The effect of changes in perfusion pressure on uteroplacental blood flow in the pregnant rabbit

The effect of perfusion pressure on uteroplacental blood flow was determined in pregnant rabbits utilizing the radioactive microsphere method. Control mean arterial pressure, 93 mm Hg +/- 2.6 SEM, was raised by carotid ligation to 109 +/- 4.1 mm Hg and then reduced with antihypertensive drugs to 74 +/- 1.3 mm Hg. Over this range of pressure there was no significant change in cardiac output, 605 +/- 36, 523 +/- 37, and 540 +/- 39 ml/min; or uteroplacental blood flow, 30 +/- 3.2, 27 +/- 5.2, and 29 +/- 4.5 ml/min, respectively. When prostaglandin synthesis was inhibited with either indomethacin or meclofenamate (2 mg/kg), uterine vascular resistance was higher but maintenance of uteroplacental flow occurred over a perfusion pressure of 89 +/- 6.7-115 +/- 9.3 mm Hg. With more severe hypotension induced with trimethaphan, control arterial pressure fell from 92 +/- 2.4 to 39 +/- 0.9 mm Hg, cardiac output fell from 514 +/- 17 to 407 +/- 22 ml/min (P less than 0.025) and uteroplacental blood flow fell from 6.1 +/- 0.9 to 2.5 +/- 0.9% of cardiac output (P less than 0.05), which represented an absolute fall from 32.4 +/- 5 to 10.6 +/- 3 ml/min (P less than 0.025). There was no significant change in renal blood flow expressed as percentage of cardiac output, 14.9 +/- 2 and 13 +/- 1.5%, or in absolute flow, 75 +/- 7.7 and 54 +/- 7 ml/min with trimethaphan-induced hypotension. These studies indicate that uteroplacental blood flow is maintained relatively constant over a range of perfusion pressure of 60-140 mm Hg in both normal and prostaglandin-inhibited pregnant rabbits. However, with reduction in pressure to 36-42 mm Hg, uteroplacental blood flow falls, expressed as a percentage of cardiac output and in absolute flow.     

The effects of a converting enzyme inhibitor (captopril) and angiotensin II on fetal renal function

1. Renal function was studied in chronically catheterized fetal sheep (119-128 days gestation), before and during treatment of the ewe with the angiotensin converting enzyme (ACE) inhibitor, captopril, which crosses the placenta and blocks the fetal renin angiotensin system. 2. An i.v. dose of 15 mg (about 319 micrograms kg-1) of captopril to salt-replete ewes followed by an infusion to the ewe of 6 mg h-1 (about 128 micrograms kg-1 h-1) caused a fall in fetal arterial pressure (P < 0.01), and a rise in fetal renal blood flow (RBF) from 67.9 +/- 5.6 to 84.9 +/- 8.3 ml min-1 (mean +/- s.e. mean) (P < 0.05). Renal vascular resistance and glomerular filtration rate (GFR) fell (P < 0.01); fetal urine flow (P < 0.01); fetal urine flow (P < 0.01) and sodium excretion declined (P < 0.05). 3. Ewes were treated for the next 2 days with 15 mg captopril twice daily. On the 4th day, 15 mg was given to the ewe and fetal renal function studied for 2 h during the infusion of captopril (6 mg h-1) to the ewe. Of the 9 surviving fetuses, 3 were anuric and 3 had low urine flow rates. When 6 micrograms kg-1 h-1 of angiotensin II was infused directly into the fetus RBF fell from 69 +/- 10.1 ml min-1 to 31 +/- 13.9 ml min-1, GFR rose (P < 0.05) and urine flow (P < 0.01) and sodium excretion increased in all fetuses. 4. It is concluded that the small fall in fetal arterial pressure partly contributed to the fall in fetal GFR but in addition, efferent arteriolar tone fell so that the filtration pressure fell further. Thus maintenance of fetal renal function depends on the integrity of the fetal renin angiotensin system. These findings explain why use of ACE inhibitors in human pregnancy is associated with neonatal anuria.     

Measurement of renal vein blood flow in rats by high-field magnetic resonance

The aim of the present study was to examine whether magnetic resonance imaging (MRI) based method for non-invasive in vivo measurement of vein blood flow in rats could be used to estimate renal blood flow (RBF). Measurements were performed using a high-field (7 Tesla) MRI scanner with a short echo time phase contrast velocity measurement pulse sequence. The method was evaluated in vitro by flow measurements in an acrylic pipe and in vivo by recording left renal vein blood flow in normal and unilaterally nephrectomized rats. In a subset of animals RBF was measured by a direct method using 14C-tetraethylammoniumbromide. In vitro a high accuracy was found between applied and MRI measured flow rates in the range from 0.5 to 33 ml/min (r = 0.997; P < 0.001). In vivo the MRI measured left renal vein blood flow was 70% higher in unilaterally nephrectomized animals compared to control animals (3.4 +/- 0.4 ml/min/ 100 g body wt vs. 2.0 +/- 0.1 ml/min/100 g body wt, P < 0.001). Direct measurements of RBF revealed comparable values (3.4 +/- 0.3 ml/min/100 g body wt vs. 2.3 +/- 0.4 ml/min/100 g body wt, P = 0.05). In addition, the left kidney volume was recorded by MRI with an increase amounting to 40% (1.18 +/- 0.05 ml vs. 0.84 +/- 0.02 ml; P < 0.001) in the nephrectomized group compared to controls. Finally, a positive correlation was seen between left renal vein blood flow and MRI measured renal volume (r = 0.91; P < 0.001). In summary, MRI is a non-invasive tool by which measurement of renal vein blood flow can be performed, and it is concluded that MRI-based renal vein flow measurements can be used to estimate RBF in small rodents.     

Effects of frequency of supplementation on dry matter intake and net portal and hepatic flux of nutrients in mature ewes that consume low-quality forage

Our objective was to determine the effects of frequency of soybean meal (SBM) supplementation on forage intake and net portal-drained viscera (PDV) and hepatic flux of nutrients in ewes that consume low-quality forage. Six Polled Dorset ewes (BW+/-SD = 82+/-9 kg) fitted with hepatic venous, hepatic portal, abdominal aortic, and mesenteric venous catheters were used in a replicated 3 x 3 Latin square design. Ewes consumed bromegrass hay (7.5% CP; DM basis). Treatments were no supplement (control), SBM fed once every 24 h, or SBM fed once every 72 h. In the SBM treatments, SBM was fed to provide 80 g/d of CP. Blood flow and net flux measurements were made on the 3rd d of each period so that ewes supplemented every 72 h were sampled the day of, the day after, and 2 d after supplementation. Arterial concentrations of alpha-amino N (AAN) and ammonia N were lower (P < .01) when SBM was fed, whereas arterial concentrations of urea N and oxygen were higher (P < .01). Feeding SBM increased net PDV release of AAN and ammonia N, net PDV removal of urea N, and oxygen consumption. A SBM x sampling day interaction (P < .05) occurred and resulted in greater net PDV absorption of AAN and ammonia N on the day after SBM supplementation when ewes were fed SBM on a 72-h interval. Net hepatic removal of AAN, ammonia N, and oxygen, and net hepatic release of urea N were greater (P < .01) with feeding SBM. The results indicate that the interval of SBM supplementation may affect the pattern of absorption without affecting the net absorption of nutrients.     

Experience of treatment for giant cell tumor of the upper tibia

Cell cycle analysis using flow cytometer (FCMX) was performed to evaluate the influence of cyclosporin A (CsA) on cellular proliferation during compensatory renal growth (CRG) in uninephrectomized (Ux) rats. CsA (50 mg/kg/day) was administered subcutaneously for 7 days and animals were scarificed 0, 12, 24, 48, 72, 120 and 168 h after Ux. The percent changes in the S (DNA synthesis) and G2M (DNA replication) phases in the contralateral kidney were analyzed. The cortical cells entering the S and G2M phases showed significant differences between CsA and vehicle groups (p = 0.0001, p = 0.001, respectively), but the medullary cells entering the S and G2M phases showed no significant differences between the 2 groups (p = 1.000, respectively). In the cortex, the CsA group showed a significant decrease in the S (at 12, 72 and 120 h) and G2M phases (at 24, 72 and 120 h) compared to the vehicle group (p < 0.05, respectively), but there was no significant difference in the medulla. In conclusion, cellular proliferation is suppressed in cortical cells by CsA.     

The renal factor in the post-traumatic "fluid overload" syndrome

Hypervolemia with hypertension often occurs 36-72 hours following massive blood and fluid replacement for hypovolemic shock. This syndrome of "fluid overload" has been attributed to the rapid intravascular flux of previously sequestered fluid in patients with impaired diuresis. This hypothesis was tested in 35 injured patients who received a mean of 9.3 L of blood and 17.4 L of salt during resucitation. The renal parameters measured soon after resuscitation included: 1) renal clearance of inulin (GFR), para-amino hippurate (ERPF), milliosmoles, sodium, and free water; 2) inulin space, renal vascular resistance (RVR), O2 consumption, renin, renal blood flow (RBF), and response to furosemide. Eighteen patients developed hypertension, hypervolemia, and respiratory insufficiency. When compared to the 17 normovolemic, non-hypertensive patients, the 18 hypervolemic patients had significantly increased RVR, with a significant decrease in RBF despite an increase in plasma volume and cardiac output. Furosemide produced less diuresis and natriuresis in the hypertensive patients. The balance between hypovolemia and "fluid overload" seemed percarious in the hypertensive patients. Peripheral renin and catecholamine levels were normal in both groups. Patients with post-traumatic "fluid overload" appear to have a combination of hypervolemia, respiratory insufficiency, hypertension, increased cardiac output, decreased extracellular fluid space, and decreased renal perfusion. These findings suggest that decreased interstitial fluid space compliance rather than "fluid overload" is the underlying factor leading to respiratory insufficiency. The therapeutic aspects of these findings are discussed.     

Net flux of glucose, lactate, volatile fatty acids, and nitrogen metabolites across the portal-drained viscera and liver of pregnant ewes

Our objective for this study was to determine the pattern of nutrient flux across the portal-drained viscera (PDV) and liver in ewes with varying numbers of fetuses. Catheters were placed in the hepatic portal vein, a branch of the hepatic vein, a mesenteric vein, and the abdominal aorta of ewes. Blood flow and net nutrient release across the PDV and liver were determined before exposure to rams. Ewes were then mated, which resulted in two ewes not pregnant and in six ewes with single and 11 ewes with twin lambs. Additional measurements were taken 103, 82, 61, 39, 19, and 6 d before parturition. Net PDV glucose release did not differ from zero (-.4 +/- 8.4 mmol/h; P = .58). In ewes with singles, premating net hepatic glucose release was 34.4 +/- 2.4 mmol/h, and 19 d before parturition it was 46.2 +/- 3.8 mmol/h. In ewes with twins, premating net hepatic glucose release was 36.8 +/- 2.7 mmol/h, and 19 d before parturition it was 47.4 +/- 2.8 mmol/h. Net PDV lactate release did not differ with litter size (P = .58) or days from parturition (P = .14; 9.7 +/- 4.6 mmol/h). Net lactate uptake by the liver increased in pregnant ewes as the pregnancy progressed (P < .001). The hepatic extraction ratio for lactate increased in late pregnancy (P = .02). Net PDV and hepatic release of acetate and propionate were not different with litter size or days from parturition. Hepatic extraction ratios of VFA did not differ with litter size or day from parturition. The patterns of change in hepatic metabolite fluxes are similar to the patterns of change in gravid uterus metabolite uptake. Hepatic lactate uptake seems to be regulated during pregnancy.     

Some genetic aspects of ovarian tumors

BACKGROUND: Propranolol and isosorbide-5-mononitrate (ISMN) are increasingly used in the prophylaxis of variceal haemorrhage in cirrhosis. However, recent studies have suggested that these drugs may compromise renal function, possibly by reducing renal blood flow. AIMS: To assess the acute effects of propranolol and ISMN on renal blood flow and other haemodynamic parameters in cirrhosis. PATIENTS AND METHODS: Twenty six cirrhotic patients were given either 80 mg propranolol, 20 mg ISMN, or a combination of the two drugs. Unilateral renal blood flow (RBF), azygos blood flow (AZBF), hepatic venous pressure gradient (HVPG), mean arterial pressure (MAP), and heart rate (HR) were recorded prior to and one hour after drug administration. RESULTS: Propranolol caused a reduction in HR (p < 0.005), AZBF (p < 0.01), and HVPG (p = 0.05), but no change in MAP or RBF (454.1 (77.3) versus 413.9 (60.3) ml/min). ISMN reduced MAP (p < 0.005) and HVPG (p < 0.01), but had no effect on HR, AZBF, or RBF (302.5 (49.4) versus 301.7 (58.8) ml/min). Combined treatment reduced MAP (p < 0.005), AZBF (p < 0.05), and HVPG (p = 0.002), but HR and RBF (419.2 (62.6) versus 415.1 (61.1) ml/min) remained unchanged. CONCLUSIONS: Despite the anticipated changes in other haemodynamic parameters, acute propranolol and/or ISMN administration did not reduce RBF. These drugs do not seem to compromise RBF in cirrhosis.     

Renal depressor mechanisms of physical training in patients with essential hypertension

To clarify characteristics of the patients in whom exercise training lowers blood pressure and to elucidate the mechanisms by which exercise training lowers blood pressure, we evaluated 24-h blood pressure, glomerular filtration rate (GFR), renal blood flow (RBF), filtration fraction (FF), plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma norepinephrine concentration (PNE), and incremental area of insulin/glucose (sigmaI/sigmaG) during 75 g oral glucose tolerance test, and assessed arterial baroreceptor function (BSI) before and after a 3-week exercise training program (four 6-min sessions daily at 75% VO2 max). Patients were classified as responders (n = 15) if they showed statistically significant reduction in the multiple comparison of 24-h mean arterial pressure (MAP), or as nonresponders (n = 15) if they did not. Although there were no significant differences between responders and nonresponders in age, weight, MAP, GFR, RBF, RPF, FF, PNE, sigmaI/sigmaG, or BSI before exercise, renal vascular resistance (RVR; P < .05), PRA (P < .05), and PAC (P < .05) were significantly higher in responders than in nonresponders. The fractional excretion of sodium (FENa) (P < .05) were significantly lower in responders than in nonresponders. After exercise training, FF (P < .01), RVR (P < .05), PNE (P < .05) PRA (P < .01), and sigmaI/sigmaG (P < .05) decreased significantly only in responders. The decrease in MAP significantly correlated with the reductions in FF (r = 0.46, P < .05), PNE (r = 0.52, P < .01) and RVR (r = 0.40, P < .05). Thus, in patients who have higher RVR and PRA, exercise training lowered blood pressure in parallel to a reduction in RVR associated with decreases in sympathetic tone and improvement of insulin resistance. Our results suggest that exercise-induced changes in renal hemodynamics may contribute to the reduction in blood pressure in these patients.     

Mechanisms of portal hypertension-induced alterations in renal hemodynamics, renal water excretion, and renin secretion

Clinical states with portal venous hypertension are frequently associated with impairment in renal hemodynamics and water excretion, as well as increased renin secretion. In the present investigation, portal venous pressure (PVP) was increased in anesthetized dogs undergoing a water diuresis. Renal arterial pressure was maintained constant in all studies. As PVP was increased from 6 to 20 mm Hg, decreases in cardiac output (2.5-2.0 liter/min, P less than 0.05) and mean arterial pressure (140-131 mm Hg, P less than 0.05) were observed. Increases in PVP were also associated with decreases in glomerular filtration rate (GFR, 40-31 ml/min, P less than 0.001), renal blood flow (RBF, 276-193 ml/min, P less than 0.001), and increases in renin secretion (232-939 U/min, P less than 0.025) in innervated kidneys. No significant change in either GFR or RBF and a decrease in renin secretion occurred with increases in PVP in denervated kidneys. To dissociate the changes in cardiac output and mean arterial pressure induced by increase PVP from the observed decreases in GFR and RBF, studies were performed on animals undergoing constriction of the thoracic inferior vena cava. In these studies, similar decreases in cardiac output and mean arterial pressure were not associated with significant changes in GFR or RBF. Increases in PVP also were associated with an antidiuresis as urine osmolality increased from 101 to 446 mosmol/kg H2O (P less than 0.001). This antidiuresis was significantly blunted but not abolished by acute hypophysectomy. In hypophysectomized animals, changes in free water clearance and urine flow were linearly correlated as PVP was increased. These studies indicate that increases in PVP result in decreases in GFR and RBF and increases in renin secretion mediated by increased renal adrenergic tone. Increased PVP is also associated with antidiuresis; this antidiuresis is mediated both by vasopressin release and by diminished tubular fluid delivery to the distal nephron.     

Influence of nitric oxide in the chronic phase of two-kidney, one clip renovascular hypertension

Chronic two-kidney, one clip (2K1C) renovascular hypertension is characterized by a largely angiotensin-independent elevated blood pressure (BP). We hypothesized that the long-term effect of hypertension would compromise endothelium-derived nitric oxide (NO) and diminish its influence in controlling renal perfusion. We determined the influence of endothelium-derived NO on renal hemodynamics and the angiotensin-NO interaction regulation of renal perfusion in rats with chronic 2K1C hypertension. Renal blood flow (RBF) was measured by radioactive microspheres in rats with either early-phase (4 weeks after clipping, n=7) or chronic-phase (13 to 16 weeks after clipping, n=7) 2K1C hypertension. The systemic and renal response to NO synthesis inhibition was determined with 10 mg/kg body wt N omega-nitro-L-arginine methyl ester (L-NAME). In rats with early-phase 2K1C hypertension, BP was 149+/-3 mm Hg, which increased by 42+/-3 mm Hg with L-NAME (P<.001). L-NAME decreased RBF by 20% (P<.02) and 17% (P<.005) and increased renal vascular resistance (RVR) by 58% (P<.005) and 62% (P<.02) in the nonclipped and clipped kidneys, respectively. In rats with chronic 2K1C hypertension, BP was 166+/-3 mm Hg, and L-NAME increased this by 35+/-6 mm Hg (P<.001). In the nonclipped and clipped kidneys of chronic 2K1C hypertensive rats, L-NAME decreased RBF by 20% (P<.01) and 17% (P<.01) and increased RVR by 51% (P<.005) and 60% (P<.02), respectively. There were no differences in L-NAME-induced changes between early- and chronic-phase 2K1C hypertensive rats. Next, we treated seven chronic-phase 2K1C hypertensive rats with 10 mg/kg body wt losartan, which reduced BP by only 7.7% (P<.005). After losartan, L-NAME increased BP by 41+/-3 mm Hg (P<.001), decreased RBF to the nonclipped kidney by 44% (P<.05), and increased RVR by 110% (P<.005); the decrease in RBF was significantly greater compared with untreated chronic-phase controls (P<.05). In the clipped kidney, L-NAME decreased RBF by 26% (P<.05) and increased RVR by 76% (P <.05). Thus, angiotensin blockade did not attenuate the systemic or renal vasoconstriction to L-NAME. Our results suggest that in both early and chronic phases of 2K1C hypertension, NO contributes significant dilator tone to buffer the hypertension and maintains perfusion of both kidneys by counterbalancing angiotensin-independent vasoconstriction.     

Spontaneous resolution of p58/EB6 antigen restricted NK-type lymphoproliferative disease of granular lymphocytes: role of Epstein Barr virus infection

OBJECTIVE: This study compared late-pregnant radial uterine arteries that supplied the placenta versus the myoendometrium to evaluate differences in active and passive mechanical properties. STUDY DESIGN: Pressurized segments of placental versus myoendometrial radial uterine arteries from late-pregnant (day 28 to 30) New Zealand White rabbits (n = 12) were compared in vitro for differences in luminal diameter, wall thickness, distensibility, and intrinsic tone as a function of transmural pressure. RESULTS: Both types of arteries responded to increased transmural pressure with active vasoconstriction; however, the amount of tone present in myoendometrial arteries was significantly greater than in placental arteries (percent tone at 75 mm Hg = 39% +/- 3% for myoendometrial versus 31% +/- 2% for placental arteries, p < 0.01). Measurements of unpressurized, fully relaxed arteries revealed that placental arteries were 38% larger in diameter and had thicker walls than myoendometrial arteries did. However, myoendometrial arteries were significantly more distensible at transmural pressures >5 mm Hg. CONCLUSIONS: The increased size and diminished tone of placental compared with adjacent myoendometrial arteries would favor increased blood flow to the placenta; differences in size and passive mechanical properties suggest that a localized factor(s) originating from the fetus or placenta contributes to the gestational enlargement of those arteries that perfuse the placenta.     

Intrarenal haemodynamics and renal dysfunction in endotoxaemia: effects of nitric oxide synthase inhibition

1. This study investigated the effects of low dose endotoxin (lipopolysaccharide, LPS) on (i) systemic haemodynamics, (ii) renal blood flow (RBF), (iii) renal cortical and medullary perfusion and (iv) renal function in the anaesthetized rat. We have also investigated the effects of nitric oxide (NO) synthase (NOS) inhibition with NG-methyl-L-arginine (L-NMMA) on the alterations in systemic and renal haemodynamics and renal function caused by endotoxin. 2. Infusion of low dose LPS (1 mg kg-1 over 30 min, n = 6) caused a late fall in mean arterial blood pressure (MAP, at 5 and 6 h after LPS), but did not cause an early (at 1-4 h after LPS) hypotension. The pressor effect of noradrenaline (NA, 1 microgram kg-1, i.v.) was significantly reduced at 1 to 6 h after LPS (vascular hyporeactivity). Infusion of L-NMMA (50 micrograms kg-1 min-1 commencing 60 min before LPS and continued throughout the experiment, n = 7) abolished the delayed hypotension and significantly attenuated the vascular hyporeactivity to NA (at 2-6 h). 3. Infusion of LPS (1 mg kg-1 over 30 min, n = 6) caused a rapid (within 2 h) decline in renal function (measured by inulin clearance) in the absence of a significant fall in MAP or renal blood flow (RBF). L-NMMA (n = 7) attenuated the impairment in renal function caused by LPS so that the inulin clearance in LPS-rats treated with L-NMMA was significantly greater than in LPS-rats treated with vehicle (control) at 3-6 h after infusion of LPS. 4. Endotoxaemia also caused a significant reduction in renal cortical, but not medullary perfusion (measured as Laser Doppler flux). Infusion of L-NMMA caused a significant further fall in cortical perfusion and a significant fall in medullary perfusion in the absence of changes in RBF. 5. Infusion of LPS resulted in a progressive increase in the plasma levels of nitrite/nitrate (an indicator of the formation of NO), so that the plasma concentration of nitrite/nitrate was significantly higher than baseline at 150 to 330 min after LPS. Infusion of L-NMMA attenuated the rise in the plasma concentration of nitrite/nitrate (at 270 and 330 min, P < 0.05) caused by LPS. 6. Thus, the renal dysfunction caused by injection of low dose of endotoxin in the rat occurs in the absence of significant falls in blood pressure or total renal blood flow. Inhibition of NOS activity with L-NMMA attenuates the renal dysfunction caused by endotoxin (without improving intrarenal haemodynamics), suggesting that an overproduction of NO may contribute to the development of renal injury and dysfunction by causing direct cytotoxic effects.     

Uterine pressure-flow relationships during early gestation

Placental and myoendometrial pressure-flow relationships were determined in 17 gravid ewes between 29 and 110 gestational days with the use of radioactive-labeled microsphere injections under flow meter guidance. Myoendometrial relationships were consistently curvilinear with convexity toward the flow axis. From 29 to 40 days, caruncular-cotyledonary relationships were similar to myoendometrial ones. After 50 days, the relationship was slightly but significantly curvilinear with convexity toward the pressure axis. From 42 to 50 days, responses were intermediate. The changes in caruncle-cotyledon vascular reactivity correlated with the onset and maturation of interdigitation of fetal and maternal tissues during definitive placentation. A hypothesis for these changes in vascular reactivity is presented.     

Renal effects of oral prostaglandin supplementation after ibuprofen in diabetic subjects: a double-blind, placebo-controlled, multicenter trial

Prostaglandins of the E series (PGE) are known to contribute to the maintenance of renal hemodynamics in subjects with chronic renal insufficiency. Agents that block PGE synthesis, nonsteroidal anti-inflammatory agents (NSAID), are widely used by people with renal insufficiency. This study was undertaken in subjects with renal insufficiency secondary to diabetes to evaluate the acute effects of a PGE1 analog, misoprostol, on NSAID-induced changes in RBF, as calculated by para-aminohippurate clearance, and GFR, as calculated by inulin clearance. Sodium excretion was also assessed. Twenty-five fasting subjects with a mean age of 56 +/- 4 yr received 800 mg of ibuprofen orally. A concomitant dose of either a placebo (PL) or 200 micrograms of misoprostol was also given. This was followed in 1 h by either a placebo or an additional 200-micrograms dose of misoprostol. Measurements for the determination of RBF, GFR, blood pressure, and fractional excretion of sodium were performed every 30 min for the next 5 h. The greatest reduction in both GFR (-25 +/- 7 mL/min per 1.73 m2 PL versus -10 +/- 4 mL/min per 1.73 m2, misoprostol delta GFR; P < 0.05) and RBF (-48 +/- 21 mL/min per 1.73 m2 PL versus -15 +/- 8 mL/min per 1.73 m2, M delta RBF; P < 0.05) occurred approximately 2 h after the NSAID dose. No significant differences were noted in blood pressure, fractional excretion of sodium, or other measured parameters between groups during the entire study. Gastrointestinal upset was the most common side effect observed in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in plasma endothelin-1 and lipid peroxidate levels and amount of superoxidate dismutase in red blood cell in patients with pregnancy-induced hypertension

OBJECTIVE: To evaluate the role of endothelin (ET-1) and lipid peroxide (LPO) in the pathogenesis of pregnancy-induced hypertension (PIH). METHODS: The plasma concentrations of ET-1, LPO and the amount of superoxide dismutase (SOD) in red blood cell were measured by radioimmunoassay, thiobarbituric acid fluorimetric determination and catechol self-oxidation determination respectively in total 95 women (normal non-pregnant women 15, Late pregnant women 20 and patients with PIH 60). RESULTS: (1) The levels of ET-1, LPO and SOD in normal late pregnant women were significantly higher than those in non-pregnant women (P < 0.01), but the LPO/SOD ratio was not significantly different between the two groups. (2) The levels of plasma ET-1 and LPO/SOD ratio in cases with PIH were markedly higher than those in normal late pregnant women, and it increased with the severity of the disease and returned to the levels of normal late pregnant women within 3-7 days after delivery. (3) There was a positive correlation between ET-1 and LPO/SOD ratio in PIH. CONCLUSIONS: The imbalance of oxidation and antioxidation and endothelial cell injury may play an important role in the pathogenesis of PIH.     

Maternal renal artery blood flow velocimetry in normal and hypertensive pregnancies

OBJECTIVE: To investigate the effect of normal pregnancy and hypertensive disorders of pregnancy on the maternal renal artery Doppler blood flow velocity indices. METHODS: The patient material consisted of 30 normal pregnant women, 29 women with pregnancy induced hypertension, 43 women with preeclampsia and 22 pregnant women with chronic hypertension. Blood flow velocities in the segmental renal arteries from the right kidney were analysed by pulsed and color Doppler. The systolic/diastolic (s.d.) ratio, resistance index (RI) and pulsatility index (PI) were used for Doppler waveform analysis. RESULTS: In all of the groups of hypertensive pregnant women renal artery Doppler indices were significantly lower compared to the normal pregnant women group. There was a significant negative relationship between renal artery PI and mean arterial pressure in the preeclampsia group and in the chronic hypertension group. CONCLUSION: The present results demonstrate that the mechanism of renal autoregulation in preeclampsia might be altered, leaving glomerulus unprotected from increased blood pressure. It seems that the concept of renal vasoconstriction in preeclampsia might be disputed and needs further investigation.     

Acute effects of transjugular intrahepatic portosystemic stent-shunt (TIPSS) procedure on renal blood flow and cardiopulmonary hemodynamics in cirrhosis

OBJECTIVE: An acute increase in portal pressure is associated with an immediate reduction in renal blood flow. It has been suggested that this supports the presence of an hepatorenal reflex. In this study, we used TIPSS placement as a model to investigate the effect of an acute reduction in portal pressure on renal blood flow and cardiopulmonary hemodynamic parameters. METHODS: Eleven cirrhotic patients were studied during elective TIPSS placement for variceal hemorrhage (n = 9) or refractory ascites (n = 2). Unilateral renal blood flow (RBF) was measured before and at 5, 15, 30, 45, and 60 min after shunt insertion. Heart rate (HR), mean arterial pressure (MAP), right atrial pressure (RAP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and systemic vascular resistance (SVR) were also measured before and 30 min after TIPSS placement. RESULTS: Despite significant increases in CO (p = 0.001), RAP (p < 0.001), PAP (p < 0.001), and PCWP (p = 0.001), and a fall in SVR (p = 0.003), no change was observed in RBF, HR, or MAP after TIPSS placement. The fall in the portoatrial pressure gradient correlated only with the rise in CO (p < 0.05) and the drop in SVR (p < 0.05). CONCLUSION: Despite the fall in portal pressure and the systemic hemodynamic changes caused by TIPSS placement, there is no immediate effect on RBF. Any improvement in renal function after TIPSS procedure does not appear to be due to an acute increase in RBF.     

Alteration of renal blood flow during epidural anesthesia in normal subjects

The cardiovascular consequences of epidural anesthesia secondary to sympathetic blockade are well documented; however, their repercussions on renal hemodynamics in humans have not been reported. We investigated the effect of epidural anesthesia on renal blood flow (RBF) in 13 healthy volunteers 18-45 yr of age. RBF was measured using paraaminohippurate clearance before and after bilateral T6 epidural sensory block (to ensure adequate sympathetic renal nerve blockade). Epidural anesthesia was established using 22 +/- 3 mL of 2% plain lidocaine (without epinephrine) via L1-L2 epidural catheter; urine output was measured using a three-way Foley catheter. Mean arterial pressure remained > or = 70 mm Hg in all subjects without any pharmacologic intervention. Mean RBF before epidural anesthesia was 16.1 +/- 6.8 mL.kg-1.min-1 and 14.3 +/- 2.9 mL.kg-1.min-1 after bilateral T6 epidural blockade. We conclude that the institution of epidural anesthesia in healthy subjects does not result in a significant change in RBF (P > 0.25).     

Pregnancy increases soluble and particulate guanylate cyclases and decreases the clearance receptor of natriuretic peptides in ovine uterine, but not systemic, arteries

Pregnancy increases uterine blood flow by 30- to 50-fold and uterine production of cGMP by 38-fold. Moreover, cGMP causes potent vasodilatation. We hypothesized that pregnancy up-regulates soluble and particulate guanylate cyclases (sGC and pGC) in ovine uterine arteries. Activities of sGC and pGC were compared by measuring cGMP production (37 C; 10 min) by uterine arteries from nonpregnant (n = 5) and pregnant (n = 4, 120 +/- 2 days' gestation; term = 145 +/- 3 days; mean +/- SE) ewes after sodium nitroprusside (100 microM), atrial natriuretic peptide (1 microM), or C-type natriuretic peptide (CNP; 1 microM) treatment. The protein and/or messenger RNA expressions of sGC beta1-subunit, pGC-A, pGC-B, the clearance receptor of natriuretic peptide (CR), and CNP were investigated in uterine and systemic (renal and/or omental) arteries from nonpregnant (n = 29) and pregnant (n = 21; 125 +/- 2 days' gestation) ewes. The potencies of uterine arterial GC activities were sGC > pGC-A > pGC-B. Activities as well as protein expression of sGC, pGC-A, and pGC-B in pregnant uterine arteries were increased 48-128% above those in nonpregnant controls concomitant with a 34% down-regulation of CR protein expression; systemic arterial protein expressions were unaltered. These changes in uterine arterial GC-B and CR were confirmed using RT-PCR. Immunohistochemical staining of CNP in uterine, but not systemic, arterial endothelium from pregnant ewes was much stronger than that from nonpregnant ewes. Thus, two distinct GC pathways are present in ovine uterine artery, and both may be specifically upregulated during pregnancy and so contribute to the tremendous local increase in cGMP production during pregnancy.