Increase In Mean Arterial Blood Pressure Research Articles

Increasing Mean Arterial Blood Pressure and Heart Rate With Catecholaminergic Drugs Does Not Improve the Microcirculation in Children With Congenital Diaphragmatic Hernia

To study whether dopamine, norepinephrine, and epinephrine improve not only mean arterial blood pressure and heart rate but also microcirculatory perfusion in children with congenital diaphragmatic hernia. Prospective observational cohort study from November 2009 to July 2012. ICU of a level III university children's hospital. Twenty-eight consecutive congenital diaphragmatic hernia newborns of whom seven did not receive any catecholaminergic support and 21 received dopamine as the drug of first choice. Fourteen of the latter also received either norepinephrine or epinephrine in addition to dopamine. Twenty-eight healthy neonates, matched for gestational age, postnatal age, and gender, served as controls. None. Data were obtained before and after dopamine start and before and after norepinephrine or epinephrine start in case it was given. For the congenital diaphragmatic hernia without catecholaminergic support, data were obtained at admission days 1 and 2 and for the controls on day 1 of life. The buccal microcirculation was studied using Sidestream Dark Field imaging. Also macrocirculatory, respiratory, and biochemical variables were collected. Mean arterial blood pressure had improved after dopamine start, whereas the microcirculation had not. After the start of either norepinephrine or epinephrine, both blood pressure and heart rate had increased. However, the microcirculation failed to improve again. The microcirculation in the healthy controls was better than that in the congenital diaphragmatic hernia patients with catecholaminergic support. After cutoff values for abnormal microcirculation had been defined, abnormal microcirculation after dopamine start predicted the need for additional catecholaminergic support (area under the curve, 0.74-0.88; sensitivity, 77-77%; specificity, 69-77%). Likewise, microcirculatory impairment was associated with the need for extracorporeal membrane oxygenation. Catecholaminergic drug support with dopamine, norepinephrine, and/or epinephrine improved macrocirculatory function but did not improve the microcirculation in neonates with congenital diaphragmatic hernia. The microcirculation was not only impaired but it also predicted poor outcome.

Angiotensin converting enzyme inhibition reduces cardiovascular responses to acute stress in myocardially infarcted and chronically stressed rats.

Previous studies showed that chronically stressed and myocardially infarcted rats respond with exaggerated cardiovascular responses to acute stress. The present experiments were designed to elucidate whether this effect can be abolished by treatment with the angiotensin converting enzyme (ACE) inhibitor captopril. Sprague Dawley rats were subjected either to sham surgery (Groups 1 and 2) or to myocardial infarction (Groups 3 and 4). The rats of Groups 2 and 4 were also exposed to mild chronic stressing. Four weeks after the operation, mean arterial blood pressure (MABP) and heart rate (HR) were measured under resting conditions and after application of acute stress. The cardiovascular responses to the acute stress were determined again 24 h after administration of captopril orally. Captopril significantly reduced resting MABP in each group. Before administration of captopril, the maximum increases in MABP evoked by the acute stressor in all (infarcted and sham-operated) chronically stressed rats and also in the infarcted nonchronically stressed rats were significantly greater than in the sham-operated rats not exposed to chronic stressing. These differences were abolished by captopril. The results suggest that ACE may improve tolerance of acute stress in heart failure and during chronic stressing.

Baroreceptor and Chemoreceptor Reflex Contribution in Cardiovascular Changes during Exercise

During exercise, both baroreceptors and chemoreceptors contribute in bringing about the cardiovascular changes, but less is documented about the contribution made by either of these mechanisms. The purpose of the present study was to demonstrate the differential effects of baroreceptors and chemoreceptors on cardiovascular parameters during exercise. Twelve healthy individuals were subjected to exercise maneuver on stationary cycling machine. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and electrocardiogram (ECG) were recorded during rest and immediately after exercise. Heart rate (HR) and heart rate variability (HRV) was computed from ECG. SBP, DBP, mean arterial blood pressure (MABP) and HR significantly increased due to exercise. Increase in SBP, DBP, Pulse pressure (PP), MABP and HR were more pronounced when chemoreceptor influence was not considered as against when changes due to both baroreceptors and chemoreceptors were considered. The HRV analysis reflected increase in the low-frequency (LF) power % and decrease in high-frequency (HF) power % along with reduction in LF/HF ratio due to exercise, but these changes were statistically not significant. Baroreceptors through baroreflex mechanism overall increase the CVS parameters. The novel finding in this study was the opposing action of chemoreceptor mechanism to that of baroreceptor mechanism in cardiovascular homeostasis during exercise.

Abstract 474: High Salt Diet Modulates Ca 2 +-Sensing Receptor and Cytochrome P450 Isoform Expression in Mesenteric Arteries in Dahl Salt-Sensitive Rats

The Ca 2+ -sensing receptor (CaSR) mediates relaxation of isolated, phenylephrine-contracted mesenteric arteries, which express the receptor in the sensory network. We tested the hypothesis that high salt alters the expression of CaSR and its CYP enzymes downstream of the receptor in salt-sensitive hypertension. Dahl salt−sensitive (DS) and Dahl salt-resistant (DR) rats were placed on an 8% NaCl diet (HS) for 1, 2, and 4 weeks. Using tail cuff plethysmyography, blood pressures were measured before and after HS diet treatment. Our results show a significant increase in blood pressure in DS animals on HS diet (Control : 116 ± 4.8 mmHg; 1 week HS: 164.4 ± 8.7 mmHg; 2 weeks HS: 175.1 ± 7.2 mmHg; p < 0.05 , ANOVA). Western blot analysis of proteins extracted from mesenteric arteries showed an increase in CaSR, CYP1A1, and CYP2J2 expression in DS rats on HS diet, but not in arteries from DR rats on the same diet. The data show that HS increased mean arterial blood pressure, as expected, and increased the expression of the mature form of the CaSR while decreasing expression of the immature form. Increased CYP isoform expression was observed as well, however, these changes did not reduce blood pressure. These new findings suggest an abnormality in CaSR activity in salt −sensitive hypertension, which may provide a molecular target for anti-hypertensive therapies.

Intracerebroventricular injection of stresscopin-related peptide enhances cardiovascular function in conscious rats

Stresscopin-related peptide (SRP), which is a member of the corticotropin-releasing factor (CRF) family, is a high-affinity ligand for the type 2 corticotropin-releasing factor receptor (CRF-R2) and is involved in stress-coping responses. Central treatment with SRP suppresses food intake, delays gastric emptying and decreases heat-induced edema, but the effects of central administration of SRP on the cardiovascular system are unclear. Here we examined the effects of intracerebroventricular (i.c.v.) administration of SRP on cardiovascular function, and compared the cardiovascular effects of SRP and stresscopin (SCP). Our results showed that i.c.v. administration of SRP (0.5nmol) increased mean arterial blood pressure (MABP) and heart rate (HR), but failed to increase plasma norepinephrine and epinephrine levels. Compared with an equivalent dose of SCP, the area under the curve (AUC) values for the changes in MABP and HR were significantly smaller with SRP, indicating that the cardiovascular effects of SRP were weaker than those mediated by SCP. Pre-treatment with a selective CRF-R2 antagonist, antisauvagine-30 (4nmol, i.c.v.) abolished the SRP and SCP induced changes in MABP and HR. These results indicate that central administration of SRP induces a weaker enhancement of cardiovascular function through CRF-R2 than that induced by SCP and that these effects are mediated without increasing plasma norepinephrine and epinephrine levels.

Effect of healthy aging on renal vascular responses to local cooling and apnea

Sympathetically mediated renal vasoconstriction may contribute to the pathogenesis of hypertension in older adults, but empirical data in support of this concept are lacking. In 10 young (26 ± 1 yr) and 11 older (67 ± 2 yr) subjects, we quantified acute hemodynamic responses to three sympathoexcitatory stimuli: local cooling of the forehead, cold pressor test (CPT), and voluntary apnea. We hypothesized that all stimuli would increase mean arterial blood pressure (MAP) and renal vascular resistance index (RVRI) and that aging would augment these effects. Beat-by-beat MAP, heart rate (HR), and renal blood flow velocity (from Doppler) were measured in the supine posture, and changes from baseline were compared between groups. In response to 1°C forehead cooling, aging was associated with an augmented MAP (20 ± 3 vs. 6 ± 2 mmHg) and RVRI (35 ± 6 vs. 16 ± 9%) but not HR. In older adults, there was a positive correlation between the cold-induced pressor response and forehead pain (R = 0.726), but this effect was not observed in young subjects. The CPT raised RVRI in both young (56 ± 13%) and older (45 ± 8%) subjects, but this was not different between groups. Relative to baseline, end-expiratory apnea increased RVRI to a similar extent in both young (46 ± 14%) and older (41 ± 9%) subjects. During sympathetic activation, renal vasoconstriction occurred in both groups. Forehead cooling caused an augmented pressor response in older adults that was related to pain perception.

ESTROGEN‐RESPONSIVE NEURONS IN THE MEDIAL AMYGDALA PREVENT STRESS‐INDUCED HYPERTENSION

BackgroundHypertension is the leading cause of cardiovascular disease worldwide. The etiology of essential hypertension is unknown. Psychological stress contributes to development of hypertension in humans. Estrogen has been shown to prevent stress‐induced hypertension in rodents with unknown mechanisms. Amygdala neurons have been implicated in controlling blood pressure. Abundant estrogen receptors, including estrogen receptor‐α (ERα), are expressed in the medial amygdala (MeA). Thus, we hypothesize that ERα expressed by MeA neurons mediates the anti‐hypertensive effects of estrogen during stress.MethodsWe use the Cre‐LoxP system to remove ERα from specific MeA neurons in mice (ERαlox/lox/SIM1‐Cre). Female ERαlox/lox/SIM1‐Cre mice and controls (ERαlox/lox) were subjected to bilateral ovariectomy (OVX), given a vehicle (V) or 17‐β‐Estradiol pellet (E2), and inserted with telemetry probes on day one. After a seven‐day recovery, blood pressure was recorded for 3 hours to establish baseline and then mice were subjected to 1 hour stress restraint.ResultsERαlox/lox OVX + V mice showed increased mean arterial blood pressure (MAP) and systolic arterial blood pressure (SAP) in response to stress, whereas this stress‐induced hypertension was blunted in ERαlox/lox OVX + E mice. Interestingly, ERαlox/lox/SIM1‐Cre OVX + E and OVX + V group both showed increased MAP and SAP in response to stress.ConclusionsOur results suggest that ERα in the MeA is required to mediate estrogenic actions to prevent stress‐induced hypertension.

Branched-chain amino acids alleviate nonalcoholic steatohepatitis in rats

Nonalcoholic steatohepatitis (NASH) is a prevalent disease in countries around the world. The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine cannot be synthesized by the body and have been shown to promote muscle buildup; thus, it is logical to suggest that BCAAs can reduce fat deposition in the body. We used gonadectomized rats fed a high-fat diet to investigate the effects of BCAAs on lipid metabolism over an 8-week experimental period. Body composition, tissue histology, plasma lipid indices, and hormone levels were examined. We demonstrated that the body weights of rats were not significantly decreased but the mesenteric fat was significantly decreased (p < 0.05) in BCAA-treated rats. In addition, BCAAs decreased plasma lipid levels and fat deposition in the liver. At week 4, when the untreated rats displayed macrovesicular steatosis, BCAA-treated rats had only macrovesicular droplets in their hepatocytes. At week 8, when the untreated rat livers displayed profound inflammation and cirrhosis, BCAA-treated rat livers remained in the macrovesicular stage of steatosis. BCAAs induced higher blood glucose and plasma insulin levels (p < 0.05). BCAAs also improved liver blood flow by increasing mean arterial blood pressure and decreasing portal pressure, which helped delay the change in blood flow pattern to that of cirrhosis. BCAAs also induced the skeletal muscle to express higher levels of branched-chain α-keto acid dehydrogenase E1α, which indicates an enhanced metabolic capacity of BCAAs in muscle tissue. This study clearly demonstrates the effects of BCAAs on the amelioration of fat deposition in rats fed a high-fat diet.

Increasing mean arterial blood pressure in sepsis: effects on fluid balance, vasopressor load and renal function

IntroductionThe objective of this study was to evaluate the effects of two different mean arterial blood pressure (MAP) targets on needs for resuscitation, organ dysfunction, mitochondrial respiration and inflammatory response in a long-term model of fecal peritonitis.MethodsTwenty-four anesthetized and mechanically ventilated pigs were randomly assigned (n = 8/group) to a septic control group (septic-CG) without resuscitation until death or one of two groups with resuscitation performed after 12 hours of untreated sepsis for 48 hours, targeting MAP 50-60 mmHg (low-MAP) or 75-85 mmHg (high-MAP).ResultsMAP at the end of resuscitation was 56 ± 13 mmHg (mean ± SD) and 76 ± 17 mmHg respectively, for low-MAP and high-MAP groups. One animal each in high- and low-MAP groups, and all animals in septic-CG died (median survival time: 21.8 hours, inter-quartile range: 16.3-27.5 hours). Norepinephrine was administered to all animals of the high-MAP group (0.38 (0.21-0.56) mcg/kg/min), and to three animals of the low-MAP group (0.00 (0.00-0.25) mcg/kg/min; P = 0.009). The high-MAP group had a more positive fluid balance (3.3 ± 1.0 mL/kg/h vs. 2.3 ± 0.7 mL/kg/h; P = 0.001). Inflammatory markers, skeletal muscle ATP content and hemodynamics other than MAP did not differ between low- and high-MAP groups. The incidence of acute kidney injury (AKI) after 12 hours of untreated sepsis was, respectively for low- and high-MAP groups, 50% (4/8) and 38% (3/8), and in the end of the study 57% (4/7) and 0% (P = 0.026). In septic-CG, maximal isolated skeletal muscle mitochondrial Complex I, State 3 respiration increased from 1357 ± 149 pmol/s/mg to 1822 ± 385 pmol/s/mg, (P = 0.020). In high- and low-MAP groups, permeabilized skeletal muscle fibers Complex IV-state 3 respiration increased during resuscitation (P = 0.003).ConclusionsThe MAP targets during resuscitation did not alter the inflammatory response, nor affected skeletal muscle ATP content and mitochondrial respiration. While targeting a lower MAP was associated with increased incidence of AKI, targeting a higher MAP resulted in increased net positive fluid balance and vasopressor load during resuscitation. The long-term effects of different MAP targets need to be evaluated in further studies.

Effect of combination of renin inhibitor and Mas-receptor agonist in DOCA–salt-induced hypertension in rats

To investigate the combined effect of aliskiren, a renin inhibitor, and AVE 0991, a Mas-receptor agonist, in experimental hypertension (HT) in rats. HT was produced by administration of deoxycorticosterone acetate (DOCA) and mean arterial blood pressure (MABP) was assessed by tail-cuff method. Treatments were started from 4th week onwards and were continued for 9 days. A significant increase in MABP was noted after 1 week in DOCA control rats, as compared with the base line value. A stable HT developed after 4 weeks of DOCA administration. Treatments with aliskiren and AVE 0991 alone, dose-dependently decreased MABP in DOCA-treated rats. Further, combination of low doses of aliskiren and AVE 0991 significantly reduced MABP, as compared with DOCA control rats and with either drug alone in low doses. It may be concluded that treatment with aliskiren produced down-regulation of both harmful Ang II-AT1-receptor and survival Ang(1-7)/Mas-receptor axis of RAAS. Treatment with combination of low doses of aliskiren and AVE 0991, for the first time, has been shown to produce synergistic blood pressure lowering effect. Therefore, combination of renin inhibitor with Mas-receptor agonist may prove beneficial for the treatment of hypertensive patients.

Abstract 35: Transplantation of Mesenchymal Stem Cells into the Renal Medulla Attenuated Salt-sensitive Hypertension in Dahl S Rat

Transplantation of mesenchymal stem cells (MSCs) has been employed as a therapeutic strategy for many different diseases. We have recently shown that there is a stem cell dysfunction in the renal medulla that may contribute to the development of salt-sensitive hypertension in Dahl S rats. The present study tested the hypothesis that transplantation of MSCs into the renal medulla improves salt-sensitive hypertension in Dahl S rats. Rat adult MSCs were obtained from Texas A&amp;M Health Science Center, ex-vivo expanded and infused (5 million cells) into the renal medulla in uninephrectomized Dahl S rats, which were then treated with low salt (LS, 0.4% NaCl) or high salt (HS, 8% NaCl) diet for 10 days. Results showed that the mRNA levels of stem cell markers CD133 and CD90 were increased by 60% and 70%, respectively, in the renal medulla in MSC-treated rats compared with control cell-treated rats. HS challenge increased mean arterial blood pressure in control cell-treated animals (from 113.9 ± 3.4 to 153.5 ± 4.8 mmHg), which was significantly attenuated in MSC-treated animals (from 114.1 ± 3.5 to 131.3 ± 2.5 mmHg). Meanwhile, ELISA analysis showed that the levels of pro-inflammatory cytokine interleukin-1β in the renal medulla were remarkably increased in HS-treated rats compared with LS-treated rats, which was blocked in MSC-treated rats (1.81 ± 0.18 ng/mg protein in LS group, 2.84 ± 0.57 in HS +control cell and 1.83 ± 0.35 in HS+MSC). Furthermore, immunostaining showed that the significant increase in immune cell (CD43+) infiltration into the renal medulla in HS control rats was reduced in HS+MSC rats. These results suggest that correction of stem cell dysfunction in the renal medulla attenuated inflammation in this kidney region after HS challenge and improved high salt-induced hypertension in Dahls S rats, which may serve as a therapeutic approach for salt-sensitive hypertension (supported by NIH grant HL89563 and HL106042)

Abstract 112: Organum Vasculosum Lateral Terminalis (OVLT) Contributes to Na+-Induced Sympathoexcitation and Hypertension

High dietary salt intake increases plasma and CSF Na+ concentration to elevate sympathetic nerve activity (SNA) and arterial blood pressure (ABP). Ablation of the anterior ventral 3 rd ventricle (AV3V) region attenuates the elevation in SNA and ABP during acute and chronic salt loading. The AV3V contains numerous hypothalamic nuclei including osmosensitive neurons of the OVLT. The purpose of this study was twofold: 1) to determine whether OVLT neurons mediate the sympathetic and hypertensive effects of central salt loading and 2) to characterize the changes in SNA to different vascular beds and/or end organs. Male Sprague-Dawley rats received an intracerebroventricular (ICV) infusion of 1M NaCl (5ul over 10min) before and after lesion of AV3V (n≥4) or OVLT (n=7). ICV infusion of NaCl increased mean ABP (8.9±1.0mmHg) and lumbar SNA (26.4±3.6%) but decreased renal (-18.6±2.3%) and splanchnic SNA (-10.6±2.3%). Electrolytic lesion of the AV3V region attenuated this Na+-induced increase in ABP (8.9±1.0 vs 1.7±0.4mmHg, p=0.001) and lumbar SNA(26.4±3.6% vs 8.0±1.9%, p=0.001) but did not alter the inhibition of renal SNA (-18.6±2.3% vs -19.2±3.5%, p&gt;0.8) and splanchnic SNA (-10.6.±2.3% vs -8.2±1.7%, p&gt;0.4). ICV infusion of 1M NaCl produced similar increases in ABP, lumbar, renal and splanchnic SNA between control versus sham-lesion animals. Selective lesion of the OVLT attenuated the Na+-induced increase in ABP (10.4±2.0 vs 5.8±0.8mmHg, p&lt;0.05) and lumbar SNA (31.8±3.7 vs 16.3±2.3% p&lt;0.02). OVLT ablation also attenuated the inhibition of renal SNA (-18.2±2.6 vs -7.5±2.4%, p&lt;0.02) and tended to lessen the inhibition of splanchnic SNA (-8.8±1.9 vs -4.0±1.1%, p=0.065). Even though both AV3V and OVLT lesions attenuated the increase in lumbar SNA and ABP in response to central Na+ load, the magnitude of the attenuation was significantly greater in AV3V versus OVLT-lesioned animals (p&lt;0.05). Taken together, these findings suggest that acute increases in CSF Na+ activate OVLT neurons to selectively increase lumbar SNA and ABP. However, our findings also suggest that structures other than the OVLT participate in the sympathoexcitatory response to increased CSF Na+.

Glucose and blood pressure lowering effects of Pycnogenol® are inefficient to prevent prolongation of QT interval in experimental diabetic cardiomyopathy

Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by increased duration of QT interval. Although the mechanism is unknown, it is widely believed that the reduction of hyperglycaemia might prevent such alterations. To test this hypothesis, we used the standardized extract of French pine bark – Pycnogenol® (PYC) with hypoglycaemic and antioxidant properties in 8–9 week old rats with experimentally (streptozotocin) induced diabetes mellitus (DM). PYC was administered orally for 6 weeks in three different doses (10, 20, and 50mg/kg b.w., resp.). Experimental DM was manifested by hyperglycaemia (four to six-fold increase in plasma glucose concentration; p<0.05) and significantly increased mean arterial blood pressure (by 19%; p<0.05) measured using catheterization of carotid artery in vivo. Both abnormalities were dose-dependently reduced by PYC. In addition, diabetic cardiomyopathy was associated with a significant increase in left ventricular weight to body weight ratio (by 21%; p<0.05) and a significant decrease of the width of cardiomyocytes (by 23%; p<0.05) indicating cardiac edema on the one side, and hypotrophy of cardiomyocytes on the other. Both of these changes were not affected by PYC. Consequently to metabolic and hemodynamic alterations, significant prolongation of QT interval (by 20%; p<0.05) was present in diabetic rats, however, PYC failed to correct it. Conclusively, PYC fails to correct QT prolongation in spite of dose-dependent reduction of glycaemia and high blood pressure in streptozotocin-induced diabetic cardiomyopathy.

Lung ventilation is an effector of the baroreflex in the cane toad (Rhinella marina)

Lung ventilation plays an important role for regulating lymph flux in anurans by changing the compliance of lymph sacs that surround the lungs during changes in lung volume. Because lymph mobilization in anurans is dependent upon blood volume/pressure status, we hypothesized that lung ventilation, like cardiac and lymph heart effectors, is also an effector of the baroreflex. We tested this hypothesis by measuring lung ventilation frequency (fR) and heart rate (HR) while increasing mean arterial blood pressure (MAP) with phenylephrine (Phe; 0.05–1.0 mg/kg, i.v.) and decreasing MAP with sodium nitroprusside (SNP; 0.05–1.0 mg/kg, i.v.). Decreasing MAP with SNP resulted in a significant increase in fR by an average of 12 breaths min−1 while increasing MAP with Phe decreased fR by an average of 4 breaths min−1. The slope of the baroreflex gain (ΔHR/ΔMAP; beats min−1 kPa−1) for combined Phe and SNP injections was −3.9 ± 0.9 (r2 =0.54; P&lt;0.001) and was similar to the slope of the relationship between ΔfR and ΔMAP (−5.2 ± 0.8; r2 = 0.69; P&lt;0.001). These results suggest that lung ventilation is regulated by MAP, in addition to blood gases and pH, and is an effector of the baroreflex. Supported by NSF‐IOS 0843082.

Assessment of chronic sympathetic nerve recording using Data Sciences International telemetry

The ability to assess sympathetic nervous system function in conscious animals has been hampered by the inability to chronically record sympathetic nerve activity (SNA). The present study tested the newly developed F50‐W‐F2 transmitter from Data Sciences. Male Sprague‐Dawley rats (300–400 g) were implanted with a PA‐C40 transmitter to measure arterial blood pressure, and a F50‐W‐F2 transmitter to record lumbar SNA. After 5 day recovery, &gt;70% of animals had stable SNA recordings characterized by pulse‐synchronous bursts. Animals with viable SNA at Day 6 continued to remain viable for several weeks (average 34±6 days) including signals that persisted in 2 animals for 80+ days. To test the responsiveness of the transmitters, animals were water deprived for 48 hours. Water deprivation significantly increased mean arterial blood pressure (12±2 mmHg), rectified SNA (41±6%), and lumbar burst frequency (4±1 Hz). When water was provided, values returned to baseline levels within 24 hours. In subsequent weeks, the magnitude of the responses was reproducible. These findings suggest that the F50‐W‐F2 radiotransmitter for SNA is reliable and easy to integrate into existing platforms. The implantation success rate and long‐term viability suggest these transmitters may provide a distinct advantage over conventional approaches to study sympathetic function.

Simvastatin but not pravastatin reduces the hypertensive response to intracerebroventricularly infused angiotensin II

Several lines of evidence suggest that beneficial effects of statins may depend in part on their interaction with angiotensin peptides. For example, recently we have found that simvastatin reduces the hypertensive response to intracerebroventricularly (icv) infused angiotensin II (Ang II) in rats. In the preset study, we checked whether orally given pravastatin affects the hypertensive response to icv infused Ang II in the same manner as does simvastatin. We maintained Sprague Dawley rats on either tap water (control) or water containing simvastatin or pravastatin for four weeks. Subsequently, we measured arterial blood pressure and heart rate at baseline and after icv infusions of Ang II. We found no significant difference between the groups in mean arterial blood pressure (MABP) and heart rate at baseline. ICV infusion of 10 ng of Ang II caused a significant increase in MABP in all the groups. Rats treated with simvastatin showed significantly smaller hypertensive responses to icv Ang II than controls and pravastatin treated rats. In conclusion, the study shows that simvastatin but not pravastatin affects the hypertensive response to icv infused Ang II. These may be caused by differences in penetration through the blood‐brain barrier between the statins and their metabolites. The study was supported by the Polish Ministry of Science and Higher Education, Iuventus plus grant.

Differential Effects of Angiotensin II on Intra-Renal Hemodynamics in Rats; Contribution of Prostanoids, NO and K&amp;lt;sup&amp;gt;+&amp;lt;/sup&amp;gt; Channels

Many agents are known to cause qualitative and quantitative differences in intrarenal blood flow. This study tested the hypothesis that angiotensin II (AII) evokes a differential effect on cortical (CBF) and medullary blood flow (MBF) and that AT2 receptor mediates AII-induced increase in renal MBF by mechanisms related to nitric oxide (NO) and prostanoids. AII (100, 300 and 1000 ng/kg/min) increased mean arterial blood pressure (MABP) by 24% ± 7% (p G nitro-L-arginine (L-NNA), an inhibitor of NO synthase (100 mg/L in drinking water) enhanced AII effects on MABP (169 ± 75, p ATP channel blocker, did not affect intra-renal hemodynamics elicited by AII. Blockade of AT2 receptors with PD123319 (50 μg/kg/min) did not change basal or AII-induced changes MABP or CBF but blunted AII-induced increase in MBF by 60% ± 11 % (p 2 receptor agonist, elicited a reduction in MABP and increases in CBF and MBF that were abolished or attenuated by PD123319. These findings demonstrate that AII elicited differential changes in intrarenal blood flow; an AT1-mediated reduction in CBF but an AT2-mediated increase in MBF. The AT2 receptor-mediated increase in MBF involves guanylase cyclase, NO and dilator prostanoids but not KATP channels.

Oxidative stress mediates cardiac infarction aggravation induced by intermittent hypoxia

We have previously shown that chronic intermittent hypoxia (IH), a component of the obstructive sleep apnea syndrome, increases heart sensitivity to infarction. We investigate here the deleterious mechanisms potentially involved in the IH-induced infarction aggravation, investigating the role of oxidative stress. Male Wistar rats were subjected to chronic IH or normoxia (N). IH consisted of repetitive 1-min cycles (30 s with inspired O2 fraction 5% followed by 30 s normoxia) and was applied for 8 h during daytime, for 14 days. After the 14-day exposure, mean arterial blood pressure (MABP) was higher in the hypoxic compared with the normoxic group. Infarct size, measured on isolated hearts after ischemia-reperfusion, was significantly increased in IH compared with normoxic group (36.0 ± 2.8% vs. 21.8 ± 3.1% for tempol corresponding control groups and 40.3 ± 3.5% vs. 29.4 ± 3.7% for melatonin corresponding control groups). Tempol or melatonin administration during the 14-day IH exposure prevented both IH-induced increase in MABP and infarction aggravation (24.8 ± 2.8% vs. 25.9 ± 4.0% for tempol-treated groups and 32.3 ± 3.2% vs. 34.5 ± 4.2% for melatonin-treated groups). Myocardial oxidative stress was induced by IH, as measured by dihydroethidium (DHE) level and p47-phox expression (the cytosolic protein required for the activation of the NADPH oxidase). This effect was abolished by tempol and melatonin treatments, which were able to normalize DHE level and NADPH expression. In conclusion, oxidative stress appears to mediate the deleterious cardiovascular effects of IH and, in particular, the increased myocardial susceptibility to infarction.

Changes in Serum S100A12 and sRAGE Associated with Improvement of the PaO2/FiO2 Ratio following PMX-DHP Therapy for Postoperative Septic Shock

Background: Endotoxin (Et) adsorption therapy with a column of polymyxin B-immobilized fibers (PMX) is effective in improving the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (PaO₂/FiO₂ ratio) and increasing mean arterial blood pressure (MAP) in sepsis. S100A12 and soluble receptor for advanced glycation end product (sRAGE) are useful as early markers of acute lung injury. Purpose: To investigate the effect of improving the PaO₂/FiO₂ ratio by PMX-direct hemoperfusion (PMX-DHP) on production of S100A12 and sRAGE. Subjects and Methods: Sepsis patients after surgery for perforation of the lower gastrointestinal tract were adopted as the subjects. We retrospectively reviewed the cases of 20 patients on mechanical ventilation and continuous administration of norepinephrine. We recorded PaO₂/FiO₂ ratio, MAP, and norepinephrine doses. S100A12, sRAGE, and Et levels were measured before and after PMX-DHP. Results: The PaO₂/FiO₂ ratio and MAP improved significantly after PMX-DHP (p < 0.05). S100A12 and Et decreased significantly after PMX-DHP (p < 0.05). No differences were observed in sRAGE. Conclusion: S100A12 is useful as a marker that reflected improvement in the PaO₂/FiO₂ ratio after PMX-DHP. We consider PMX-DHP to be useful as adjunctive therapy for sepsis that reduces the Et and corrects the pathology in the early stage.

Forty-Minute Endovascular Aortic Occlusion Increases Survival in an Experimental Model of Uncontrolled Hemorrhagic Shock Caused by Abdominal Trauma

To evaluate the feasibility of aortic balloon catheter occlusion in intra-abdominal hemorrhage. Effects of transfemoral diaphragmatic aortic balloon occlusion (ABO) have been evaluated in 25 pigs. The animals were submitted to incontrollable hemorrhage by a splenic trauma. Group 1 (n = 9) received fluid resuscitation with normal saline (NS) without aortic occlusion; group 2 (n = 8) underwent 60 minutes ABO and NS. Groups 3 (n = 4) and 4 (n = 4) underwent ABO during 40 minutes and 60 minutes, respectively, NS, and splenectomy. Aortic balloon location was adequate in all animals. ABO increased the portion of 2-hour survivors significantly (7/16 vs. 0/9; p = 0.03). ABO increased mean arterial blood pressures (p < 0.05). There was a significant decrease of bleeding and volume of fluid resuscitation (p < 0.05) in ABO groups. Blood potassium and lactate levels at death were significantly higher in groups 2 and 4 compared with those of the control group: 29 ± 0.54 and 6.08 mmol/L ± 0.44 mmol/L versus 4.16 mmol/L ± 0.35 mmol/L (p < 0.02), and 11.39 mmol/L ± 0.37 mmol/L and 9.59 mmol/L ± 1.19 mmol/L versus 6.43 mmol/L ± 0.57 mmol/L (p < 0.001), respectively. There were no significant differences between group 3 and the control group: 4.83 mmol/L ± 0.32 mmol/L versus 6.43 mmol/L ± 0.57 mmol/L and 5.2 mmol/L ± 0.13 mmol/L versus 4.16 mmol/L ± 0.35 mmol/L, respectively. At necropsy, there were no significant differences in terms of visceral (bowel and kidney) ischemia between the different experimental groups. A 40-minute ABO followed by surgical damage control improved survival in this animal model of uncontrolled hemorrhagic shock caused by abdominal trauma. ABO could be considered for the management of severe abdominal trauma.