhumatologues plus rigoureuses et une meilleure prise de conscience de la part des patients.

Undergraduate medical education in the Gulf Cooperation Council: a multi-countries study (Part 2).

BACKGROUND: The Gulf Cooperation Council (GCC) countries have witnessed over the last 40 years a rapid and major social, cultural, and economic transformation. The development of medical education in the region is relatively new, dating from the late 1960s. An important goal among the medical colleges in the region is to graduate national physicians who can populate the healthcare service of each country. AIM: The aim of this study is to provide understanding of undergraduate medical education in each of the six GCC countries and the challenges that each face. METHODS: This is a descriptive cross-sectional study. Fourteen senior medical faculty were requested to submit information about undergraduate medical education in their own countries, focusing on its historical background, student selection, curriculum, faculty, and challenges. RESULTS: The information provided was about 27 medical colleges: 16 from the Kingdom of Saudi Arabia (KSA), five from the United Arab Emirates, two from the Kingdom of Bahrain, two from Sultanate of Oman, one from Kuwait and one from the State of Qatar. It was found that older colleges are reviewing their curriculum while new colleges are developing their programs following current trends in medical education particularly problem-based learning and integrated curricula. The programs as described 'on paper' look good but what needs to be evaluated is the curriculum 'in action'. Faculty development in medical education is taking place in most of the region's medical colleges. CONCLUSION: The challenges reported were mainly related to shortages of faculty, availability of clinical training facilities, and the need to more integration with the National Health Care services. Attention to quality, standards, and accreditation is considered essential by all colleges.

Undergraduate medical education in the Gulf Cooperation Council: a multi-countries study (Part 1).

BACKGROUND: The Gulf Cooperation Council (GCC) countries have witnessed over the last 40 years a rapid and major social, cultural, and economic transformation. The development of medical education in the region is relatively new, dating from the late 1960s. An important goal among the medical colleges in the region is to graduate national physicians who can populate the healthcare service of each country. AIM: The aim of this study is to provide understanding of undergraduate medical education in each of the six GCC countries and the challenges that each face. METHODS: This is a descriptive cross-sectional study. Fourteen senior medical faculty were requested to submit information about undergraduate medical education in their own countries, focusing on its historical background, student selection, curriculum, faculty, and challenges. RESULTS: The information provided was about 27 medical colleges: 16 from the Kingdom of Saudi Arabia (KSA), five from the United Arab Emirates (UAE), two from the Kingdom of Bahrain, two from Sultanate of Oman, one from Kuwait, and one from the State of Qatar. It was found that older colleges are reviewing their curriculum while new colleges are developing their programs following current trends in medical education, particularly problem-based learning and integrated curricula. The programs as described 'on paper' look good but what needs to be evaluated is the curriculum 'in action'. Faculty development in medical education is taking place in most of the region's medical colleges. CONCLUSION: The challenges reported were mainly related to shortages of faculty, availability of clinical training facilities and the need to more integration with the National Health Care services. Attention to quality, standards, and accreditation is considered essential by all colleges.

Comparison of sexual function in Tunisian women with rheumatoid arthritis and healthy controls.

OBJECTIVES: To evaluate sexual function in Tunisian women with rheumatoid arthritis (RA) and to compare it with that in voluntary healthy controls. METHODS: We conducted a cross-sectional study including 71 women with a confirmed diagnosis of RA according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 Criteria and 71 healthy age-matched controls. Clinical and sociodemographic characteristics were collected. Patients and controls were asked to complete the Female Sexual Function Index (FSFI). It contains 19 questions, assessing six areas of female sexual function in the previous 4 weeks. The sexual dysfunction was defined as an FSFI score less than or equal to 26.55. The patients' self-perception of their sexuality was assessed, and the frequency of sexual intercourse was noted. RESULTS: The prevalence of female sexual dysfunction in women with RA was 49.3% versus 23.9% in controls, with a significant difference (p = 0.002). Comparison between both groups as regards the mean of area scores of FSFI revealed that desire, arousal, and satisfaction in patients with RA were significantly lower than those in the control group (p = 0.05, p = 0.038, and p = 0.024, respectively). The score of lubrification, orgasm, and pain was comparable between the two groups. In univariate analysis, a significant association was found between sexual dysfunction and pain (p = 0.001), tender joint counts (p = 0.04), DAS28 ESR (p = 0.043), fatigue (p = 0.028), and functional disability (p = 0.02). No association was found between sexual dysfunction and treatment. In multivariate analysis, only pain was a predictive factor of sexual dysfunction in patients (p = 0.05, OR = 1.26 [1.16-1.3]). Based on patients' self-perception of their sexual function, 26.1% of patients reported a negative impact of RA on their sex life. According to them, the main factors influencing sexuality were joint pain (60.6%) and fatigue (51%). Moreover, 59% of patients reported a decrease in the frequency of sexual intercourse after the diagnosis of RA. However, no statistically significant difference was found between patients and controls in the frequency of sexual intercourse (p = 1). CONCLUSION: Our study suggests that patients with RA experience high level of impairment of sexual function in comparison with a control group. Health providers must consider sexual function as an important part of quality of life. A therapeutic education directed towards a patient could be proposed to approach sexuality.Key Points• The prevalence of female sexual dysfunction is higher in women with rheumatoid arthritis than in controls.• In multivariate analysis, the global pain intensity visual analog scale was the only predictive factor of sexual dysfunction in patients.• Based on patients' self-perception, joint pain and fatigue are the main factors influencing sexuality.

Tetrastischus howardi density and dispersal toward augmentation biological control of sugarcane borer.

The number of Tetrastischus howardi (Olliff) females to be released and their dispersion should be known, that way, used D. saccharalis pupae as sentinel host to measure parasitism as function of the release density of the parasitoid and its location in the field. Two sets of trials were run aiming first to define the number of parasitoids to be released and the dispersal of the parasitoid using plots in sugarcane commercial fields, respectively. Pieces of sugarcane stalk holding sentinel pupae were taken to the field and exposed to parasitism in both trials. The parasitoid was released at the rate of 20, 40, 80, and 160 females per sentinel pupa, except for the control plot without releasing. The parasitism rate was calculated based on the recovered pupae after 96 h of exposure time from releasing the parasitoids. The models estimated the best parasitism rate by releasing 102 parasitoids per pupa. In the second trial, sentinel pupae were arranged in five subsequent circles corresponding 4, 8, 12, 16, and 20 m around the central parasitoid releasing point at rate of 4, 8, 12, 16, and 18 pupae per circle. The mean estimated dispersal distance was 7.64 m, with a covering area of 80.07 m2. Based on these findings, release of T. howardi is recommended in 125 points per hectare of sugarcane at rate of 102 females per pupa of the pest aiming to achieve homogeneous distribution and parasitism.

Clinical and biological features of enteroviral meningitis among adults and children and factors associated with severity and length of stay.

BACKGROUND: Enterovirus (EV) meningitis is the most common form of meningitis. Clinical and biological manifestations may be non-specific, leading to prolonged and costly investigations. OBJECTIVES: To determine the different aspects of EV meningitis and the variables associated with length of stay (LOS) in hospital independently of patients' age. STUDY DESIGN: Single center retrospective study of all EV PCR positive CSF samples during 3.5 years in Bordeaux University Hospital, France. RESULTS: 172 patients were included. 65 were under 3 years old and 49 over 18 years old. 10% of patients had severe forms of the disease. 47 patients (27.3%) had normal CSF count and in 63 patients (36.6%) polynuclear cells predominated in CSF. Procalcitonin, Hoens' score or PCR in stool samples appeared as good markers for enteroviral diagnosis. Time elapsed before PCR results was associated with LOS (p = .002) and should help in limiting investigations in case of aseptic meningitis. CONCLUSION: Rapid availability of EV PCR reduces LOS for patients and contributes to diminish unnecessary procedures and further tests.

[Juvenile idiopathic arthritis treated by methotrexate: result of treatment and tolerance]. / Les arthrites juvéniles idiopathiques traitées par méthotrexate. réponse au traitement et tolerance à moyen terme.

The MTX has a place of choice in the treatment of the AJI with good observance and the absence of grave side effects. In a retrospective study, 14 cases of AJI having benefited from a treatment by MTX were included in the study. Answer to the treatment was estimated at the 6-th month on the criteria of RINTO. The group included in the therapeutic evaluation, is formed by 10 boys and by 4 girls. The average age of the beginning of the disease is of 6 years (2 - 11). The shape of the beginning is systematic in 7 cases and polyarticular in 5 cases and oligoarticular in 2 cases.. The average duration of the treatment by MTX is of 36 months (9 - 66). Answer to the MTX in the 6-th month was noted in 7 cases, under a MTX's average dose of 7, 14mg / m2 / week. Unwanted effects were observed in 7 cases and have not in any case led to the stop of the treatment

Role of ultrasound in assessing remission in rheumatoid arthritis.

INTRODUCTION: Remission is the ultimate goal of the treatment of rheumatoid arthritis (RA). However, the diagnosis of remission might still be vague. Musculoskeletal ultrasound (US) seems to effectively assess synovitis, effusion and bone damage. Thus, its role could be relevant for the diagnosis, monitoring or detection of relapse in the follow-up of RA in remission. The goal of this review of the literature was to clarify the added value of ultrasonography during remission. METHODS: A systemic search of the literature was performed on Medline and Scopus. The following key words were used: rheumatoid arthritis, remission, US. Fifty-six papers were collected, then after an in depth analysis, twelve articles were selected for analysis. RESULTS: Twelve papers were identified that assessed remission in RA. Remission criteria varied from one author to another. The number of joints assessed by US varied from six to 44 with the wrist and metacarpo-phalangeal joints of the dominant hand scanned at least. Irrespective of remission criteria, all authors demonstrated that US detected Doppler positive synovitis in patients in clinical remission. Also, power Doppler synovitis predicted structural damage and future flares of RA. CONCLUSION: US seems to be more effective than a clinical exam. True remission in RA must be defined. Moreover, the inclusion of this technique in the new definition of remission is being validated.

Role of endothelin in mediating the attenuated renal hemodynamics in Dahl salt-sensitive hypertension.

The aim of this study was to evaluate the role of endothelin (ET) in the hypertension associated with giving a high sodium diet in Dahl salt-sensitive (DS) rats. To achieve this goal, we examined the effects of intravenous infusion of the nonspecific ET(A)-ET(B) antagonist on arterial pressure and renal function in conscious, chronically instrumented DS and Dahl salt-resistant (DR) rats. After 3 weeks on a high sodium (8%) diet, mean arterial pressure (MAP) in DS rats (166+/-3 mm Hg) was significantly higher than in DR rats (124+/-3 mm Hg). Baseline glomerular filtration rate (GFR) and renal plasma flow (RPF) in DS rats (1.92+/-0.25 mL/min and 7.07+/-0.80 mL/min) were lower than in DR rats (2.52+/-0.21 mL/min and 7.98+/-0.85 mL/min), respectively. Renal vascular resistance was significantly higher in DS rats (32.78+/-5.88 mm Hg x mL(-1) x min(-1)) than in DR rats (24.60+/-5.04 mm Hg x mL(-1) x min(-1)). Intravenous infusion of the ET antagonist SB 209670 at a dose of 30 microg x kg(-1) x min(-1) for 75 minutes caused a significant decrease in MAP in DS rats (from 166+/-3 to 144+/-4 mm Hg). In contrast, the effect of the ET antagonism on MAP in DR rats was not significant. ET-antagonist infusion tended to improve GFR and RPF in DS but not in DR rats. To determine the renal effects of ET antagonism independent of the systemic hemodynamic responses, we examined the effects of the same ET antagonist in rats chronically implanted with a renal interstitial catheter. Arterial pressure in DS rats (181+/-5 mm Hg) was significantly higher than in DR rats (135+/-3 mm Hg). Renal interstitial infusion of SB 209670 at a dose of 200 ng x kg(-1) x min(-1) for 60 minutes caused no change in MAP in DS or DR rats. Intrarenal ET antagonism significantly increased GFR (25%), RPF (30%), urine flow (32%), and urinary sodium excretion (25%) in DS rats, while it had no significant effect in DR rats. Fractional excretion of sodium was not significantly changed by renal interstitial infusion of the ET antagonist in DS rats, indicating that improved renal excretory function in DS rats is most likely due to the associated improvement in renal hemodynamics. We conclude that ET may play a role in the attenuated renal hemodynamics and possibly the development of Dahl salt-sensitive hypertension.

Endothelin antagonists improve renal function in spontaneously hypertensive rats.

Hypertension in the spontaneously hypertensive rat (SHR) is associated with reduced renal excretory function, low renal plasma flow, reduced glomerular filtration rate, and reduced renal interstitial hydrostatic pressure. The mechanisms responsible for these abnormalities in renal function are unknown. The purpose of this study was to determine the role of intrarenal endothelin in altering renal hemodynamic and excretory function in the SHR. Both PD 145065 (an endothelin A and B receptor antagonist) and FR 139317 (a selective endothelin A receptor antagonist) or saline was infused into the renal interstitium of 14- to 16-week-old SHR (n = 7) and age-matched Wistar-Kyoto rats (WKY) (n = 7). Renal perfusion pressure in some SHR was reduced to that of the WKY by a servocontrol system. At a renal perfusion pressure of 124 +/- 4 mm Hg, infusion of PD 145065. (0.03 mg.kg-1.min-1) and FR 139317 (0.02 mg.kg-1.min-1) significantly increased glomerular filtration rate (delta 22%), renal plasma flow (delta 37%), and renal interstitial hydrostatic pressure (from 3.2 +/- 0.5 to 5.4 +/- 0.6 mm Hg) in the SHR. These changes were associated with significant increases in urine flow, absolute sodium excretion, and fractional excretion of sodium. Similar improvements in renal plasma flow, renal interstitial hydrostatic pressure, and renal excretory function were obtained in the SHR whose renal perfusion pressure was not reduced (n = 7). Renal interstitial infusion of endothelin receptor antagonists had no effect on renal hemodynamic or excretory function in the WKY. These data demonstrate that endothelin receptor blockade within the kidney improves renal hemodynamic and excretory function in the SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal denervation attenuates the sodium retention and hypertension associated with obesity.

Recent studies have indicated that obesity is associated with hypertension, sodium retention, and increased sympathetic nervous system activity. The purpose of this study was to determine the role of renal nerves in mediating the sodium retention and hypertension associated with obesity. We determined the hemodynamic and renal excretory responses to a high-fat diet in control (n = 6) and bilaterally renal-denervated (n = 7) chronically instrumented dogs. After a control period of 8 days, dogs were placed on a high-fat diet for 5 weeks. In response to a high-fat diet, body weight increased from 19.9 +/- 2.2 to 29.9 +/- 2.4 kg in the control group and from 21.1 +/- 2.0 to 32.4 +/- 1.9 kg in the bilaterally renal-denervated group. Heart rate increased from 81 +/- 8 to 113 +/- 7 beats per minute in the control group and from 79 +/- 7 to 103 +/- 8 beats per minute in the bilaterally renal-denervated group. Arterial pressure increased significantly from 95 +/- 2 to 109 +/- 4 mm Hg in the control group. In contrast, 5 weeks of a high-fat diet in the bilaterally renal-denervated group did not significantly increase arterial pressure (which went from 87 +/- 3 to 90 +/- 4 mm Hg). Furthermore, the decrease in sodium excretion in response to the high-fat diet was significantly greater in the control group than in the bilaterally renal-denervated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of nitric oxide in modulating the long-term renal and hypertensive actions of norepinephrine.

We have previously reported that nitric oxide (NO) plays an important role in protecting the renal vasculature from acute norepinephrine-induced vasoconstriction. The purpose of this study was to determine the importance of this interaction between NO and norepinephrine in long-term control of renal hemodynamics and arterial pressure. To achieve this goal, we examined the effects of an intrarenal infusion of norepinephrine (NE) (0.1 microgram.kg-1.min-1) for 7 days in conscious, chronically instrumented control dogs and in dogs pretreated with a synthesis inhibitor, L-NAME (3 micrograms.kg-1.min-1 intrarenally). Both groups of dogs also received captopril (15 micrograms.kg-1.min-1) plus angiotensin I] intravenously to clamp the renin-angiotensin system throughout the protocol. In control dogs (n = 6), intrarenal infusion of NE decreased renal plasma flow by 9% (134 +/- 10 to 122 +/- 14 mL/min) and glomerular filtration rate by 16% (49 +/- 4 to 41 +/- 5 mL/min) while having no effect on mean arterial pressure (100 +/- 3 to 98 +/- 4 mm Hg). In marked contrast, in dogs pretreated with intrarenal L-NAME (n = 9), NE decreased renal plasma flow by 37% (129 +/- 8 to 81 +/- 16 mL/min) and glomerular filtration rate by 32% (47 +/- 3 to 32 +/- 5 mL/min) while increasing mean arterial pressure from 104 +/- 5 to 113 +/- 6 mm Hg. The results of this study demonstrate that NO plays an important role in modulating the long-term actions of NE on renal function and arterial pressure.

Reduced sensitivity of the renal circulation to angiotensin II in pregnant rats.

The renal circulation undergoes significant changes during pregnancy and pregnancy-induced hypertension. Although numerous studies indicate that the pressor response to angiotensin II (Ang II) is reduced during pregnancy, it is unclear as to whether this altered sensitivity to Ang II occurs in the renal circulation. The first aim of this study was to determine whether the renal vascular responsiveness to exogenous Ang II is altered in the midterm pregnant rat. All rats were pretreated with an intravenous infusion of the converting-enzyme inhibitor captopril (20 microg x kg(-1) x min(-1)) to block endogenous Ang II formation. Following a control period, Ang II was infused at a dose of 10 ng x kg(-1) x min(-1) for 50 minutes into the renal arteries via a suprarenal aortic catheter. In anesthetized virgin rats, Ang II markedly decreased renal plasma flow (RPF) by 39% (5.0+/-0.4 to 3.1+/-0.4 mL/min), glomerular filtration rate (GFR) by 39% (1.9+/-0.1 to 1.16+/-0.2 mL/min), and urine flow by 47% (22.1+/-5.6 to 12.3+/-4.8 microL/min). In contrast, Ang II had no significant effect on RPF, GFR, and urine flow in the anesthetized pregnant rats. Since nitric oxide (NO) has been previously reported to modulate the renal vascular actions of Ang II in normal animals and NO synthesis is thought to be elevated in pregnancy, this study examined the role of NO in the attenuated renal response to Ang II. In pregnant rats pretreated with L-NAME, the arterial pressure was higher and RPF was lower than in the control pregnant rats. However, the renal response to Ang II in the L-NAME-pretreated pregnant rats was similar to control pregnant rats. These data indicate that the renal circulation has a reduced sensitivity to Ang II during pregnancy. We also found that NO synthesis inhibition does not alter the attenuated renal response to Ang II in the anesthetized pregnant rats.

Systemic hemodynamics and regional blood flow during chronic nitric oxide synthesis inhibition in pregnant rats.

Pregnancy-induced hypertension in women is associated with severe vasoconstriction and reductions in organ blood flow and cardiac output. Recent studies have indicated that nitric oxide (NO) synthesis inhibition during mid to late gestation in pregnant rats results in severe hypertension and proteinuria. The purpose of this study was to determine the systemic hemodynamic and regional blood flow alterations associated with chronic NO synthesis inhibition in the pregnant rat. The study was conducted in four groups of rats: virgin rats (n=6), pregnant rats (n=10), virgin rats treated with L-NAME (n=6), and pregnant rats treated with L-NAME (n=11). Rats were treated with L-NAME in drinking water at a dose of 1 mg/d for a week starting from day 13 of gestation in pregnant rats or an equivalent time for virgins. Mean arterial pressure (MAP), cardiac output, total peripheral resistance (TPR), and regional flows were measured by tracing radiolabeled microspheres in conscious rats. Pregnant rats that were given L-NAME showed significantly higher MAP (137+/-6 versus 96+/-2 mm Hg), higher TPR (5.08+/-0.58 versus 2.90+/-0.44 mm Hg/mL/min/100 g), and lower cardiac output (87.4+/-8.4 versus 113.3+/-11.1 mL/min) than pregnant controls. Chronic NO synthesis inhibition decreased the renal blood flow in pregnant rats at a significantly greater magnitude than in virgin rats. Significant reductions in regional blood flow to the heart, lungs, liver, diaphragm, and skeletal muscles were also observed in pregnant rats treated with L-NAME. The results of this study indicate that NO may play a role in mediating the alterations in systemic hemodynamics and regional blood flow in late pregnant rats.

Endothelin-A receptor antagonism attenuates the hypertension and renal injury in Dahl salt-sensitive rats.

The aim of this study was to examine the role of endothelin-A (ET(A)) receptors in mediating the hypertension and renal injury associated with high salt intake in Dahl salt-sensitive (DS) rats. To achieve this goal, we examined the effects of chronic selective ET(A) antagonist (A-127722) treatment at a dose of 10 mg/kg/d on arterial pressure, renal function, and morphology in DS and Dahl salt-resistant (DR) rats placed on a high sodium (8% NaCl) diet (HSD) for 3 weeks. Placement of DS rats (n=13) on HSD for 3 weeks caused a progressive increase in systolic pressure (from 118+/-3 to 186+/-15 mm Hg). The increase in systolic pressure was significantly attenuated (from 125+/-4 to 167+/-12 mm Hg) in DS rats treated with A-127722 (n=13). Mean arterial pressure (MAP) measured directly at the end of the study was also significantly lower by 18 mm Hg (P<.02) in the DS rats treated with A-127722. The slope of the chronic pressure-natriuresis curve was shifted to the right in DS rats and to the left by chronic ET(A) receptor blockade in DS rats. The hypertension in DS rats was associated with marked proteinuria (from 4.1+/-1.1 to 74.3+/-5.3 mg/24 h/100 g body weight) that was significantly attenuated (from 5.7+/-1.2 to 55.2+/-6.5 mg/24 h/100 g body weight) in DS rats treated with A-127722. The percentage of glomeruli displaying fibrosis, hypercellularity, and hyalinization was also significantly reduced after treatment with A-127722 in DS rats. Arterial pressure, protein excretion, renal hemodynamics, and morphologic structure were not significantly changed in response to ET(A) receptor blockade in DR rats placed on HSD. These data indicate that endothelin-A receptor activation may play a role in the exacerbation of hypertension and development of renal injury in DS rats.

Enhanced vascular reactivity during inhibition of nitric oxide synthesis in pregnant rats.

Pregnancy-induced hypertension has been suggested to be mediated by several mechanisms, including reduced nitric oxide (NO) synthesis. In this study, the effects of chronic treatment with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on blood pressure and the underlying changes in vascular reactivity were investigated in virgin and late-pregnancy Sprague-Dawley rats. The systolic blood pressure was 120+/-2, 124+/-5, 116+/-4, and 171+/-5 mm Hg in untreated virgin, virgin treated with L-NAME, untreated pregnant, and pregnant treated with L-NAME rats, respectively. The rats were killed, and the thoracic aorta was cut into strips for measurement of active stress in response to alpha1-adrenergic stimulation with phenylephrine and membrane depolarization by high KCl. In pregnant rats, the maximal active stress to phenylephrine (0.31+/-0.03 x 10(4) N/m2) and the high-KCl-induced active stress (0.55+/-0.09 x 10(4) N/m2) were smaller than those in virgin rats. By contrast, in the L-NAME-treated pregnant rats, the maximal phenylephrine-induced active stress (0.76+/-0.1 x 10(4) N/m2) was greater than that in virgin rats (0.52+/-0.1 x 10(4) N/m2), whereas the high-KCl-induced active stress (1.08+/-0.14 x 10(4) N/m2) was indistinguishable from that in virgin rats (1.03+/-0.14 x 10(4) N/m2). Treatment with L-NAME did not affect the phenylephrine-releasable Ca2+ stores in pregnant rats and had minimal effect on active stress in virgin rats. Thus, reduction of NO synthesis during late pregnancy is associated with a significant increase in blood pressure and vascular responsiveness to alpha-adrenergic stimulation, which can possibly be explained in part by enhanced Ca2+ entry from extracellular space. However, other mechanisms such as increased myofilament force sensitivity to Ca2+ and/or activation of a completely Ca2+-independent mechanism cannot be excluded.

Decreased sensitivity to renal interstitial hydrostatic pressure in Dahl salt-sensitive rats.

The ability of Dahl salt-sensitive (DS) rats to excrete a sodium load is significantly lower than Dahl salt-resistant (DR) rats. Because renal interstitial hydrostatic pressure (RIHP) is a major mediator of natriuresis in response to a sodium load, we proposed that the renal tubules of DS rats are less responsive to increases in RIHP than those of DR rats. To test this hypothesis, we determined the effect of direct increases in RIHP on renal excretory function in prehypertensive DS and DR rats. RIHP was directly increased by renal interstitial volume expansion via injection of 50 microL of a 2% albumin and saline solution into the renal interstitium through a chronically implanted renal interstitial catheter. RIHP, mean arterial pressure, glomerular filtration rate, urine flow rate, urinary sodium excretion, and fractional excretions of sodium, potassium, and lithium (an indicator of proximal tubule sodium handling) were measured before and after direct increases in RIHP in DS (n = 8) and DR (n = 8) rats. Baseline urine flow rate; urinary sodium excretion; fractional excretions of sodium, potassium, and lithium; RIHP; mean arterial pressure; and glomerular filtration rate were not different between DS and DR rats. Renal interstitial volume expansion in DS rats significantly increased RIHP (delta 4.7 +/- 0.8 mm Hg), urine flow rate (delta 14.5 +/- 3.4 microL/min), urinary sodium excretion (delta 2.62 +/- 0.62 mumol/min), and fractional excretions of sodium (delta 1.54 +/- 0.37%), potassium (delta 17.84 +/- 2.90%), and lithium (delta 19.68 +/- 3.52%).(ABSTRACT TRUNCATED AT 250 WORDS)

Blunted natriuretic response to a high-sodium meal in obese dogs. Role of renal nerves.

Although the relation between body weight and arterial pressure is well established, the mechanisms involved in the pathogenesis of obesity-related hypertension are unclear. However, recent studies suggest that abnormalities in renal function may be involved. The purpose of this study was to test the hypothesis that obese animals have a reduced ability to excrete a sodium load as a result of abnormal renal nerve function. To quantify the role of renal nerves, we examined changes in renal hemodynamics and sodium excretion in response to a high-sodium meal (200 mmol Na) in separate innervated and denervated kidneys simultaneously within the same conscious dog. Two surgically designed hemibladders with indwelling catheters were used to collect urine from innervated and denervated kidneys of the same dog. Body weight averaged 19.9 +/- 1.0 kg in the control lean dogs and 25.1 +/- 1.1 kg in the obese dogs. Arterial pressure averaged 101 +/- 4 mm Hg in the obese dogs and 90 +/- 4 mm Hg in the lean dogs. In response to the high-sodium meal in lean dogs, urinary sodium excretion increased from 20.8 +/- 4.2 to 189.7 +/- 21.2 mumol/min in the innervated kidneys and from 25.3 +/- 5.9 to 194.8 +/- 26.9 mumol/min in the denervated kidneys. In contrast, urinary sodium excretion in obese dogs increased from 9.6 +/- 1.4 to 129.9 +/- 34.3 mumol/min in the innervated kidneys and from 18.4 +/- 3.7 to 125.2 +/- 30.5 mumol/min in the denervated kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)