Cardiovascular function alterations induced by acute paradoxical sleep deprivation in rats.

Sleep loss has been implicated in triggering the hypertension. The goal of the present study was investigated the possible mechanisms underlying cardiovascular alterations after acute paradoxical sleep deprivation (PSD). Male Wistar rats were assigned in two experimental groups: (1) control and (2) PSD for 24 h using the modified single platform method. Paradoxical sleep deprived rats exhibited higher blood pressure, heart rate (HR) and impaired baroreceptor sensitivity. After pharmacological autonomic double blockade (propranolol and methylatropine administration), intrinsic heart rate was decreased after PSD. The PSD rats showed a reduction in the vagal tone without affecting sympathetic tone. Isoproterenol administration (0.001, 0.01 and 1 µg/kg) induced an increase in ΔHR responses in PSD group. Electrocardiographic analysis in response to ß-adrenergic stimulation indicated that PSD contributed to ventricular cardiac arrhythmias. Our findings suggest that acute paradoxical sleep loss induce cardiovascular alterations, autonomic imbalance accompanied by impaired baroreflex sensitivity and increased arrhythmia susceptibility.

Spontaneous subarachnoid haemorrhage from rupture of an anterior communicating artery aneurysm in a patient with pituitary macroadenoma.

The presence of a cerebral aneurysm in patients with pituitary adenoma is a rare event. Diagnostic suspicion may stem from magnetic resonance imaging, which should lead to complementary investigation. As for treatment, even in conditions in which there has been no previous bleeding, the simultaneous approach should be considered, prioritising the aneurysm most of the time. The present report describes the case of a patient with a history of pituitary macroadenoma, who had undergone a partial transsphenoidal resection ten years earlier. Admission to our service occurred after a sudden headache followed by mental confusion. A cranial computed tomography showed subarachnoid haemorrhage and expansive suprasellar lesion. Cerebral angiography showed a saccular aneurysm of the anterior communicating complex. The patient underwent a surgical procedure for microsurgical clipping of the aneurysm and partial resection of the pituitary tumour. We have also included a brief review of the literature on this subject.

Patterns of renal and splanchnic sympathetic vasomotor activity in an animal model of survival to experimental sepsis.

Sepsis causes long-term disability, such as immune dysfunction, neuropsychological disorders, persistent inflammation, catabolism, and immunosuppression, leading to a high risk of death in survivors, although the contributing factors of mortality are unknown. The purpose of this experimental study in rats was to examine renal (rSNA) and splanchnic (sSNA) sympathetic nerve activity, as well as baroreflex sensitivity, in acute and chronic post-sepsis periods. The rats were divided into two groups: control group with naïve Wistar rats and sepsis group with 2-mL intravenous inoculation of Escherichia coli at 108 CFU/mL. Basal mean arterial pressure, heart rate, rSNA, sSNA, and baroreflex sensitivity were evaluated in all groups at the acute (6 h) and chronic periods (1 and 3 months). Basal rSNA and sSNA were significantly reduced in the surviving rats, as was their baroreflex sensitivity, for both pressor and hypotensive responses, and this effect lasted for up to 3 months. A single episode of sepsis in rats was enough to induce long-term alterations in renal and splanchnic sympathetic vasomotor nerve activity, representing a possible systemic event that needs to be elucidated. These findings showed that post-sepsis impairment of sympathetic vasomotor response may be one of the critical components in the inability of sepsis survivors to respond effectively to new etiological illness factors, thereby increasing their risk of post-sepsis morbidity.

Differential effects of estrogen receptors in the rostral ventrolateral medulla in Goldblatt hypertension.

Previous studies have shown that 17ß-estradiol plays a cardioprotective role in the central nervous system (CNS) of male rats. The aim of the present study was to determine the influence of 17ß-estradiol on sympathetic vasomotor activity and blood pressure in a renovascular hypertensive Goldblatt two-kidney one-clip (2K-1C) male rat model. We also determined the influence of angiotensin II AT1 receptor on the expression of estrogen receptors (ERα, ERß, and G protein-coupled ER (GPER)) in the rostral ventrolateral medulla (RVLM) of Goldblatt rats. Experiments were performed in Goldblatt and age-matched control rats six weeks after clipping of renal artery to induce hypertension. Microinjection of 17ß-estradiol into the RVLM led to a greater reduction in mean arterial pressure and renal sympathetic nerve activity in controls than in 2K-1C rats. Microinjection of the GPER agonist G-1 into the RVLM led to a significantly greater increase in mean arterial pressure and renal sympathetic nerve activity in 2K-1C rats. Expression levels of estrogen receptors GPER and ERα, but not ERß, were significantly higher in the RVLM of 2K-1C rats than in that of the control rats. Chronic treatment with losartan significantly reduced the expression levels of estrogen receptors in the RVLM of 2K-1C rats. Taken altogether, the data suggest that the imbalance of actions between ERα and GPER, particularly with the predominance of GPER in the RVLM, contributes to sympathetic overactivation in male rats with Goldblatt hypertension. AT1-Angiotensin II receptor in the RVLM upregulated estrogen receptor expression in male Goldblatt rats.

Use of a levonorgestrel 52-mg intrauterine system in the control of abnormal uterine bleeding in women with inherited bleeding disorders.

OBJECTIVE: To evaluate the efficacy of a levonorgestrel 52-mg intrauterine system (LNG 52-mg IUS) in controlling abnormal uterine bleeding and improving quality of life in women with inherited bleeding disorders. STUDY DESIGN: We assessed 20 participants laboratory diagnosed with inherited bleeding disorders, who presented with abnormal uterine bleeding and were registered in a Central Blood Center. The primary outcomes were menstrual bleeding volume and quality of life before and after LNG 52-mg IUS placement. We used the Pictorial Blood Loss Assessment Chart (PBAC) score for measuring menstrual bleeding and the Short Form-36 Health Survey to assess quality of life before and after LNG 52-mg IUS placement. We also conducted blood tests to evaluate the hematimetric level. Follow-up visits were conducted at 1, 3, 6, and 12 months after LNG 52-mg IUS placement. Statistical analyses were performed using the Friedman non-parametric test. RESULTS: The use of LNG 52-mg IUS reduced uterine bleeding in women with inherited bleeding disorders. The median PBAC score was higher before LNG 52-mg IUS placement than at 3, 6, and 12 months after placement (p < 0.001). The amenorrhea rate was 70% after 12 months. There was an improvement in all eight parameters of quality of life (p < 0.001). The mean hemoglobin, ferritin, and serum iron levels were also higher at 12 months than before LNG 52-mg IUS placement. CONCLUSION: LNG 52-mg IUS placement can effectively control abnormal uterine bleeding in women with inherited bleeding disorders and consequently improve their quality of life. IMPLICATIONS: The results from our study suggest that women with inherited bleeding disorders who present with heavy menstrual bleeding can benefit from the use of a levonorgestrel-releasing intrauterine system similar to women without bleeding disorders.

Chronic renal failure induces genetic instability in multiple organs of Wistar rats.

BACKGROUND: Taking into consideration the strong evidence for a relationship between DNA damage and carcinogenesis, the aim of this study was to investigate whether blood, liver, heart, kidney and brain are particularly sensitive organs for DNA damaging during chronic renal disease by the single-cell gel (comet) assay to predict genetic instability induced by this pathological condition. METHODS: A total of 18 male Wistar rats were divided into two groups: negative control (n = 8) and experimental (n = 10), in which was submitted to the 5/6 renal mass ablation by ligation of two or three branches of the left renal artery and total right nephrectomy during 8 weeks. RESULTS: The results showed that chronic renal disease was able to induce genetic damage in blood, heart, liver and kidney cells as depicted by the mean tail moment. No genetic damage was induced in brain cells, i.e. no significant statistically differences (P > 0.05) were noticed when compared to negative control. CONCLUSION: In conclusion, our results suggest that chronic renal failure could contribute to the damage of DNA at all organs evaluated, except to the brain cells. As DNA damage is an important step in events leading to carcinogenesis, this study represents a relevant contribution to the correct evaluation of the potential health risks associated with kidney disease.

Distinct effects of acute and chronic sleep loss on DNA damage in rats.

The aim of this investigation was to evaluate genetic damage induced in male rats by experimental sleep loss for short-term (24 and 96 h) and long-term (21 days) intervals, as well as their respective recovery periods in peripheral blood, brain, liver and heart tissue by the single cell gel (comet) assay. Rats were paradoxically deprived of sleep (PSD) by the platform technique for 24 or 96 h, or chronically sleep-restricted (SR) for 21 days. We also sought to verify the time course of their recovery after 24 h of rebound sleep. The results showed DNA damage in blood cells of rats submitted to PSD for 96 h. Brain tissue showed extensive genotoxic damage in PSD rats (both 24 and 96 h), though the effect was more pronounced in the 96 h group. Rats allowed to recover from the PSD-96 h and SR-21 days treatments showed DNA damage as compared to negative controls. Liver and heart did not display any genotoxicity activity. Corticosterone concentrations were increased after PSD (24 and 96 h) relative to control rats, whereas these levels were unaffected in the SR group. Collectively, these findings reveal that sleep loss was able to induce genetic damage in blood and brain cells, especially following acute exposure. Since DNA damage is an important step in events leading to genomic instability, this study represents a relevant contribution to the understanding of the potential health risks associated with sleep deprivation.

Differential sympathetic and angiotensinergic responses in rats submitted to low- or high-salt diet.

The present study was designed to evaluate, in Wistar rats, the effect of high- or low-salt diet on the hemodynamic parameters and on the renal and lumbar sympathetic nerve activity. The renal gene expression of the renin angiotensin system components was also evaluated, aiming to find some correlation between salt intake, sodium homeostasis and blood pressure increase. Male Wistar rats received low (0.06% Na, TD 92141-Harlan Teklad), a normal (0.5% Na, TD 92140), or a high-salt diet (3.12% Na, TD 92142) from weaning to adulthood. Hemodynamic parameters such as cardiac output and total peripheral resistance, and the renal and lumbar sympathetic nerve activity were determined (n=45). Plasma renin activity, plasma and renal content of angiotensin (ANG) I and II, and the renal mRNA expression of angiotensinogen, renin, AT1 and AT2 receptors were also measured (n=24). Compared to normal- and low-salt diet-, high-salt-treated rats were hypertensive and developed an increase (P<0.05) in total peripheral resistance and lumbar sympathetic nerve activity. A decrease in renal renin and angiotensinogen-mRNAs and in plasma ANG II and plasma renin activity was also found in salt overloaded animals. The renal sympathetic nerve activity was higher (P<0.05) in low- compared to high-salt-treated rats, and was associated with an increase (P<0.05) in renal ANG I and II and with a decrease (P<0.05) in AT2 renal mRNA. Plasma ANG I and II and plasma renin activity were higher in low- than in normal-salt rats. Our results show that increased blood pressure is associated with increases in lumbar sympathetic nerve activity and total peripheral resistance in high-salt-treated rats. However, in low-salt-treated rats an increase in the renal sympathetic nerve was correlated with an increase in the renal content of ANG I and II and with a decrease in AT2 renal mRNA. These changes are probably in favor of the antinatriuretic response and the sodium homeostasis in the low-salt group.

Sympathetic activation in rats with L-NAME-induced hypertension.

We evaluated the hemodynamic pattern and the contribution of the sympathetic nervous system in conscious and anesthetized (1.4 g/kg urethane, iv) Wistar rats with L-NAME-induced hypertension (20 mg/kg daily). The basal hemodynamic profile was similar for hypertensive animals, conscious (N = 12) or anesthetized (N = 12) treated with L-NAME for 2 or 7 days: increase of total peripheral resistance associated with a decrease of cardiac output (CO) compared to normotensive animals, conscious (N = 14) or anesthetized (N = 14). Sympathetic blockade with hexamethonium essentially caused a decrease in total peripheral resistance in hypertensive animals (conscious, 2 days: from (means +/- SEM) 2.47 +/- 0.08 to 2.14 +/- 0.07; conscious, 7 days: from 2.85 +/- 0.13 to 2.07 +/- 0.33; anesthetized, 2 days: from 3.00 +/- 0.09 to 1.83 +/- 0.25 and anesthetized, 7 days: from 3.56 +/- 0.11 to 1.53 +/- 0.10 mmHg mL-1 min-1) with no change in CO in either group. However, in the normotensive group a fall in CO (conscious: from 125 +/- 4.5 to 96 +/- 4; anesthetized: from 118 +/- 1.5 to 104 +/- 5.5 mL/min) was observed. The responses after hexamethonium were more prominent in the hypertensive anesthetized group. However, no difference was observed between conscious and anesthetized normotensive rats in response to sympathetic blockade. The present study shows that the vasoconstriction in response to L-NAME was mediated by the sympathetic drive. The sympathetic tone plays an important role in the initiation and maintenance of hypertension.

Patterns of renal and splanchnic sympathetic vasomotor activity in an animal model of survival to experimental sepsis

Sepsis causes long-term disability, such as immune dysfunction, neuropsychological disorders, persistent inflammation, catabolism, and immunosuppression, leading to a high risk of death in survivors, although the contributing factors of mortality are unknown. The purpose of this experimental study in rats was to examine renal (rSNA) and splanchnic (sSNA) sympathetic nerve activity, as well as baroreflex sensitivity, in acute and chronic post-sepsis periods. The rats were divided into two groups: control group with naïve Wistar rats and sepsis group with 2-mL intravenous inoculation of Escherichia coli at 108 CFU/mL. Basal mean arterial pressure, heart rate, rSNA, sSNA, and baroreflex sensitivity were evaluated in all groups at the acute (6 h) and chronic periods (1 and 3 months). Basal rSNA and sSNA were significantly reduced in the surviving rats, as was their baroreflex sensitivity, for both pressor and hypotensive responses, and this effect lasted for up to 3 months. A single episode of sepsis in rats was enough to induce long-term alterations in renal and splanchnic sympathetic vasomotor nerve activity, representing a possible systemic event that needs to be elucidated. These findings showed that post-sepsis impairment of sympathetic vasomotor response may be one of the critical components in the inability of sepsis survivors to respond effectively to new etiological illness factors, thereby increasing their risk of post-sepsis morbidity.

Role of the rostral ventrolateral medulla in maintenance of blood pressure in rats with Goldblatt hypertension.

The aim of the present study was to examine the participation of the rostral ventrolateral medulla (RVLM) in the maintenance of hypertension in rats submitted to the renovascular Goldblatt (two-kidney, one clip) procedure. We inhibited or stimulated this area with the use of drugs such as glycine, L-glutamate, or kynurenic acid. (1) Bilateral microinjection of glycine (100 nmol, 200 nL, n = 13) into the RVLM of hypertensive rats produced a decrease in mean arterial blood pressure (MAP) from 177.2 +/- 29.3 to 102.3 +/- 20.9 mm Hg (P < .05), which was similar to the decrease produced by intravenous administration of hexamethonium. The inhibition of RVLM with glycine in normotensive rats produced a decrease in MAP from 106 +/- 17.1 to 59.7 +/- 7.3 mm Hg (P < .05, n = 9). (2) An impressive increase in MAP from 153.3 +/- 16.3 to 228 +/- 34.9 mm Hg (P < .05) occurred in hypertensive rats after microinjection of L-glutamate (50 nmol, 200 nL, n = 6) into the RVLM. The same procedure caused a significant but less intense increase in MAP from 105 +/- 13.8 to 148.3 +/- 24.9 mm Hg in normotensive rats (P < .05, n = 6). (3) A decrease in MAP from 151.6 +/- 25.3 to 96.8 +/- 22.5 mm Hg occurred in hypertensive rats after microinjection of the broad-spectrum glutamate antagonist kynurenic acid (4 nmol, 200 nL, n = 6) into the RVLM, whereas the same procedure did not change MAP in normotensive animals (n = 6). Heart rate was not significantly affected in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Rostral ventrolateral medulla : A source of sympathetic activation in rats subjected to long-term treatment with L-NAME.

The major aim of the present study was to evaluate the role of the rostral ventrolateral medulla (RVLM) in the maintenance of hypertension in rats subjected to long-term treatment with N(G)-nitro-L-arginine methyl ester (L-NAME) (70 mg/kg orally for 1 week). We inhibited or stimulated RVLM neurons with the use of drugs such as glycine, L-glutamate, or kynurenic acid in urethane-anesthetized rats (1.2 to 1.4 g/kg IV). Bilateral microinjection of glycine (50 nmol, 100 nL) into the RVLM of hypertensive rats produced a decrease in mean arterial blood pressure (MAP) from 158+/-4 to 71+/-4 mm Hg (P<0.05), which was similar to the decrease produced by intravenous administration of hexamethonium. In normotensive rats, glycine microinjection reduced MAP from 106+/-4 to 60+/-3 mm Hg (P<0.05). Glutamate microinjection into the RVLM produced a significant increase in MAP in both hypertensive rats (from 157+/-3 to 201+/-6 mm Hg) and normotensive rats (from 105+/-5 to 148+/-9 mm Hg). No change in MAP was observed in response to kynurenic acid microinjection into the RVLM in either group. These results suggest that hypertension in response to long-term L-NAME treatment is dependent on an increase in central sympathetic drive, mediated by RVLM neurons. However, glutamatergic synapses within RVLM are probably not involved in this response.

Importance of glycinergic and glutamatergic synapses within the rostral ventrolateral medulla for blood pressure regulation in conscious rats.

In this study we used a method that permits bilateral or unilateral microinjections of drugs into the rostral ventrolateral medulla (RVLM) of conscious, freely moving rats. There is only limited information about how sympathetic vasomotor tone is maintained by premotor RVLM neurons in conscious animals. It has long been known that glycine microinjection into the RVLM region leads to a decrease in blood pressure (BP) in anesthetized animals. In the present study we show that both unilateral and bilateral microinjection of glycine at the same dose used for anesthetized rats (50 nmol, 50 nL) into the RVLM increases BP in conscious animals. A similar response was also observed when the excitatory amino acid L-glutamate was microinjected into the RVLM. The microinjection of kynurenic acid into the RVLM did not change the basal level of BP but blocked the increase in BP after glycine or glutamate microinjection. A decrease in BP was only observed when low doses of glycine were used (1 to 10 nmol). We conclude that, in conscious animals, the hypertension occurring in response to high doses of glycine into the RVLM is dependent on glutamatergic synapses within the RVLM. A decrease in BP observed when low doses of glycine were used shows that in conscious animals, the RVLM, in association with other premotor neurons, is probably responsible for the maintenance of sympathetic vasomotor tone, because glycine is less effective in decreasing BP under these circumstances than in anesthetized animals.

Cardiovascular effects produced by micro-injection of angiotensin-(1-7) on vasopressor and vasodepressor sites of the ventrolateral medulla.

In this study, we determined the cardiovascular effects produced by micro-injection of the heptapeptide Angiotensin-(1-7) [Ang-(1-7)] into the rat ventrolateral medulla (VLM). Micro-injection of Ang-(1-7) into the rostral VLM and the caudal pressor area of the VLM produced significant increases in arterial pressure, comparable to that observed with micro-injection of Ang II. The changes in arterial pressure were associated with more variable changes in heart rate (HR) (usually tachycardia). On the other hand, micro-injection of Ang-(1-7) into the caudal depressor area induced decreases in arterial pressure and HR. The results suggest that, besides Ang II, Ang-(1-7) is involved in the mediation of the cardiovascular actions of the renin-angiotensin system in the VLM.

Cardiovascular and respiratory responses to microinjection of L-glutamate into the caudal pressor area in conscious and anesthetized rats.

The role of the caudal pressor area (CPA) in the maintenance of vasomotor tonus in anesthetized and decerebrate animals has been clearly established. In conscious animals, however, the participation of CPA in the cardiovascular control remains to be fully elucidated. In the present study, unilateral L-glutamate (L-Glu) (10 and/or 20 nmol/70 nl) microinjection into CPA, in conscious male Wistar rats (250-280 g) caused a significant increase in mean arterial blood pressure (MAP; control: 112 +/- 1.9 mmHg; after 20 nmol L-Glu: 139 +/- 4.5 mmHg, N = 12, P<0.05) and respiratory rate (control: 81 +/- 3.5 breaths/min; after 10 nmol L-Glu: 92 +/- 3 breaths/min, P<0.05; after 20 nmol L-Glu: 104 +/- 5 breaths/min, N = 6, P<0.05). The subsequent anesthesia with urethane caused a significant increase in basal respiratory frequency (conscious: 81 +/- 3.5 breaths/min; under urethane: 107 +/- 1.3 breaths/min, N = 6, P<0.05). Anesthesia also significantly attenuated L-Glu-evoked pressor (conscious: DeltaMAP = +27 mmHg; anesthetized: DeltaMAP = +18 mmHg, P<0.05) and respiratory responses. These results suggest that glutamatergic receptors in the CPA are involved in cardiovascular and respiratory modulation in conscious rats.

Cardiovascular responses to microinjections of GABA or anesthetics into the rostral ventrolateral medulla of conscious and anesthetized rats.

The rostral ventrolateral medulla (RVLM) contains neurons involved in tonic and reflex control of arterial pressure. We describe the effects of gamma-aminobutyric acid (GABA) and anesthetics injected into the RVLM of conscious and urethane (1.2 g/kg, iv) anesthetized Wistar rats (300-350 g). In conscious rats, bilateral microinjection of GABA (50 nmol/200 nl) induced a small but significant decrease in blood pressure (from 130 +/- 3.6 to 110 +/- 5.6 mmHg, N = 7). A similar response was observed with sodium pentobarbital microinjection (24 nmol/200 nl). However, in the same animals, the fall in blood pressure induced by GABA (from 121 +/- 8.9 to 76 +/- 8.8 mmHg, N = 7) or pentobarbital (from 118 +/- 4.5 to 57 +/- 11.3 mmHg, N = 6) was significantly increased after urethane anesthesia. In contrast, there was no difference between conscious (from 117 +/- 4.1 to 92 +/- 5.9 mmHg, N = 7) and anesthetized rats (from 123 +/- 6.9 to 87 +/- 8.7 mmHg, N = 7) when lidocaine (34 nmol/200 nl) was microinjected into the RVLM. The heart rate variations were not consistent and only eventually reached significance in conscious or anesthetized rats. The right position of pipettes was confirmed by histology and glutamate microinjection into the RVLM. These findings suggest that in conscious animals the RVLM, in association with the other sympathetic premotor neurons, is responsible for the maintenance of sympathetic vasomotor tone during bilateral RVLM inhibition. Activity of one or more of these premotor neurons outside the RVLM can compensate for the effects of RVLM inhibition. In addition, the effects of lidocaine suggest that fibers passing through the RVLM are involved in the maintenance of blood pressure in conscious animals during RVLM inhibition.

Changes in GABAergic inputs in the paraventricular nucleus maintain sympathetic vasomotor tone in chronic heart failure.

The paraventricular nucleus (PVN) of the hypothalamus is an important region of the brain involved in the regulation of sympathetic vasomotor tone. Accumulating evidence supports the idea that a change in hypothalamic γ-aminobutyric acid (GABA)-ergic inhibitory and glutamatergic excitatory inputs contribute to the exacerbated sympathetic drive in chronic heart failure (HF). The purpose of this study was to determine whether a possible imbalance between glutamatergic and GABAergic inputs to the PVN contributes to increased sympathetic outflow in HF in two different sympathetic territories. Renal (RSNA) and splanchnic sympathetic nerve activity (SSNA), mean arterial blood pressure (MAP) and heart rate were recorded from urethane-anesthetized HF or sham rats. The NMDA-glutamate and GABA-A receptor densities within the PVN were quantified in HF and sham rats by autoradiography. Bilateral microinjection of kynurenic acid (4nmol) into the PVN decreased MAP and RSNA and SSNA in HF but not in sham rats. Furthermore, in response to GABA-A blockade in the PVN by bicuculline (400 pmol), hypertension and SSNA were reduced in HF compared to sham. The quantification of ionotropic NMDA receptors and GABA-A receptors in the PVN showed a significant reduction of GABA-A in HF rats; however, the NMDA density in the PVN did not differ between groups. Thus, this study provides evidence that the sympathoexcitation is maintained by an imbalance between GABAergic and glutamatergic inputs in the PVN in HF. The reduced GABAergic input results in relatively augmented glutamatergic actions in the PVN of HF rats.

Cardioprotective effect of ornitho-kinin in an anesthetized, open-chest chicken model of acute coronary occlusion.

The generation of bradykinin (BK; Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) in blood and kallidin (Lys-BK) in tissues by the action of the kallikrein-kinin system has received little attention in non-mammalian vertebrates. In mammals, kallidin can be generated by the coronary endothelium and myocytes in response to ischemia, mediating cardioprotective events. The plasma of birds lacks two key components of the kallikrein-kinin system: the low molecular weight kininogen and a prekallikrein activator analogous to mammalian factor XII, but treatment with bovine plasma kallikrein generates ornitho-kinin [Thr6,Leu8]-BK. The possible cardioprotective effect of ornitho-kinin infusion was investigated in an anesthetized, open-chest chicken model of acute coronary occlusion. A branch of the left main coronary artery was reversibly ligated to produce ischemia followed by reperfusion, after which the degree of myocardial necrosis (infarct size as a percent of area at risk) was assessed by tetrazolium staining. The iv injection of a low dose of ornitho-kinin (4 microg/kg) reduced mean arterial pressure from 88 +/- 12 to 42 +/- 7 mmHg and increased heart rate from 335 +/- 38 to 402 +/- 45 bpm (N = 5). The size of the infarct was reduced by pretreatment with ornitho-kinin (500 microg/kg infused over a period of 5 min) from 35 +/- 3 to 10 +/- 2% of the area at risk. These results suggest that the physiological role of the kallikrein-kinin system is preserved in this animal model in spite of the absence of two key components, i.e., low molecular weight kininogen and factor XII.

Role of the caudal pressor area in the regulation of sympathetic vasomotor tone.

It is well known that the ventrolateral medulla contains neurons involved in the tonic and reflex control of the cardiovascular system. Two regions within the ventrolateral medulla were initially identified: the rostral ventrolateral medulla (RVLM) and the caudal ventrolateral medulla (CVLM). Activation of the RVLM raises arterial blood pressure and sympathetic nerve activity, and activation of the CVLM causes opposite effects. The RVLM premotor neurons project directly to sympathetic preganglionic neurons and are involved in the maintenance of resting sympathetic vasomotor tone. A significant proportion of tonic activity in the RVLM sympathetic premotor neurons is driven by neurons located in a third region of the ventrolateral medulla denominated caudal pressor area (CPA). The CPA is a pressor region located at the extreme caudal part of the ventrolateral medulla that appears to have an important role controlling the activity of RVLM neurons. In this brief review, we will address the importance of the ventrolateral medulla neurons for the generation of resting sympathetic tone related to arterial blood pressure control focusing on two regions, the RVLM and the CPA.

Induction of cell migration and activation in mice by the freshwater sponge Drulia uruguayensis Bonetto & Ezcurra de Drago, 1968 (Porifera: Metaniidae)

Freshwater sponges are abundant in the Amazon region and they have been known to cause dermatitis (acute inflammation) since the beginning of the 20th century. To determine whether additional constituents, besides their body spicules, cause dermatological reactions in humans, an experimental study was developed and carried out using mice and Drulia uruguayensis prepared in three different forms: intact sponges (IS), macerated sponges (MS) or isolated spicules - megascleres (ISM). The cells most commonly involved in inflammatory reactions (mast cells, eosinophils and neutrophils), as well as intraepithelial lymphocytes and degranulated mast cells, were counted so that they could be used as parameters to determine which of the sponge preparations induced the greatest reaction. The effects of the sponge on the skin were then determined by histological analysis. The results obtained showed that IS caused the greatest inflammatory reaction (p = 0.000005), activating mainly mast cells (p = 0.0018). The histopathological analysis revealed a slight loss of continuity of the epidermis when ISM or IS were applied. These findings allow us to conclude that a structurally intact sponge can cause a greater inflammatory reaction in the first contact because of its ability to perforate the skin and allow inflammatory agents to enter. Other proteins present in dried sponge bodies could induce allergic but not toxic responses (in contact with the entire sponge, a large number of pharmacologically inert proteins may be introduced, with a potential allergen).