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W Jiménez

Publications and source records attributed to W Jiménez.

At least 19 recordsLinked to original sources
PubMed2005

Increased anandamide induced relaxation in mesenteric arteries of cirrhotic rats: role of cannabinoid and vanilloid receptors.

BACKGROUND AND AIMS: Anandamide is an endocannabinoid that evokes hypotension by interaction with peripheral cannabinoid CB1 receptors and with the perivascular transient receptor potential vanilloid type 1 protein (TRPV1). As anandamide has been implicated in the vasodilated state in advanced cirrhosis, the study investigated whether the mesenteric bed from cirrhotic rats has an altered and selective vasodilator response to anandamide. METHODS: We assessed vascular sensitivity to anandamide, mRNA and protein expression of cannabinoid CB1 receptor and TRPV1 receptor, and the topographical distribution of cannabinoid CB1 receptors in resistance mesenteric arteries of cirrhotic and control rats. RESULTS: Mesenteric vessels of cirrhotic animals displayed greater sensitivity to anandamide than control vessels. This vasodilator response was reverted by CB1 or TRPV1 receptor blockade, but not after endothelium denudation or nitric oxide inhibition. Anandamide had no effect on distal femoral arteries. CB1 and TRPV1 receptor protein was higher in cirrhotic than in control vessels. Neither CB1 mRNA nor protein was detected in femoral arteries. Immunochemistry showed that CB1 receptors were mainly in the adventitia and in the endothelial monolayer, with higher expression observed in vessels of cirrhotic rats than in controls. CONCLUSIONS: These results indicate that anandamide is a selective splanchnic vasodilator in cirrhosis which predominantly acts via interaction with two different types of receptors, CB1 and TRPV1 receptors, which are mainly located in perivascular sensory nerve terminals of the mesenteric resistance arteries of these animals.

Animals↗
PubMed2003

Expired nitric oxide in the newborn with high risk of perinatal infection.

The objective of this study is to determine expired nitric oxide (expNO) in the first 3 days of life in relation to: hours of life, gestational age, type of labor, and risk of perinatal infection. Our hypothesis has been that expNO increases in newborns with high risk of perinatal infection. Total expNO was measured in 166 newborns: 108 healthy (63 full-term and 45 preterm), 30 with low risk of perinatal infection, and 28 with high risk of perinatal infection treated with antibiotics but without positive hemoculture. Expired gas was collected using a face mask and NO concentration was determined by chemiluminescence. Total expNO neither correlated with gestational age, birth weight or serum NOx, nor changed after cesarean section, but was related to hours of life. Total expNO in the < or = 36-hour subgroups (median, interquartile range) was higher in the high-risk perinatal infection newborns ( n = 8; 5.33 (4.5-7.2) nL/min*Kg) than in healthy newborns ( n = 59; 4.13 (3.5-4.7) nL/min*kg) or low-risk perinatal infection newborns ( n = 18; 3.99 (3.4-4.7) nL/min*kg). In the 37 to 72-hour subgroups there were also differences between healthy newborns ( n = 49; 4.68 (4.1-5.3) nL/min*kg) or low-risk perinatal infection newborns on the one hand ( n = 12, 4.55 (3.9-5.2) nL/min*kg) and high risk perinatal infection newborns on the other ( n = 20; 9.69 (7.6-11.1) nL/min*kg). Then, total expNO increased in newborns with high risk of perinatal infection, regardless of hours of life.

Bacterial Infections↗
PubMed2003

Plasma nitrite/nitrate and endothelin-1 concentrations in neonatal sepsis.

AIM: To determine the changes in plasma nitrite/nitrate (NOx) and endothelin-1 (ET-1) concentrations during neonatal sepsis. METHODS: In a prospective study, 60 consecutive newborns meeting the criteria for sepsis and without receiving exogenous nitric oxide (25 haemoculture-positive [HC+] and 35 haemoculture-negative [HC-]) were compared with 68 healthy newborns (46 full-term and 22 preterm). NOx and ET-1 concentrations were measured in each newborn within 48 h of diagnosis of sepsis and then every third day up to three determinations. SNAP-II and SNAPPE-II severity scores were performed at the moment of highest clinical severity. RESULTS: At the beginning of the sepsis period, controls and septicaemic newborns had similar NOx and ET-1 levels, with the exception of infants with severe HC+ sepsis. Throughout the sepsis period, NOx increased in moderate HC+ sepsis and decreased in HC--sepsis, reaching a significant difference at the end of the study period (59.9 +/- 72.7 vs 33.9 15.3 micromol/L; p = 0.036). Meanwhile, ET-1 in newborns with severe HC+ sepsis remained higher than that in the moderate HC+ sepsis group and HC--group, reaching significant differences in all the periods. The highest ET-1 value was positively correlated with SNAP-II and SNAPPE-II scores. CONCLUSION: NOx concentrations increased throughout the neonatal HC+ sepsis period, reaching significant differences after 7-9 d. The highest ET-1 levels in neonatal HC+ sepsis emerged before the NOx peak, at 3-5 d, and later decreased. Only newborns with severe HC+ sepsis presented a significant increase in ET-1 concentrations from the beginning of the septicaemic process.

Birth Weight↗
PubMed2001

A prognostic model for predicting survival in cirrhosis with ascites.

BACKGROUND/AIMS: Parameters evaluating renal function and systemic hemodynamics are of prognostic significance in cirrhosis with ascites but are rarely used in the evaluation of survival of these patients. The aim of the current study was to develop a prognostic model to estimate survival of patients with cirrhosis and ascites. METHODS: 216 Cirrhotic patients admitted to hospital for the treatment of ascites were evaluated. Thirty-two demographic, clinical and laboratory variables, including parameters assessing liver and renal function and systemic hemodynamics, were analyzed as predictive factors of survival by using a Cox regression model. RESULTS: Four variables had independent prognostic value: renal water excretion, as assessed by measuring diuresis after water load, mean arterial pressure, Child-Pugh class, and serum creatinine. According to these features a prognostic index was calculated that allows to estimate survival in patients with cirrhosis and ascites. The model accurately predicted survival in an independent series of 84 patients with cirrhosis and ascites. CONCLUSION: A prognostic model that uses four easily available variables and predicts prognosis in cirrhotic patients with ascites has been developed. This model may be useful in the evaluation of patients with ascites for liver transplantation.

Ascites↗
PubMed2001

Human hepatic stellate cells secrete adrenomedullin: potential autocrine factor in the regulation of cell contractility.

BACKGROUND/AIMS: Hepatic stellate cells (HSCs) are perisinusoidal pericytes which have receptors for vasoactive factors, such as endothelin-1, which can regulate cell contractility in an autocrine manner. It is unknown whether human HSCs have receptors for and are able to synthesize the vasodilator peptide adrenomedullin (ADM), a peptide produced by most contractile cells. METHODS AND RESULTS: Stimulation of HSCs with ADM resulted in a dose-dependent raise in cAMP concentration (radioimmunoassay) and markedly blunted the endothelin-induced increase in [Ca2+]i and cell contraction, as assessed in cells loaded with fura-2 using a morphometric method. The existence of the receptor CRLR for ADM and their associated proteins RAMP-1 and RAMP-2 was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, activated human HSCs spontaneously secreted ADM in the culture medium in a time-dependent manner. ADM secretion was markedly enhanced by tumour necrosis factor-alpha and interleukin-1beta. Specific mRNA for ADM (RT-PCR and Northern blot) was detected in HSCs and increased after incubation of cells with cytokines. CONCLUSIONS: Human HSCs have functional receptors for ADM, the stimulation of which blunts the contractile effect of endothelin-1. Cultured human HSCs secrete ADM in baseline conditions. This secretion is markedly increased by cytokines. These results suggest that ADM can regulate HSCs' contractility in an autocrine manner.

Adrenomedullin↗
PubMed2001

[Estradiol enhances endothelium-dependent vasodilation via a nitric oxide pathway].

BACKGROUND AND AIM: The mechanisms by which estradiol dilates arterial vessels are still unclear. Our aim was to study if estradiol enhances endothelium-dependent vasodilation in an experimental model of human arteries in vitro, and if this effect is nitric oxide mediated. METHODS: Using organ bath chambers, we studied 18 arterial rings obtained from left internal mammary arteries during coronary artery bypass grafting surgery. Response to acetylcholine was evaluated at baseline and after the addition of estradiol 10-6 mol/l to the medium, both in the presence or absence of a nitric oxide synthase inhibitor (L-NNA 10-4 mol/l). RESULTS: Estradiol significantly enhanced the relaxation of the arterial rings in response to acetylcholine (52 +/- 20% after estradiol versus 42 +/- 22% at baseline; n = 10; p = 0.02). However, endothelium-dependent vasodilation relaxation after estradiol addition was not enhanced in the presence of L-NNA (47 +/- 25% after estradiol versus 38 +/- 22% at baseline; n = 8; p = NS). CONCLUSIONS: Estradiol in vitro enhances endothelium-dependent vasodilation of internal human mammary artery rings; this effect is blunted after the addition to the medium of a nitric oxide inhibitor. Therefore, the vasodilator properties of estradiol at the studied dosage depend on the nitric oxide pathway.

Aged↗
PubMed2001

Increased production of vascular endothelial growth factor in peritoneal macrophages of cirrhotic patients with spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis (SBP) is a common complication of cirrhotic patients with ascites that usually results in renal failure and death despite the efficacy of the current antibiotic therapy. The pathogenesis of these phenomena is poorly known but it has been related to the production of vasoactive cell mediators locally acting on the splanchnic vasculature. Because previous studies showed that peritoneal macrophages of cirrhotic patients may produce high quantities of vascular endothelial growth factor (VEGF), a powerful vessel permeabilizing agent, when stimulated by cytokines and bacterial lipopolysaccharide, the present study was aimed to seek whether peritoneal macrophages of SBP patients are induced to produce increased amounts of VEGF. Our results indicate that the production rate and the messenger RNA (mRNA) and protein expression of this substance are increased in macrophages of patients with SBP in comparison with those of noninfected cirrhotic patients. This characteristic feature is absent in circulating monocytes of these patients. Moreover, enhanced endothelial cell proliferation induced by conditioned medium of macrophages isolated from the ascites of patients with SBP is abolished by anti-VEGF antibody, and peritoneal tissue of cirrhotic patients expresses both VEGF receptors, Flt-1 and KDR. These results, therefore, are consistent with the concept that locally released macrophage-derived VEGF may result in increased vascular permeability and plasma leakage in the peritoneal vessels of cirrhotic patients with SBP.

Bacterial Infections↗
PubMed2001

Effect of salt intake on endothelium-derived factors in a group of patients with essential hypertension.

The aim of the present study was to evaluate the effects of the level of salt intake on endothelium-derived factors in a group of patients with essential hypertension. A group of 50 patients with essential hypertension who had never been treated for the condition were placed on a low-sodium (50 mmol/day), low-nitrate (400 micromol/day) diet, which was supplemented, in a single-blind fashion, with placebo tablets for the first 7 days and then with NaCl tablets (200 mmol/day) for a further 7 days (total sodium intake 250 mmol/day). At the end of both periods, 24-h ambulatory blood pressure monitoring was performed. In addition, plasma levels and 24-h urinary excretion of nitrites plus nitrates and cGMP were measured, along with plasma levels of endothelin. A high salt intake promoted significant decreases in plasma levels of nitrites plus nitrates (from 41.0+/-2.1 to 32.8+/-1.8 nmol/ml; P<0.001), 24-h urinary nitrate excretion (from 417+/-36 to 334+/-37 micromol/24 h; P=0.045) and plasma endothelin levels (from 5.6+/-0.3 to 4.6+/-0.3 pg/ml; P=0.007). The plasma concentration and 24-h urinary excretion of cGMP were not altered significantly by a high salt intake. We did not find any relationship between endothelium-derived products and 24-h mean blood pressure, at either low or high salt intakes, or between changes induced by the high-salt diet. A high salt intake also induced significant decreases in plasma renin activity, angiotensin II and aldosterone, and a significant increase in atrial natriuretic peptide. We conclude that a high salt intake decreases the plasma concentration and urinary excretion of nitrates and plasma levels of endothelin in patients with essential hypertension, suggesting that the level of salt intake may affect endothelial cell function. However, these alterations are not correlated with changes in blood pressure induced by the high salt intake.

Adult↗
PubMed2000

Increased activity of guanosine 3'-5'-cyclic monophosphate phosphodiesterase in the renal tissue of cirrhotic rats with ascites.

A possible defect of guanosine 3'-5'-cyclic monophosphate (cGMP) content in the renal tissue caused by an increased activity of cGMP phosphodiesterase (PDE) has, so far, not been evaluated in the pathogenesis of renal resistance to endogenous natriuretic peptides (ENP) in cirrhosis with ascites. To test this hypothesis the activity of cGMP-PDE and the concentration of cGMP were evaluated in vitro in the renal tissue of 10 control rats and 10 cirrhotic rats with ascites before and after the intravenous (IV) administration of Zaprinast (Sigma, St. Louis, MO), a specific cGMP-PDE inhibitor (30 microgram/kg/min). Moreover, the effects of the intravenous administration of Zaprinast (15 microgram/kg/min and 30 microgram/kg/min) on renal plasma flow (RPF), glomerular filtration rate (GFR), and urinary sodium excretion (U(Na)V) were evaluated in 10 conscious control rats and 10 conscious cirrhotic rats with ascites. The effects of Zaprinast on plasma renin activity (PRA) was also evaluated in 10 control rats and in 10 cirrhotic rats with ascites. Finally, the effect of Zaprinast on RPF, GFR, and U(Na)V were evaluated in 10 cirrhotic rats after the IV administration of the ENP-receptor antagonist, HS-142-1. The renal content of cGMP was reduced in cirrhotic rats because of increased activity of cGMP-PDE. Zaprinast inhibited cGMP-PDE activity and increased the renal content of cGMP in these animals. The inhibition of cGMP-PDE was associated with an increase in RPF, GFR, and U(Na)V and a reduction in PRA. HS-142-1 prevented any renal effect of Zaprinast in cirrhotic rats. In conclusion, an increased activity of the cGMP-PDE in renal tissue contributes to the renal resistance to ENP in cirrhosis with ascites.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome.

BACKGROUND/AIM: Ornipressin, a vasopressin analog with potent splanchnic vasoconstrictor action, has been shown to reverse hepatorenal syndrome. However, its usefulness in clinical practice is limited by frequent ischemic complications. The aim of this study was to assess the efficacy of terlipressin, an analog of vasopressin with a low profile of side effects, plus albumin in this condition. METHODS: Nine consecutive patients with cirrhosis and hepatorenal syndrome were included in a pilot study of terlipressin (0.5-2 mg/4 h i.v.) therapy associated with iv albumin. RESULTS: Treatment (9 days, range 5-15) was associated with a marked reduction of serum creatinine (3.9+/-0.7 to 1.3+/-0.1 mg/dl, p<0.001, mean+/-SE). Reversal of hepatorenal syndrome (reduction of creatinine below 1.5 mg/dl) was observed in seven of the nine patients. There was a remarkable improvement in circulatory function, with an increase in mean arterial pressure (68+/-2 to 80+/-4 mmHg, p<0.05) and suppression of vasoconstrictor systems activity (plasma renin activity and plasma norepinephrine decreased from 23+/-12 ng/ml x h and 1549+/-373 pg/ml to 3.5+/-2 ng/ml x h and 373+/-98 pg/ml, respectively, p<0.01 for both). No patient developed signs of intestinal, myocardial or distal ischemia. CONCLUSIONS: Terlipressin associated with albumin appears to be a safe and effective treatment of hepatorenal syndrome.

Adult↗
PubMed2000

Complications of cirrhosis. II. Renal and circulatory dysfunction. Lights and shadows in an important clinical problem.

The pathophysiology of circulatory and renal dysfunction in cirrhosis and the treatment of ascites and related conditions (hepatorenal syndrome and spontaneous bacterial peritonitis) have been research topics of major interest during the last two decades. However, many aspects of these problem remain unclear and will constitute major areas of investigation in the next millennium. The pathogenesis of sodium retention, the most prevalent renal function abnormality of cirrhosis, is only partially known. In approximately one third of patients with ascites, sodium retention occurs despite normal activity of the renin-aldosterone and sympathetic nervous systems and increased circulating plasma levels of natriuretic peptides and activity of the so-called natriuretic hormone. These patients present an impairment in circulatory function which, although less intense, is similar to that of patients with increased activity of the renin-aldosterone and sympathetic nervous systems, suggesting that antinatriuretic factors more sensitive to changes in circulatory function that these systems may be important in the pathogenesis of sodium retention in cirrhosis. The development of drugs that inhibit the tubular effect of antidiuretic hormone and increase renal water excretion without affecting urine solute excretion has opened a field of great interest for the management of water retention and dilutional hyponatremia in cirrhosis. Two families of drugs, the V2 vasopressin receptor antagonists and the kappa-opioid agonists, have been shown to improve free water clearance and correct dilutional hyponatremia in human and experimental cirrhosis with ascites. The first type of drugs blocks the tubular effect of antidiuretic hormone and the second inhibits antidiuretic hormone secretion by the neurohypophysis. On the other hand, two new treatments have also been proved to reverse hepatorenal syndrome in cirrhosis. The most interesting one is that based on the simultaneous administration of plasma volume expansion and vasoconstrictors. The second is transjugular intrahepatic porto-systemic shunt. The long-term administration (1-3 weeks) of analogs of vasopressin (ornipressin or terlipressin) or other vasoconstrictors together with plasma volume expansion with albumin is associated with a dramatic improvement in circulatory function and normalization of serum creatinine concentration in patients with severe hepatorenal syndrome. Of interest is the observation that in many of these patients, hepatorenal syndrome does not recur following discontinuation of the treatment, thus raising important questions about the mechanism by which hepatorenal syndrome follows a progressive course in most untreated cases. The pathogenesis of circulatory dysfunction in cirrhosis and the role of local mechanisms in the development of the splanchnic arteriolar vasodilation associated with portal hypertension will continue as important topics in clinical and basic research in Hepatology. Of special interest is the study of the mechanism by which circulatory function further deteriorates following complications such as severe bacterial infection or therapeutic interventions such as therapeutic paracentesis, and the adverse consequences of the impairment in circulatory function on renal and hepatic hemodynamics. Finally, although major advances have been made concerning the treatment and secondary prophylaxis of spontaneous bacterial peritonitis in cirrhosis, many aspects of the pathogenesis of this infection remain unclear. The mechanism of bacterial translocation and of the colonization of bacteria in the ascitic fluid are particularly important to design adequate measures for primary prophylaxis of this severe bacterial infection.

Animals↗
PubMed2000

Nitric oxide synthase II mRNA expression in cardiac tissue of patients with heart failure undergoing cardiac transplantation.

OBJECTIVES: To examine whether inducible nitric oxide synthase is expressed in myocardial tissue of patients with heart failure. BACKGROUND: There is increasing evidence that alterations in nitric oxide synthesis are of pathophysiologic importance in heart failure. Nitric oxide (NO) can exert negative inotropic and cytotoxic effects on cardiomyocytes. A number of studies have shown altered nitric oxide production by the endothelial constitutive isoform of nitric oxide synthase (NOS III), but there is little information on the role of NOS II. Expression of NOS II could lead to excessive production of NO in the myocardium and affect cardiac contractility. METHODS: NOS II mRNA expression in myocardial tissue of 18 patients with idiopathic dilated cardiomyopathy (DCM), 7 patients with ischemic cardiopathy and severe ventricular dysfunction (ISCH), 4 patients with acute myocardial infarction (AMI) and 11 controls. Serum concentration of NO2-/NO3- (NOx) was also measured. RESULTS: NOS II gene expression occurred in all the patients with DCM, in 1 out of the 7 ISCH patients, in 2 out of the 4 patients with AMI and in none of the controls. Moreover, DCM patients showed a significant 6-fold increase in NOx concentration (253+/-47 nm/ml) as compared to controls (40+/-2 nm/ml) P < 0.001, a phenomenon not observed in ISCH patients (56+/-3 nm/ml). CONCLUSIONS: NOS II expression occurs in failing human cardiac myocytes and can play an specific role in the pathogenesis of DCM.

Cardiomyopathy, Dilated↗
PubMed2000

Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure.

AIMS: The aim of the study was to assess the incidence and clinical implications of increased plasma angiotensin II despite chronic ACE inhibitor therapy in patients with heart failure. METHODS AND RESULTS: The studied population consisted of 70 patients (mean age 59+/-9 years). Plasma renin activity and plasma concentration of aldosterone, norepinephrine, atrial natriuretic peptide, angiotensin II, tumour necrosis factor, interleukin-6 and interleukin-1B were assessed at 6 months of ACE inhibitor therapy. Mean left ventricular ejection fraction was 24+/-5% and the end-systolic and end-diastolic diameters were 59+/-9 and 71+/-8 mm, respectively. Despite chronic enalapril or captopril therapy, 35 patients (50%) had increased plasma angiotensin II (median 33 pg. ml(-1), range 17-84), while it was in the normal range in the remaining 35 patients (median 10 pg. ml(-1), range 5-15). Plasma renin activity (P=0.005), interleukin-6 (P=0.004), New York Heart Association functional class III-IV (P=0. 006), furosemide dose (P=0.01), lack of beta-blocker therapy (P=0. 04) and norepinephrine (P=0.04) were univariately associated with increased angiotensin II. Multivariate regression analysis identified the plasma renin activity (0.0004), norepinephrine (0.02) and interleukin-6 (0.03) as independent predictors of plasma angiotensin II. During follow-up (35+/-29 months), nine (12.8%) patients died and 13 had new heart failure episodes. Increased plasma angiotensin II, despite ACE inhibitor therapy, was a significant predictor of death or heart failure according to the Kaplan-Meier survival method by log rank test (P=0.002). CONCLUSION: Fifty per cent of patients with heart failure, ha increased plasma angiotension II despite chronic ACE inhibitor therapy. These patients had higher neurohormonal activation and poor prognosis.

Angiotensin II↗
PubMed2000

Hepatocyte-derived cysteinyl leukotrienes modulate vascular tone in experimental cirrhosis.

BACKGROUND & AIMS: The leukotrienes C(4)/D(4)/E(4) (cysteinyl-LTs) are 5-lipoxygenase (5-LO)-derived eicosanoids with potent vasoconstrictor, proliferative, and profibrogenic properties that may participate in key pathophysiologic events in liver cirrhosis. We examined the cysteinyl-LT biosynthetic pathway in liver tissue and purified liver cells isolated from rats with carbon tetrachloride-induced cirrhosis, and assessed the vasoactive properties of LTD(4) in hepatic stellate cells (HSCs) and anesthetized rats. METHODS & RESULTS: Liver homogenates from cirrhotic rats had increased 5-LO mRNA and cysteinyl-LT content, as determined by Northern blot and enzyme immunoassay, respectively. In isolated rat liver cells, 5-LO mRNA expression was found to be restricted to Kupffer cells. However, among the liver cells (i.e., hepatocytes, Kupffer cells, HSCs, and sinusoidal endothelial cells), hepatocytes exhibited the highest ability to generate cysteinyl-LTs from the unstable intermediate LTA(4). Hepatocytes from cirrhotic rats showed an enhanced baseline generation of cysteinyl-LTs, but their ability to synthesize cysteinyl-LTs from exogenous LTA(4) was found to be similar to that of hepatocytes from normal animals. Both LTD(4) and hepatocyte-conditioned medium increased intracellular Ca(2+) concentration and induced contraction in HSCs, suggesting that hepatocyte-derived cysteinyl-LTs could act in a paracrine fashion on nearby nonparenchymal liver cells. The relevance of these in vitro findings was further established in vivo by the observation that LTD(4) significantly increased portal pressure in anesthetized rats. CONCLUSIONS: These data suggest a role for hepatocyte-derived cysteinyl-LTs in mediating hepatic vascular tone abnormalities in cirrhosis.

Animals↗
PubMed2000

Follicular fluid concentrations of adrenomedullin, vascular endothelial growth factor and nitric oxide in IVF cycles: relationship to ovarian response.

Marked granulosa cell proliferation along with important changes in the vascular bed of the ovary characterize IVF cycles associated with multiple follicular growth and maturation. The present report investigated follicular fluid (FF) and circulating concentrations of adrenomedullin, vascular endothelial growth factor (VEGF) and nitric oxide (NO) in 70 IVF patients (14 of whom became pregnant); these three vasoactive substances may be implicated in extensive ovarian tissue remodelling. Serum and FF concentrations of oestradiol and progesterone were also measured in the 70 IVF cycles studied. Follicular fluid concentrations of VEGF and adrenomedullin but not nitrite/nitrate (the two stable oxidation products of NO metabolism) were significantly higher (P < 0.0001) than the corresponding circulating concentrations. Follicular fluid concentrations of oestradiol and progesterone were not correlated with those of adrenomedullin, VEGF or nitrite/nitrate. No relationship existed between circulating concentrations of adrenomedullin, VEGF or nitrite/nitrate on the day of oocyte aspiration and parameters of ovarian response to gonadotrophin stimulation. In contrast, FF adrenomedullin concentration showed a direct relationship with day 3 FSH serum concentration (r = 0.53, P < 0.01) and the number of ampoules of gonadotrophin administered (r = 0.36, P < 0.005), but an inverse correlation with the total number of oocytes retrieved (r = -0.29, P < 0.01) and the number of mature oocytes (r = -0.25, P < 0. 05). A positive correlation was found for FF VEGF concentration and chronological age (r = 0.29, P < 0.05) and ampoules of gonadotrophins administered (r = 0.30, P < 0.05). There was no relationship between nitrite/nitrate FF concentrations and parameters of ovarian response. Neither serum concentrations nor FF concentrations of adrenomedullin, VEGF or nitrite/nitrate were correlated with IVF outcome. This study suggested for the first time that increased FF concentrations of adrenomedullin can be a marker of decreased ovarian response in IVF. Our results also provide further evidence favouring an association between FF VEGF and patient's age, while on the basis of our findings NO measurements are not a useful marker of ovarian response.

Adrenomedullin↗