Evelin Capellari Cárnio

Simvastatin decreases nitric oxide overproduction and reverts the impaired vascular responsiveness induced by endotoxic shock in rats.

Lipopolysaccharides (LPS) can be used to induce experimental endotoxic shock, which is characterized by a significant decrease in mean arterial pressure (MAP) and a decreased vasoconstrictor response that have been attributed to excessive nitric oxide production. Inhibitors of 3-hydroxi-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), in addition to lowering serum cholesterol levels, exert many pleiotropic effects, including anti-inflammatory action. In the present study, we investigated the effect of simvastatin, an HMG-CoA reductase inhibitor, on the production of nitric oxide and the cardiovascular response to LPS. Male Wistar rats were pretreated with different doses of simvastatin (10, 20, 40, and 80 mg/kg, i.p.) or saline 20 min before i.v. injection of LPS (1.5 mg/kg) or saline (control). MAP was continuously recorded and nitrate plasma concentration was determined during the 6-h experimental session at 1-h intervals. The pressor response to phenylephrine (1 &mgr;g/kg) was evaluated before and 6 h after LPS administration. In the LPS-treated group, there was a time-dependent increase in nitrate plasma concentration (P < 0.001), and this response was decreased in simvastatin pretreated rats (P < 0.001). We also observed that LPS decreased the pressor response to phenylephrine (P < 0.001), an effect that was reverted by simvastatin pretreatment (P < 0.05). However, simvastatin did not modify the decrease of MAP induced by LPS. We concluded that simvastatin decreases nitrate plasma concentration in response to LPS and recovers vascular responsiveness during an experimental endotoxic shock. These data suggest the potential use of HMG-CoA reductase inhibitors as a coadjuvant in the treatment of septic shock.

Inducible nitric oxide synthase pathway in the central nervous system and vasopressin release during experimental septic shock.

BackgroundSeptic shock is characterized by arteriolar vasodilation and hypotension. We have tested the hypothesis that nitric oxide arising from inducible nitric oxide synthase in the central nervous system is responsible for the deficiency in vasopressin release and consequent hypotension during experimental septic shock. Methods and ResultsSeptic shock was induced in male Wistar rats by intravenous injection of 1.5 mg/kg lipopolysaccharide. After lipopolysaccharide administration, we found a significant decrease in mean arterial pressure with a concomitant increase in heart rate, a significant decrease in diuresis, and a transitory decrease in body temperature. An increase in plasma vasopressin concentrations occurred in these animals and was present for 2 hrs after lipopolysaccharide administration, returning close to basal concentrations thereafter and remaining unchanged for the next 24 hrs. When lipopolysaccharide was combined with central administration of aminoguanidine, an inducible nitric oxide synthase inhibitor, we observed a sustained increase in plasma vasopressin concentration and in the maintenance of blood pressure at 4 and 6 hrs after lipopolysaccharide treatment compared with rats treated with lipopolysaccharide alone. ConclusionThese data indicate that central nitric oxide arising from the inducible nitric oxide synthase pathway plays an important inhibitory role in vasopressin release during experimental septic shock and may be responsible for the hypotension occurring in this vasodilatory shock.

Assessment of the techniques of blood pressure measurement by health professionals

OBJECTIVE To assess blood pressure measurement by health professionals of a public hospital in S o Paulo State. METHODS Semi-structured interviews and direct observation were performed with a verification list according to the criteria reported by Perloff et al. One hundred and five health professionals took part in the study. After measuring blood pressure, the level of concordance between the way the procedure was performed and the recommended one was assessed. RESULTS Nurses and nurses aides abided by 40% of the recommended procedures for adequate blood pressure measurement. The other categories of health professionals (nursing and medicine teachers, physicians, residents, and nursing students) abided by approximately 70%. CONCLUSION Permanent educational activities aiming at standardizing blood pressure measurement should be implemented among the different categories of health professionals.

Role of nitric oxide in systemic vasopressin-induced hypothermia

It has been reported that arginine vasopressin (AVP) plays a thermoregulatory action, but very little is known about the mechanisms involved. In the present study, we tested the hypothesis that nitric oxide (NO) plays a role in systemic AVP-induced hypothermia. Rectal temperature was measured before and after AVP, AVP blocker, or N G-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) injection. Control animals received saline injections of the same volume. The basal body temperature (Tb) measured in control animals was 36.53 ± 0.08°C. We observed a significant ( P < 0.05) reduction in Tb to 35.44 ± 0.19°C after intravenous injection of AVP (2 μg/kg) and to 35.74 ± 0.10°C after intravenous injection ofl-NAME (30 mg/kg). The systemic injection of the AVP blocker [β-mercapto-β,β-cyclopentamethylenepropionyl1, O-Et-Tyr2,Val4,Arg8]vasopressin (10 μg/kg) caused a significant increase in Tb to 37.33 ± 0.23°C, indicating that AVP plays a tonic role by reducing Tb. When the treatments with AVP and l-NAME were combined, systemically injected l-NAME blunted AVP-induced hypothermia. To assess the role of central thermoregulatory mechanisms, a smaller dose ofl-NAME (1 mg/kg) was injected into the third cerebral ventricle. Intracerebroventricular injection ofl-NAME caused an increase in Tb, but when intracerebroventricular l-NAME was combined with systemic AVP injection (2 μg/kg), no change in Tb was observed. The data indicate that central NO plays a major role mediating systemic AVP-induced hypothermia.It has been reported that arginine vasopressin (AVP) plays a thermoregulatory action, but very little is known about the mechanisms involved. In the present study, we tested the hypothesis that nitric oxide (NO) plays a role in systemic AVP-induced hypothermia. Rectal temperature was measured before and after AVP, AVP blocker, or NG-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor) injection. Control animals received saline injections of the same volume. The basal body temperature (Tb) measured in control animals was 36.53 +/- 0.08 degreesC. We observed a significant (P < 0.05) reduction in Tb to 35.44 +/- 0.19 degreesC after intravenous injection of AVP (2 micrograms/kg) and to 35.74 +/- 0. 10 degreesC after intravenous injection of L-NAME (30 mg/kg). The systemic injection of the AVP blocker [beta-mercapto-beta, beta-cyclopentamethylenepropionyl1,O-Et-Tyr2,Val4,Arg8]vasopressin (10 micrograms/kg) caused a significant increase in Tb to 37.33 +/- 0.23 degreesC, indicating that AVP plays a tonic role by reducing Tb. When the treatments with AVP and L-NAME were combined, systemically injected L-NAME blunted AVP-induced hypothermia. To assess the role of central thermoregulatory mechanisms, a smaller dose of L-NAME (1 mg/kg) was injected into the third cerebral ventricle. Intracerebroventricular injection of L-NAME caused an increase in Tb, but when intracerebroventricular L-NAME was combined with systemic AVP injection (2 micrograms/kg), no change in Tb was observed. The data indicate that central NO plays a major role mediating systemic AVP-induced hypothermia.

A farmacoterapia no idoso: revisão sobre a abordagem multiprofissional no controle da hipertensão arterial sistêmica

The greater prevalence of chronic diseases like systemic arterial hypertension among elderly people results in an increase of drugs use. Therefore, the incidence of a lot of drug-related problems (DRP) rises, and this leads to many health problems in the population. Based on literature, authors emphasize the multidisciplinary team approach (physicians, nurses and pharmacists) to activities directly related with pharmacotherapy for hypertension, granting elderly persons a better comprehension about taking care of their own health, to reduce DRP and achieve satisfactory adherence.La mayor prevalencia de las enfermedades cronicas entre los ancianos, tales como la hipertension arterial sistemica, implica el crecimiento del consumo de medicamentos. En consecuencia, aumenta la incidencia de problemas relacionados a los medicamentos (PRM), dejando a esta poblacion vulnerable a varios problemas de salud. Basados en la literatura, destacamos la actuacion multiprofesional (medico, enfermero y farmaceutico) en las actividades ligadas directamente a la farmacoterapia de la hipertension arterial sistemica, para proporcionar a los ancianos una mayor comprension de los cuidados con su salud, reducir los PRM y alcanzar la adhesion satisfactoria

Evidence for thermoregulation by dopamine D1 and D2 receptors in the anteroventral preoptic region during normoxia and hypoxia

Hypoxia causes a regulated decrease in body temperature (Tb), a response that has been called anapyrexia. Stimulation of dopamine receptors in the central nervous system (CNS) reduces Tb in rats, and dopamine D1 and D2 receptors seem to be involved in this response. Thus, we predicted that injection of SCH 23390 and haloperidol, D1 and partly D2 receptor antagonists, respectively, into the anteroventral preoptic region (AVPO, the thermointegrative region of the CNS) would lessen the hypoxia-induced anapyrexia. We measured Tb of conscious Wistar rats before and after injection of SCH 23390 (50 and 100 ng/100 nl) or haloperidol (50 e 500 ng/100 nl) or their respective vehicles (saline and DMSO 5%) into the AVPO followed by 30 min of hypoxia (7% O2). Vehicles and the lower doses of SCH 23390 and haloperidol had no effect on Tb during normoxia or hypoxia. The higher doses of SCH 23390 and haloperidol attenuated (P<0.05) the drop in Tb elicited by hypoxia. However, this higher haloperidol dose also increased Tb during normoxia. The present data is consistent with the notion that dopamine is an important thermoregulatory neurotransmitter in a way that D2 receptors are mainly involved with maintenance of Tb in euthermia, while D1 receptors are activated to induce hypoxic anapyrexia in the AVPO.

Participation of iNOS-derived NO in hypothalamic activation and vasopressin release during polymicrobial sepsis

Clinical and experimental studies with LPS injection have shown an increase in vasopressin (AVP) secretion in the early phase of severe sepsis, which is subsequently reduced despite persistent hypotension. The aim of this study was to evaluate the role of inducible nitric oxide synthase (iNOS)-derived NO in hypothalamic activation and in AVP release during severe sepsis induced by cecal ligation and puncture (CLP). Male Wistar rats received i.p. injections of aminoguanidine, an iNOS inhibitor, or saline 30 min before CLP or sham surgeries (controls). CLP led to increased plasma nitrate levels, protein leakage and hypotension and caused mortality of 80% by 24 h. Expression of c-fos in paraventricular (PVN), supraoptic (SON) and organum vasculosum of lamina terminalis (OVLT) nuclei, as well as plasma AVP concentration were increased at 6 h but reduced to basal levels 24 h after CLP. Aminoguanidine pre-treatment prevented the increase in plasma nitrate levels and hypotension in the first 6 h. It also reduced AVP secretion and hypothalamic c-fos expression. After 24 h, the pre-treatment reduced plasma nitrate levels, protein leakage and caused a partial recovery of c-fos expression in SON and OVLT but did not affect AVP release. Furthermore, mortality was reduced to 43%. We conclude that during the early phase of severe sepsis hypotension caused by the iNOS-derived NO is partially responsible for the hypothalamic activation and AVP release. In the late phase, however, the iNOS-derived NO prevents brain activation blunting AVP secretion contributing to hypotension, irreversible shock and animal death.

Nitrergic modulation of vasopressin, oxytocin and atrial natriuretic peptide secretion in response to sodium intake and hypertonic blood volume expansion

The central nervous system plays an important role in the control of renal sodium excretion. We present here a brief review of physiologic regulation of hydromineral balance and discuss recent results from our laboratory that focus on the participation of nitrergic, vasopressinergic, and oxytocinergic systems in the regulation of water and sodium excretion under different salt intake and hypertonic blood volume expansion (BVE) conditions. High sodium intake induced a significant increase in nitric oxide synthase (NOS) activity in the medial basal hypothalamus and neural lobe, while a low sodium diet decreased NOS activity in the neural lobe, suggesting that central NOS is involved in the control of sodium balance. An increase in plasma concentrations in vasopressin (AVP), oxytocin (OT), atrial natriuretic peptide (ANP), and nitrate after hypertonic BVE was also demonstrated. The central inhibition of NOS by L-NAME caused a decrease in plasma AVP and no change in plasma OT or ANP levels after BVE. These data indicate that the increase in AVP release after hypertonic BVE depends on nitric oxide production. In contrast, the pattern of OT secretion was similar to that of ANP secretion, supporting the view that OT is a neuromodulator of ANP secretion during hypertonic BVE. Thus, neurohypophyseal hormones and ANP are secreted under hypertonic BVE in order to correct the changes induced in blood volume and osmolality, and the secretion of AVP in this particular situation depends on NOS activity.

Tolerance to lipopolysaccharide is related to the nitric oxide pathway

Repeated administration of lipopolysaccharide (LPS) induces a refractory state to its usual pyrogenic effects which is called endotoxin tolerance. We tested the hypothesis that nitric oxide (NO) participates in the endotoxin tolerance. Single injection of LPS resulted in an elevation in body temperature (Tb), whereas a significant reduction of the thermoregulatory response to LPS was observed to repeated administration of LPS (administered at 48 h intervals). Intracerebroventricular (i.c.v.) injection of L-NAME (a non-selective NO inhibitor of nitric oxide synthesis) markedly enhanced the febrile response to LPS in tolerant rats. The data suggest that NO pathway in the central nervous system plays a role in endotoxin tolerance.

Respiratory and body temperature modulation by adenosine A1 receptors in the anteroventral preoptic region during normoxia and hypoxia

The present study was undertaken to investigate adenosine as a simultaneous mediator of hypoxia-induced hyperventilation and regulated hypothermia in the anteroventral preoptic region (AVPO), the thermointegrative region of the central nervous system (CNS). Accordingly, we predicted that injection of aminophylline and DPCPX, non-selective and A(1) receptor antagonists, respectively, into the AVPO would exacerbate the ventilatory response and lessen the drop in body temperature (T(b)) caused by hypoxia. We measured ventilation (V ) and T(b) of conscious Wistar rats before and after AVPO injection of aminophylline (1 and 10 microg/100 nL) or DPCPX (17.5 and 175 ng/100 nL), or their respective vehicles, followed by 30 min of hypoxia (7% O(2)). Vehicles and the lower doses of both antagonists had no effect on V and T(b) during normoxia or hypoxia. The higher doses of aminophylline and DPCPX increased (P<0.05) the hypoxia-induced hyperventilation, whereas the drop in T(b) elicited by hypoxia was attenuated (P<00.05) by DPCPX only. This higher DPCPX dose also increased T(b) during normoxia. The present data is consistent with the notion that adenosine plays an inhibitory role in respiratory and metabolic regulation, in a way that A(1) receptors stimulation in the AVPO inhibits ventilatory drive during hypoxia and tonically modulates basal T(b).