Biomedical subjects

A Bertolini

Publications and source records attributed to A Bertolini.

At least 55 records · Page 3Linked to original sources

PubMed1999

l-Sulpiride, at a low, non-neuroleptic dose, prevents conditioned fear stress-induced freezing behavior in rats.

Antidepressant drugs are effective in anxiety states, including panic disorder. Both clinical and animal studies indicate that l-sulpiride, at low, non-neuroleptic doses, has antidepressant activity. The present study examined the effect of an antidepressant dose of l-sulpiride (4 mg/kg per day SC), compared with a well-established antidepressant drug (fluoxetine, 3 mg/kg per day SC), in a rat model of anticipatory anxiety/panic behavior: conditioned fear stress-induced freezing behavior. Long-term (26 days) administration of l-sulpiride almost completely abolished freezing, a similar effect being produced by fluoxetine (freezing duration, in seconds: controls, 148.1 +/- 29.6; l-sulpiride, 27.5 +/- 8.3; fluoxetine, 72.0 +/- 15.2). The same doses of l-sulpiride (4 mg/kg SC) and fluoxetine (3 mg/kg SC) had no effect when administered for shorter periods (1, 5, or 12 days). No effect was produced by the long-term (26 days) administration of a neuroleptic dose of l-sulpiride (20 mg/kg per day SC). These results demonstrate that long-term administration of low, non-neuroleptic doses of l-sulpiride, is highly effective in an animal model of anticipatory anxiety/panic behavior.

Animals↗

PubMed1999

Gamma-hydroxybutyrate increases gastric emptying in rats.

The influence of gamma-hydroxybutyrate (GHB; 10, 50 or 100 mg/kg orally) and of its receptor antagonist, NCS-382 (25, 100 or 200 mg/kg orally, and 100 or 200 mg/kg intraperitoneally), on gastric emptying was studied in rats by measuring the serum level of acetaminophen (20 mg/rat orally, 30 min after GHB or NCS-382) 15, 30, 45 and 60 min after acetaminophen administration, or the amount of acetaminophen still present in the stomach 30 min after its administration. The highest dose of GHB produced a significant increase in 15 and 30 min serum levels of acetaminophen, indicating an acceleration of gastric emptying. A similar result was obtained with the prokinetic drug cisapride, at the oral dose of 2 mg/kg. On the other hand, NCS-382 significantly and dose-dependently reduced the serum levels of acetaminophen at every time of blood sampling, indicating a delay of gastric emptying, an effect confirmed by the amount of acetaminophen still present in the stomach 30 min after administration. Moreover, NCS-382 antagonized the prokinetic effect of GHB. These results may suggest for GHB (and/or possibly for its metabolites) a role in rat stomach motility.

Acetaminophen↗

PubMed1999

Corticotropin-releasing factor (CRF) induced anorexia is not influenced by a melanocortin 4 receptor blockage.

CRF and melanocortin (MSH/ACTH) peptides share a number of central effects including anorexia and grooming. The effects of CRF may be secondary, due to CRF's effects on melanocortin peptide release. We investigated if the newly discovered selective melanocortin 4 receptor antagonist HS014 could influence CRF induced anorexia and grooming. The data show that ICV administration of CRF (3 mg/rat), significantly reduced food intake, feeding time and feeding episodes whereas it increased grooming time and grooming episodes. HS014 (5 mg/rat), that previously has been shown to antagonize the anorectic effect and the excessive grooming induced by alpha-MSH, did however not influence any of the behavioral effects induced by CRF when the peptides were administered together. The data indicate that the anorectic and grooming effects of CRF are independent of pathways involving the MC4 receptors. These data suggest that the anorectic and grooming effect of CRF are not due to a secondary effect caused by increase in release of melanocortins acting on the central MC receptors.

Adrenocorticotropic Hormone↗

PubMed1999

Influence of S-adenosyl-L-methionine on chronic mild stress-induced anhedonia in castrated rats.

1. S-adenosyl-L-methionine (SAMe) is the most important methyl donor in the brain and is essential for polyamine synthesis. Methyl group deficiency in the brain has been implicated in depression; on the other hand, polyamines enhance phosphorylation processes, and phosphorylation of functional proteins in neurons in involved in the therapeutic mechanisms of antidepressants. 2. The effect of SAMe in an animal model of 'depression', the chronic mild stress-induced anhedonia, was studied using long-term castrated male and female Lister hooded rats. 3. Chronic daily exposure to an unpredictable sequence of mild stressors produced, within 3 weeks, a significant reduction of the consumption of a sucrose solution. SAMe (100, 200 or 300 mg kg-1 daily i.m.) while having no influence on sucrose intake in non-stressed animals, dose-dependently reinstated sucrose consumption within the first week of treatment, both in male and in female stressed rats. Imipramine (10 mg kg-1 daily i.p.) produced a similar effect after a 3 week treatment. 4. Similarly, a palatable food reward-induced place preference conditioning was developed in SAMe (200 or 300 mg kg-1 daily i.m.)--and in imipramine (10 mg kg-1 daily i.p.)--treated chronically stressed animals (males and females), whilst it could not be obtained in vehicle-treated rats. 5. Moreover, the same doses of SAMe (but not of imipramine) restored the exploratory activity and curiosity for the environment (rearing), in the open-field test. 6. While imipramine caused a blockade of the growth throughout the treatment, SAMe produced only a transient growth arrest during the first week of treatment. 7. These results show that SAMe reverses an experimental condition of 'depression-like' behaviour in rats, the effect being more rapid and complete than that of imipramine, and without apparent side effects.

Animals↗

PubMed1999

Adrenocorticotropin reverses vascular dysfunction and protects against splanchnic artery occlusion shock.

1. Tumour necrosis factor (TNF-alpha) is involved in the pathogenesis of splanchnic artery occlusion (SAO) shock. On the other hand, inhibition of TNF-alpha is an important component of the mechanism of action of melanocortins in reversing haemorrhagic shock. We therefore investigated the effects of the melanocortin peptide ACTH-(1 - 24) (adrenocorticotropin fragment 1 - 24) on the vascular failure induced by SAO shock. 2. SAO-shocked rats had a decreased survival rate (0% at 4 h of reperfusion, while sham-shocked rats survived for more than 4 h), enhanced serum TNF-alpha concentrations (755+/-81 U ml-1), decreased mean arterial blood pressure, leukopenia, and increased ileal leukocyte accumulation, as revealed by means of myeloperoxidase activity (MPO=9.4+/-1 U g-1 tissue). Moreover, aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE, 1 nM - 10 microM) (Emax and ED50 in shocked rats=7.16 mN mg-1 tissue and 120 nM, respectively; Emax and ED50 in sham-shocked rats=16.31 mN mg-1 tissue and 100 nM, respectively), reduced responsiveness to acetylcholine (ACh, 10 nM-10 microM) (Emax and ED50 in shocked rats=30% relaxation and 520 nM, respectively; Emax and ED50 in sham-shocked rats=82% relaxation and 510 nM, respectively) and increased staining for intercellular adhesion molecule-1 (ICAM-1). 3. ACTH-(1 - 24) [160 microg kg-1 intravenously (i.v.), 5 min after SAO] increased survival rate [SAO+ACTH-(1 - 24)=80% at 4 h of reperfusion], reversed hypotension, reduced serum TNF-alpha (55+/-13 U ml-1), ameliorated leukopenia, reduced ileal MPO (1.2+/-0.2 U g-1 tissue), restored the reactivity to PE, improved the responsiveness to ACh and blunted the enhanced immunostaining for ICAM-1 in the aorta. 4. Adrenalectomy only in part - but not significantly - reduced the ACTH-induced shock reversal, the survival rate of SAO+ACTH-(1 - 24) adrenalectomized rats being 60% at 4 h of reperfusion; and methylprednisolone (80 mg-1 i.v., 5 min after SAO) had a non-significant effect (10% survival) at 4 h of reperfusion. 5. The present data show that melanocortins are effective also in SAO shock, their effect being, at least in part, mediated by reduced production of TNF-alpha. Furthermore, they demonstrate, for the first time, that this inhibition is responsible for the adrenocorticotropin-induced reversal of vascular failure and leukocyte accumulation.

Adrenocorticotropic Hormone↗

PubMed1999

Relationship between dental pain perception and 24 hour ambulatory blood pressure: a study on 181 subjects.

OBJECTIVE: To investigate dental pain perception in a large group of essential hypertensive subjects. METHODS: A total of 130 hypertensive patients together with 51 normotensive subjects were submitted to tooth-electrical stimulation to determine the dental pain threshold (occurrence of pulp sensation) and tolerance (time when the subject asked for the test to be stopped). Blood pressure was measured at rest, before pain perception evaluation, and during a 24 h period by ambulatory monitoring. RESULTS: The normotensive and hypertensive subjects differed with regard to pain threshold (P = 0.002) and tolerance (P = 0.01). Pain perception variables were significantly correlated with both resting blood pressure and 24 h, diurnal and nocturnal arterial pressures, the correlation between pain threshold and 24 h systolic blood pressure being the most significant (r = 0.31, P < 0.0001). By contrast, parameters indicating 24 h blood pressure variability (percentage of nocturnal blood pressure reduction and 24 h blood pressure variation coefficients) were not associated with pain perception. Moreover, among the hypertensives only, a significant relationship was observed between pain sensitivity and both baseline and 24 h pressures. No association was found when pain perception and blood pressure were correlated in the normotensive group. CONCLUSIONS: The correlation between both baseline and 24 h blood pressure and pain perception has been confirmed in a large group study of normotensive and hypertensive subjects. Moreover, even among the hypertensive range of blood pressure, the higher the blood pressure is, the lower the sensitivity to pain is. These findings strengthen the hypothesis of a role of the degree of blood pressure elevation in modulating pain sensitivity.

Adult↗

PubMed1999

Individualized versus standardized analysis of ambulatory blood pressure profile: relationship with left ventricular characteristics.

OBJECTIVE: Objective To determine whether the use of patients' individual awake/asleep patterns instead of fixed day/night intervals would influence the correlations between blood pressure values and left ventricular morpho-functional characteristics. METHODS: We enrolled 167 never-treated hypertensives (clinic blood pressures >160 mmHg systolic or 90 mmHg diastolic, or both): 32 had 24h blood pressures <130/80 mmHg [white-coat hypertensives (WCH)] and 135 had 24h blood pressures >130 mmHg systolic or 80 mmHg diastolic, or both (hypertensives). Each patient underwent left ventricular echocardiographic examination and 24h ambulatory blood pressure monitoring, evaluated twice, using standard day/night intervals (daytime 0700-2200 h, night-time 2200-0700 h) and using the patient's individual awake/asleep pattern (an individualized scheme). RESULTS: Daytime and night-time blood pressures in WCH and daytime and night-time diastolic blood pressures in hypertensives were not affected by choice of using individualized or standard intervals; daytime systolic blood pressure in hypertensives was significantly higher and night-time systolic blood pressure lower with individualized intervals. The non-dippers (nocturnal decrease in blood pressure <10% of daytime blood pressure) were 31 hypertensives and six WCH with standard day/night intervals and 25 hypertensives and four WCH with individualized intervals; nocturnal falls in systolic and diastolic blood pressures were significantly greater with individualized intervals for both groups. Left ventricular hypertrophy was present in 68 hypertensives and seven WCH; left ventricular systolic function was normal in all and left ventricular diastolic function was impaired in 53 hypertensives and seven WCH. Left ventricular characteristics of WCH were not correlated to blood pressure parameters; left ventricular mass index of hypertensives was directly correlated to 24h, daytime and night-time systolic blood pressures, whereas left ventricular diastolic function was inversely correlated to night-time systolic and diastolic blood pressures. The correlations were not affected by choice of using individual awake/asleep patterns. CONCLUSIONS: Timing day and night in an individualized way seems to improve the evaluation of nocturnal fall in blood pressure, but does not improve the ability to predict the left ventricle's involvement with ambulatory blood pressure monitoring.

Adult↗

PubMed1999

Insulin and diastolic dysfunction in lean and obese hypertensives: genetic influence.

We investigated the influence of genetic predisposition to hypertension by studying the relation between insulin sensitivity and left ventricular (LV) mass and function in untreated lean and obese hypertensives. We selected 50 lean hypertensives with normotensive parents (negative family history of hypertension [F-]), 64 lean hypertensives with 1 or both parents hypertensive (positive family history of hypertension [F+]), 40 obese F- hypertensives, and 43 obese F+ hypertensives. The 4 groups were comparable regarding age, gender, 24-hour blood pressure profile, and known duration of hypertension. We measured glucose, insulin, and C-peptide during fasting and during an oral glucose tolerance test; LV morphology and function were assessed by digitized M-mode echocardiography. Glucose (fasting and test) levels were normal in all and similar among the 4 groups. Insulin and C-peptide (fasting and stimulated) levels were higher in obese hypertensives than in lean hypertensives; at similar body mass index, insulin and C-peptide levels were higher in F+ than in F- groups. Compared with lean hypertensives, obese hypertensives had greater LV mass index; LV systolic function was normal in all and similar among the groups. The indices of LV diastolic function were significantly lower in F+ than in F- groups. LV mass index did not correlate with metabolic parameters; the indices of LV diastolic function were inversely correlated with insulin area during test in only the 2 F+ groups. In conclusion, genetic predisposition to hypertension is associated with a reduced insulin sensitivity and affects the response of the myocardium to increased insulin levels, inducing a greater impairment of diastolic function. Insulin sensitivity and genetic predisposition to hypertension seem to have no influence on LV mass.

Adult↗

PubMed1999

Autonomic function and baroreflex sensitivity during a normal ovulatory cycle in humans.

OBJECTIVE AND DESIGN: Possible variations occurring in the autonomic function during a normal ovulatory cycle have been poorly investigated and it is not known whether the baroreflex sensitivity may change according to the different phases of the cycle. The aim of this study was to evaluate heart rate variability (power spectrum analysis), and baroreceptor sensitivity (alpha-low frequency coefficient) in 13 young women with regular menses during the two phases of the cycle (phase I: 5 +/- 1 days and phase II: 23 +/- 3 days from bleeding). RESULTS: The low frequency/high frequency ratio was significantly higher in the second phase of the cycle (phase I: 2.8 +/- 2.6; phase II: 5.6 +/- 5.8, p < 0.05), in the presence of increased low frequency and reduced high frequency expressed in normalized units-nu-(phase I: 59.8 +/- 16.7 nu and 32.6 +/- 15.6 nu for low frequency and high frequency, respectively; phase II: 67.7 +/- 18 nu and 25.7 +/- 17.5 nu for low frequency and high frequency, respectively; p < 0.05). The alpha-low frequency coefficient, index of baroreflex sensitivity, did not statistically differ in the two phases (phase I: 10.6 +/- 4.5 msec/mm Hg; phase II: 8.9 +/- 4.9 msec/mm Hg; ns). CONCLUSIONS: The power spectrum analysis suggests that the autonomic function may be affected by the ovulatory cycle, sympathetic activation being relatively increased in the second phase. On the contrary, the baroreceptor function seems to be scarcely influenced by the two phases of the menstrual cycle.

Adult↗

PubMed1999

Evidence that melanocortin 4 receptor mediates hemorrhagic shock reversal caused by melanocortin peptides.

Melanocortin peptides are known to be extremely potent in causing the sustained reversal of different shock conditions, both in experimental animals and humans; the mechanism of action includes an essential brain loop. Three melanocortin receptor subtypes are expressed in brain tissue: MC(3), MC(4,) and MC(5) receptors. In a volume-controlled model of hemorrhagic shock in anesthetized rats, invariably causing the death of control animals within 30 min after saline injection, the i.v. bolus administration of the adrenocorticotropin fragment 1-24 (agonist at MC(4) and MC(5) receptors) at a dose of 160 microg/kg i.v. (54 nmol/kg) produced an almost complete and sustained restoration of cardiovascular and respiratory functions. An equimolar dose of gamma(1)-melanocyte stimulating hormone (selective agonist at MC(3) receptors) was completely ineffective. The selective antagonist at MC(4) receptors, HS014, although having no influence on cardiovascular and respiratory functions per se, dose-dependently prevented the antishock activity of adrenocorticotropin fragment 1-24, with the effect being complete either at the i.v. dose of 200 microg/kg or at the i.c.v. dose of 5 microg/rat (17-20 microg/kg). We concluded that the effect of melanocortin peptides in hemorrhagic shock is mediated by the MC(4) receptors in the brain.

Animals↗

PubMed1998

Differential influence of a selective melanocortin MC4 receptor antagonist (HS014) on melanocortin-induced behavioral effects in rats.

We injected i.c.v. the natural agonist alpha-MSH (melanocyte-stimulating hormone) and the first selective melanocortin MC4 receptor antagonist HS014 (cyclic [AcCys11, D-Nal14, Cys18, Asp-NH(2)22]-beta-MSH(11-22) in rats and scored a number of behavioral effects which have been related to the melanocortic peptides. The results showed that HS014 (5 microg/rat) completely blocked alpha-MSH (3 and 5 microg/rat)-induced grooming, yawning and stretching. Penile erections induced by alpha-MSH were, however, only partially blocked by HS014. Injections of alpha-MSH decreased food intake in food-deprived rats, whereas HS014 increased food intake. When the peptides were given together, the food intake was similar to that of saline treated controls. Locomotion/exploration and resting were not influenced by either peptide. Our data show that exogenous beta-MSH decreases food intake, and that an endogenous central melanocortinergic inhibitory tone on feeding prevails which can be blocked with HS014, leading to an increase in food intake. Our data also provide evidence that grooming, stretching and yawning in rats may be mediated by the melanocortin MC4 receptor, whereas penile erections might perhaps be mediated by some other melanocortin receptor.

Animals↗

PubMed1998

Complicated pericardial cyst: atypical anatomy and clinical course.

Pericardial cysts are usually detected by chance are are clinically silent in most cases. Nevertheless, symptoms and serious complications may occur. We describe a case of pericardial cyst diagnosed in an 8-year-old boy who was admitted with chest pain. Echocardiography revealed a mild to moderate pericardial effusion and a 7.5 x 5.5 cm intrapericardial echo-free lesion consistent with a pericardial cyst. Surgery was carried out 3 days afterward because of the patient's worsening condition, the progressive increase of pericardial effusion, and the onset of initial signs of cardiac tamponade. The cyst showed a long and easily movable vascular pedicle and inflammatory areas involving the pericardial surface. Like the pericardial effusion, the contents of the mass appeared as serosanguineous fluid on aspiration. Histologic examination confirmed the diagnosis of pericardial cyst and showed findings according to ischemia-related lesions of the cyst. The coexistence of pericardial cyst and cardiac tamponade is very unusual. The atypical anatomy and clinical course suggest a distinct and so far undescribed pathogenetic mechanism for this association: the torsion of a vascular pedicle and the subsequent development of ischemia-related lesions of the cyst.

Cardiac Tamponade↗

PubMed1998

Adrenocorticotropin counteracts the increase in free radical blood levels, detected by electron spin resonance spectrometry, in rats subjected to prolonged asphyxia.

We investigated the influence of the adrenocorticotropic fragment 1-24 [ACTH-(1-24)] on the blood levels of highly-reactive free radicals in a rat model of prolonged asphyxia. Anesthetized animals were endotracheally intubated and mechanically ventilated with room air; after a 10 min stabilization period, the ventilator was turned off to induce asphyxia for 5 min; then, the ventilator was turned back on, and, simultaneously, the rats were intravenously treated with either ACTH-(1-24) (160 microg/kg in a volume of 1 ml/kg) or equivolume saline. Free radicals were detected in arterial blood by electron spin resonance spectrometry using an ex vivo method that avoids injection of the spin-trapping agent employed (alpha-phenyl-N-tert-butylnitrone). Arterial pressure, electrocardiogram (ECG) and electroencephalogram (EEG) were monitored for the 60 min observation period, or until prior death. At the end of the 5 min period of respiratory arrest, blood levels of free radicals were about four times higher than those of the basal, pre-asphyxia condition, arterial pressure had dramatically decreased, ECG showed marked bradycardia and signs of ischemic damage and the EEG had become isoelectric. Treatment with ACTH-(1-24) produced an immediate normalization of the blood levels of free radicals, associated with a restoration of cardiovascular function and full recovery of EEG within 30-45 min; all the saline-treated rats, on the other hand, died within 6.89 +/- 0.96 min. These results provide direct evidence that in a severe condition of prolonged asphyxia there is a rapid and massive production of highly-reactive free radicals and suggest that the resuscitating effect of adrenocorticotropin fragments in severe hypoxic conditions may be largely due to the inhibition of free radical overproduction during tissue reoxygenation.

Adrenocorticotropic Hormone↗

PubMed1998

Diabetic rats are unresponsive to the penile erection-inducing effect of intracerebroventriculary injected adrenocorticotropin.

The penile erection-inducing effect of intracerebroventricularly (i.c.v.) injected adrenocorticotropin-(1-24) [ACTH-(1-24)] (4 or 10 microg/animal) was almost completely absent in diabetic rats, either 8 days or 2 months after streptozotocin administration. The other behavioral symptoms (stretching, yawning, excessive grooming) were unevenly affected: stretching was significantly reduced either in early or in long-standing diabetes; yawning was practically absent in early diabetes and significantly reduced at the highest dose of ACTH-(1-24) in long-standing diabetes; grooming was reduced only at the highest dose of ACTH-(1-24), both in early and in long-standing diabetes. The fact that ACTH-induced penile erections (a centrally mediated effect) are practically absent even a few days after streptozotocin injection suggests that diabetes mellitus-induced penile dysfunction occurs, at least in part, through central mechanisms, and is not solely the consequence of peripheral nerve and vascular lesions.

Animals↗

PubMed1998

Tumour necrosis factor-alpha as a target of melanocortins in haemorrhagic shock, in the anaesthetized rat.

The cytokine tumour necrosis factor-alpha (TNF-alpha) is involved (mostly through the activation of inducible nitric oxide synthase) in the pathogenesis of circulatory shock. On the other hand, melanocortin peptides are potent and effective in reversing haemorrhagic shock, both in animals (rat, dog) and in humans. This prompted us to study the influence of the melanocortin peptide ACTH-(1-24) on the blood levels of TNF-alpha in haemorrhage-shocked rats and on the in vitro production of TNF-alpha by lipopolysaccharide (LPS)-activated macrophages. Plasma levels of TNF-alpha were undetectable before starting bleeding and greatly increased 20 min after bleeding termination in saline-treated rats. In rats treated with ACTH-(1-24) the almost complete restoration of cardiovascular function was associated with markedly reduced levels of TNF-alpha 20 min after bleeding termination. On the other hand, ACTH-(1-24) did not influence TNF-alpha plasma levels in sham-operated, unbled rats. In vitro, ACTH-(1-24) (25-100 nM) dose-dependently reduced the LPS-stimulated production of TNF-alpha by peritoneal macrophages harvested from untreated, unbled rats. These results indicate that inhibition of TNF-alpha overproduction may be an important component of the mechanism of action of melanocortins in reversing haemorrhagic shock.

Anesthesia↗

PubMed1998

Reactivity of blood pressure to mental arithmetic stress test, stress-test recovery time, and ambulatory blood pressure in hypertensive and normotensive subjects.

BACKGROUND: Laboratory mental stress testing and 24 h ambulatory blood pressure monitoring may analyse reactivity of blood pressure during provoked stress and stressful situations in daily-life, respectively. OBJECTIVE: To evaluate whether the responses to a mental stress test and during the stress-test recovery time were associated with ambulatory blood pressure parameters. METHODS: Fifty-two untreated male subjects (22 normotensives and 30 hypertensives) were subjected both to mental arithmetic stress testing and ambulatory blood pressure monitoring. RESULTS: We found a positive correlation between baseline and peak-test blood pressures during the stress test and 24 h blood pressures. Maximal values of systolic and diastolic blood pressures measured during the 24 h were also correlated to the maximal systolic and diastolic blood pressures reached during the stress test ( P < 0.001). We observed no relationship between reactivity during the stress test and 24 h parameters. On the contrary, changes in diastolic blood pressure during the time of recovery from the stress test (expressed as percentage-change scores) were correlated to the 24 h diastolic blood pressure parameters, the diastolic load being the most closely associated variable. CONCLUSION: The absence of relationships between variations in blood pressure during the provoked stress and ambulatory monitoring parameters indicates that reactivity of blood pressure to an acute stress does not predict the 24 h profile. However, the correlation between the maximal blood pressure measured by ambulatory monitoring and that observed during stress testing indicates that the maximal 24 h values may show the extreme blood pressure response (like the one provoked acutely by a laboratory stress test) of an individual subject. The correlation between the percentage-change score during the recovery time of diastolic blood pressure and the 24 h diastolic load could account forr a lower than normal capacity for recovery of subjects with persistently high blood pressures.

Journal Article↗

PubMed1997

Adrenocorticotropin normalizes the blood levels of nitric oxide in hemorrhage-shocked rats.

Anesthetized rats were subjected to volume-controlled hemorrhagic shock by stepwise bleeding. Besides cardiovascular and respiratory functions, nitric oxide (NO)-hemoglobin formation in arterial blood was directly evaluated by means of electron spin resonance spectroscopy. During hemorrhagic shock there was a massive increase in NO-hemoglobin, associated with a fall in mean arterial pressure, pulse pressure, respiratory rate and heart rate, and there was a further increase in NO-hemoglobin 15 min after intravenous (i.v.) treatment with saline. All rats died within 30 min. The reversal of the shock condition induced by the i.v. injection of the adrenocorticotropin (ACTH) fragment 1-24 (160 microg/kg, 5 min after bleeding termination) was associated with a prompt disappearance of NO-hemoglobin. Also S-methylisothiourea (3 mg/kg i.v.), a selective inhibitor of inducible NO synthase, provoked a disappearance of NO-hemoglobin and reversal of the shock condition. The present results provide a direct demonstration that volume-controlled hemorrhagic shock is associated with highly increased blood levels of NO, as indicated by increased NO-hemoglobin, and indicate that ACTH-induced reversal of the shock condition is associated with the normalization of NO blood levels, and a parallel improvement of cardiovascular and respiratory functions. This occurs probably through the inhibition of inducible NO synthase, as suggested by the fact that S-methylisothiourea, a selective inhibitor of this NO synthase isoform, produced the same results.

Adrenocorticotropic Hormone↗

PubMed1997

Sexual impotence is associated with a reduced production of oxytocin and with an increased production of opioid peptides in the paraventricular nucleus of male rats.

Oxytocin plays a physiological stimulatory role on sexual behavior. Conversely, opioid neuropeptides play a physiological inhibitory role. Here we show that in sexually impotent rats there is a reduced expression of oxytocin mRNA and an increased expression of proenkephalin and pro-dynorphin mRNA in the paraventricular nucleus of hypothalamus (PVN), a brain structure of key importance for sexual behavior. These data suggest that an imbalance in the production of oxytocin and of opioid peptides in the PVN, with prevalence of opioid peptides, may underlie a condition of sexual impotence.

Animals↗