NaHCO(3) and KHCO(3) ingestion rapidly increases renal electrolyte excretion in humans.
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This paper describes and quantifies acute responses of the kidneys in correcting plasma volume, acid-base, and ion disturbances resulting from NaHCO(3) and KHCO(3) ingestion. Renal excretion of ions and water was studied in five men after ingestion of 3.57 mmol/kg body mass of sodium bicarbonate (NaHCO(3)) and, in a separate trial, potassium bicarbonate (KHCO(3)). Subjects had a Foley catheter inserted into the bladder and indwelling catheters placed into an antecubital vein and a brachial artery. Blood and urine were sampled in the 30-min period before, the 60-min period during, and the 210-min period after ingestion of the solutions. NaHCO(3) ingestion resulted in a rapid, transient diuresis and natriuresis. Cumulative urine output was 44 +/- 11% of ingested volume, resulting in a 555 +/- 119 ml increase in total body water at the end of the experiment. The cumulative increase (above basal levels) in renal Na(+) excretion accounted for 24 +/- 2% of ingested Na(+). In the KHCO(3) trial, arterial plasma K(+) concentration rapidly increased from 4.25 +/- 0.10 to a peak of 7.17 +/- 0.13 meq/l 140 min after the beginning of ingestion. This increase resulted in a pronounced, transient diuresis, with cumulative urine output at 270 min similar to the volume ingested, natriuresis, and a pronounced kaliuresis that was maintained until the end of the experiment. Cumulative (above basal) renal K(+) excretion at 270 min accounted for 26 +/- 5% of ingested K(+). The kidneys were important in mediating rapid corrections of substantial portions of the fluid and electrolyte disturbances resulting from ingestion of KHCO(3) and NaHCO(3) solutions. (+info)
Exercise exacerbates acute mountain sickness at simulated high altitude.
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We hypothesized that exercise would cause greater severity and incidence of acute mountain sickness (AMS) in the early hours of exposure to altitude. After passive ascent to simulated high altitude in a decompression chamber [barometric pressure = 429 Torr, approximately 4,800 m (J. B. West, J. Appl. Physiol. 81: 1850-1854, 1996)], seven men exercised (Ex) at 50% of their altitude-specific maximal workload four times for 30 min in the first 6 h of a 10-h exposure. On another day they completed the same protocol but were sedentary (Sed). Measurements included an AMS symptom score, resting minute ventilation (VE), pulmonary function, arterial oxygen saturation (Sa(O(2))), fluid input, and urine volume. Symptoms of AMS were worse in Ex than Sed, with peak AMS scores of 4.4 +/- 1.0 and 1.3 +/- 0.4 in Ex and Sed, respectively (P < 0.01); but resting VE and Sa(O(2)) were not different between trials. However, Sa(O(2)) during the exercise bouts in Ex was at 76.3 +/- 1.7%, lower than during either Sed or at rest in Ex (81.4 +/- 1.8 and 82.2 +/- 2.6%, respectively, P < 0.01). Fluid intake-urine volume shifted to slightly positive values in Ex at 3-6 h (P = 0.06). The mechanism(s) responsible for the rise in severity and incidence of AMS in Ex may be sought in the observed exercise-induced exaggeration of arterial hypoxemia, in the minor fluid shift, or in a combination of these factors. (+info)
Effects of systemic inhibition of neuronal nitric oxide synthase in diabetic rats.
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Diabetes is associated with alterations in nitric oxide-mediated vasomotor function. The role of nitric oxide generated via the neuronal nitric oxide synthase pathway in the control of systemic and renal hemodynamics in diabetes has not been studied. To explore the hypothesis that diabetic vascular dysfunction is in part caused by altered neuronal nitric oxide synthase activity, systemic and renal hemodynamics were assessed before and after acute inhibition of this enzyme with a specific inhibitor, S-methyl-L-thiocitrulline, in control and diabetic rats. The interaction of this pathway and the renin-angiotensin system was studied in separate groups of rats pretreated with the angiotensin II receptor blocker losartan; these rats were compared with rats treated with losartan alone. Diabetic animals demonstrated higher baseline glomerular filtration rates and filtration fractions. At a low dose, the neuronal nitric oxide synthase inhibitor induced similar dose-dependent pressor responses in control and diabetic rats. Losartan abolished the pressor response in both groups. No changes in renal plasma flow or renal vascular resistance occurred in control rats. In contrast, diabetic rats responded with significant renal vasoconstriction. At a high dose, the renal vasoconstriction was similar in both groups and was not affected by losartan. In conclusion, neuronal nitric oxide synthase-derived nitric oxide plays a role in the control of systemic and renal hemodynamics in normal and diabetic rats. Diabetic rats are more sensitive to the inhibitor, suggesting increased activity of this pathway in the diabetic kidney. Furthermore, renal responses in diabetic rats were attenuated by angiotensin II receptor blockade, whereas losartan alone induced hemodynamic changes that were opposite those seen with neuronal nitric oxide synthase inhibition. This observation implicates angiotensin II as an important modulator of this nitric oxide pathway in diabetes. (+info)
Walking with labor epidural analgesia: the impact of bupivacaine concentration and a lidocaine-epinephrine test dose.
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BACKGROUND: Regional analgesia techniques for labor that permit ambulation are popular among parturients. This study evaluated the influence of bupivacaine bolus concentration and a 3-ml 1.5% lidocaine-epinephrine test dose, on analgesic effectiveness and the ability to walk after block placement. METHODS: Using a randomized double-blind study design, epidural analgesia was initiated in 60 parturients undergoing labor as follows: Group TD/B.0625 received a 3-ml lidocaine-epinephrine test dose + 12 ml bupivacaine, 0.0625%; group TD/B.125 received a 3-ml test dose + 12 ml bupivacaine, 0.125%; group B.0625 received 15 ml bupivacaine, 0.0625% (no test dose); and group B.125 received 15 ml bupivacaine, 0.125% (no test dose). Initial boluses in all groups contained 10 microg sufentanil. Bupivacaine, 0.0625%, with 0.33 microg/ml sufentanil was infused throughout labor at 13.5-15 ml/h. Analgesia balance, proprioception, motor block, and patient ability to stand and walk were evaluated at various intervals. RESULTS: A bolus of 0.125% bupivacaine containing sufentanil, without a previous test dose, proved to be optimal with respect to analgesia and early ambulation. When a test dose was given before bupivacaine, 0.125%, fewer women walked within 1 h of block placement. Bupivacaine, 0.0625%, with sufentanil, with or without a test dose, provided inadequate analgesia, necessitating additional bupivacaine, which impaired the ability to walk. A high percentage of women in all groups (73-93%) walked at some stage during labor. CONCLUSIONS: Omitting a lidocaine-epinephrine test dose and using 0.125% bupivacaine for the initial bolus should permit ambulation in the early postblock period for most parturients who elect this option. (+info)
Alpha blocker prazosin for the treatment of benign prostatic hypertrophy (BPH).
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In this study medical treatment with alpha blocker-prazosin is compared with transurethral resection of prostate (TURP) in 62 patients suffering from benign enlargement of prostate with a gland size of less than 20 gms. After thorough interrogation patients were offered either TURP or prazosin therapy. Symptom scoring, residual volume of urine and urinary flow rates were estimated in both the groups before and 3 months after the therapy. 23.5% patients in prazosin group while 90% of patients in TURP group had significant improvement. This distinctly brings out the superiority of TURP for benign enlargement of prostate. (+info)
Non-linear membrane properties of sacral sphincter motoneurones in the decerebrate cat.
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1. Responses to pudendal afferent stimulation and depolarizing intracellular current injection were examined in sacral sphincter motoneurones in decerebrate cats. 2. In 16 animals examined, 2-10 s trains of electrical stimulation of pudendal afferents evoked sustained sphincter motoneurone activity lasting from 5 to >50 s after stimulation. The sustained response was observed in: 11 animals in the absence of any drugs; two animals after the intravenous administration of 5-hydroxytryptophan (5-HTP; <= 20 mg kg-1); one animal in which methoxamine was perfused onto the ventral surface of the exposed spinal cord; and two animals following the administration of intravenous noradrenergic agonists. 3. Extracellular and intracellular recordings from sphincter motoneurones revealed that the persistent firing evoked by afferent stimulation could be terminated by motoneurone membrane hyperpolarization during micturition or by intracellular current injection. 4. Intracellular recordings revealed that 22/40 sphincter motoneurones examined displayed a non-linear, steep increase in the membrane potential in response to depolarizing ramp current injection. The mean voltage threshold for this non-linear membrane response was -43 +/- 3 mV. Five of the 22 cells displaying the non-linear membrane response were recorded prior to the administration of 5-HTP; 17 after the intravenous administration of 5-HTP (<= 20 mg kg-1). 5. It is concluded that sphincter motoneurones have a voltage-sensitive, non-linear membrane response to depolarization that could contribute to sustained sphincter motoneurone firing during continence. (+info)
Single dose methodology to assess the influence of an alpha1-adrenoceptor antagonist on uroflowmetric parameters in patients with benign prostatic hyperplasia.
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AIMS: To establish methodology which rapidly and reliably assesses the effect of an alpha1-adrenoceptor antagonist on peak urine flow rates in men with benign prostatic hyperplasia (BPH). This methodology could then be applied to screening new drugs to treat BPH. METHODS: Twenty-five patients with BPH enrolled in a double-blind, placebo-controlled, two-period crossover study. Patients were either withdrawn from their current alpha1-adrenoceptor antagonist therapy (n = 22) or were untreated prestudy (n = 3) and all met prespecified uroflowmetric criteria including: (1) a peak urine flow rate (Qmax) < 12 ml s-1 off therapy (or < 10 ml s-1 if untreated prestudy) and (2) a decrease in peak urine flow rate (Qmax) of > 2 ml s-1 after withdrawal from therapy. Study treatment consisted of tamsulosin 0.4 mg (or matching placebo) once daily for 8 days in a two-period crossover. Uroflowmetry was performed predose and once postdose (4.5-5.5 h postdose) on day 1, and once postdose (4.5-5.5 h postdose) on day 8 of each treatment period. RESULTS: After a single dose of tamsulosin, the least-square mean difference between tamsulosin and placebo in the change from baseline Qmax was 2.8 ml s-1 (P = 0.017 vs placebo). After 8 days dosing of tamsulosin, the least-square mean difference between tamsulosin and placebo in the change from baseline Qmax was also 2.8 ml s-1 (P = 0.044 vs placebo). Additionally, there was no significant difference observed between the single and multiple dose results (P > 0.200 for between group difference). CONCLUSIONS: Both single and multiple doses of tamsulosin 0.4 mg increased Qmax in men with BPH. A single dose produced a comparable response to multiple dose administration. The magnitude of the effect was greater than the effect generally seen in longer term clinical trials, but this difference may be explained by the patient population in this study which was preselected for 'responsiveness' to an alpha1-adrenoceptor antagonist. These results support the utility of single dose uroflowmetric measurements in rapidly providing preliminary data on new investigational agents, specifically agents which act to increase urine flow in men with BPH. However, clinical efficacy would still need to be confirmed with longer term clinical trials. (+info)
Mechanisms of big endothelin-1-induced diuresis and natriuresis : role of ET(B) receptors.
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Endothelin-1 (ET-1) at high concentrations has marked antidiuretic and antinatriuretic activities, whereas its precursor, big endothelin-1 (big ET-1), has surprisingly potent diuretic and natriuretic actions. The mechanisms underlying the excretory effects of big ET-1 have not been fully elucidated. To explore these mechanisms, we examined the effects of a highly selective ET(B) antagonist (A-192621.1), a calcium channel blocker (verapamil), a nitric oxide synthase inhibitor (N-nitro-L-arginine methyl ester [L-NAME]), and a cyclooxygenase inhibitor (indomethacin) on the systemic and renal actions of big ET-1 in anesthetized rats. An intravenous bolus injection of incremental doses of big ET-1 (0.3, 1. 0, and 3.0 nmol/kg) produced a significant hypertensive effect that was dose dependent and prolonged (from 113+/-7 mm Hg to a maximum of 148+/-6 mm Hg). The administration of big ET-1 induced marked diuretic and natriuretic responses (urinary flow rate increased from 8.5+/-1 to 110+/-14 microL/min, and fractional excretion of sodium increased from 0.38+/-0.13% to 7.51+/-1.24%). Glomerular filtration rate and renal plasma flow significantly decreased only at the highest dose of big ET-1. Pretreatment with A-192621.1 (3 mg/kg plus 3 mg. kg(-1). h(-1)) significantly abolished the diuretic (17+/-5 microL/min to a maximum of 19+/-3 microL/min) and natriuretic (0. 29+/-0.1% to a maximum of 1.93+/-0.37%) responses induced by big ET-1. Moreover, A-192621.1 potentiated the decline in glomerular filtration rate and renal plasma flow and the increase in mean arterial blood pressure produced by the low doses of big ET-1. Similar to A-192621.1, pretreatment with a nitric oxide synthase inhibitor (L-NAME, 10 mg/kg plus 5 mg. kg(-1). h(-1)) significantly and comparably reduced the diuretic and natriuretic actions of big ET-1 and augmented the hypoperfusion/hypofiltration and systemic vasoconstriction induced by high doses of the peptide. Pretreatment with verapamil (2 mg. kg(-1). h(-1)) slightly inhibited the diuretic/natriuretic effects of the high-dose big ET-1 and completely prevented the increase in mean arterial blood pressure provoked by the peptide. Unlike verapamil and L-NAME, only indomethacin administration was associated with significant natriuretic/diuretic responses and did not influence the pressor effect and renal actions of big ET-1. Taken together, these results suggest that big ET-1-induced diuretic and natriuretic responses are mediated mainly by stimulation of nitric oxide production coupled to ET(B) receptor subtype activation. (+info)