Significant Increase In Mean Arterial Blood Pressure Research Articles

Pharmacodynamics of propofol and alfaxalone in rattlesnakes (Crotalus durissus)

To characterise the effect of two common induction agents, propofol and alfaxalone, on mean arterial blood pressure (MAP) and heart rate (HR), we equipped 19 adult South American rattlesnakes (Crotalus durissus) with an indwelling arterial catheter approximately 24 h prior to recording of baseline resting values. Then, seven snakes received alfaxalone (15 mg kg−1) intravascularly (IV) through the catheter, while groups two and three (both n = 6) received propofol (15 mg kg−1 IV). The first two groups were not handled, while the group 3 was manually restrained for 2 min for a mock injection of 0.2 ml saline into the ventral tail vein. Baseline HR was similar in all groups and handling caused a significant tachycardia (p = 0.031) in group three. When given IV to undisturbed animals, both propofol and alfaxalone induced a significant increase in HR (p = 0.0022 and p = 0.0045, respectively) lasting approximately 30 min, but with values only significantly exceeding baseline for the first 5 min for propofol and the first 10 min with alfaxalone. Handling caused a significant increase in MAP (p = 0.0313). Propofol did not affect MAP (p = 0.1064), while alfaxalone caused a marked hypertension (although only significant at 2 min; p = 0.031). Manual restraint significantly increases both HR and MAP, which may lead to a masking of true cardiovascular effects of anaesthetic agents.

Sufentanil blunts the myocardial stress induced by tracheal intubation in older adult patients with coronary heart disease better than equipotent fentanyl.

To evaluate the role of sufentanil and fentanyl in the prevention of cardiovascular responses to endotracheal intubation in elderly patients with coronary heart disease (CHD). Seventy-one CHD patients scheduled for surgery under general anesthesia were randomly divided into two groups to receive either 0.4 µg/kg of sufentanil (n=35) or 4 µg/kg of fentanyl (n=36) in a double-blind manner. Under local anesthesia, an invasive arterial catheter is used to monitor systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MAP). Laryngoscopy and tracheal intubation were successfully performed within 30 seconds. MAP and heart rate (HR) were recorded before anesthesia induction, immediately before intubation, at intubation, and 1, 3, 5 min after tracheal intubation. Rate pressure product (RPP) is calculated by SBP multiple HR. Patients in the fentanyl group showed a significant increase in MAP, HR, and RPP associated with tracheal intubation. However, the cardiovascular stimulation induced by tracheal intubation was attenuated in the sufentanil group. Laryngoscope and endotracheal intubation may cause adverse increases in blood pressure (BP) and HR in elderly patients with CHD, resulting in an imbalance of myocardial oxygen consumption and supply and myocardial ischemia. Anesthesia induction with sufentanil 0.4 µg/kg is more potential than fentanyl 4 µg/kg to attenuate the cardiovascular intubation response.

Damage Control Resuscitation Supplemented with Vasopressin in a Severe Polytrauma Model with Traumatic Brain Injury and Uncontrolled Internal Hemorrhage.

Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of traumatic death worldwide and particularly on the battlefield. They are especially challenging when present simultaneously (polytrauma), and clear blood pressure end points during fluid resuscitation are not well described for this situation. The goal of this study is to evaluate for any benefit of increasing blood pressure using a vasopressor on brain blood flow during initial fluid resuscitation in a swine polytrauma model. We used a swine polytrauma model with simultaneous TBI, femur fracture, and HS with uncontrolled noncompressible internal bleeding from an aortic tear injury. Five animals were assigned to each of three experimental groups (hydroxyethyl starch only [HES], HES + 0.4 U/kg vasopressin, and no fluid resuscitation [No Fluids]). Fluids were given as two 10 mL/kg boluses according to tactical field care guidelines. Primary outcomes were mean arterial blood pressure (MAP) and brain blood flow at 60 min. Secondary outcomes were blood flows in the heart, intestine, and kidney; arterial blood lactate level; and survival at 6 hr. Organ blood flow was measured using injection of colored microspheres. Five animals were tested in each of the three groups. There was a statistically significant increase in MAP with vasopressin compared with other experimental groups, but no significant increase in brain blood flow during the first 60 min of resuscitation. The vasopressin group also exhibited greater total internal hemorrhage volume and rate. There was no difference in survival at 6 hours. In this experimental swine polytrauma model, increasing blood pressure with vasopressin did not improve brain perfusion, likely due to increased internal hemorrhage. Effective hemostasis should remain the top priority for field treatment of the polytrauma casualty with TBI.

Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs

ObjectiveTo examine the accuracy of plethysmography variability index (PVI) as a noninvasive indicator of fluid responsiveness in hypovolaemic dogs. Study designProspective experimental study. AnimalsSix adult healthy sevoflurane-anaesthetized Beagle dogs. MethodsDogs were anaesthetized with 1.3-fold their individual minimum alveolar concentration of sevoflurane. The lungs were mechanically ventilated after neuromuscular blockade with vecuronium bromide. Cardiopulmonary variables including mean arterial blood pressure (MAP), central venous pressure (CVP), transpulmonary thermodilution cardiac output (TPTDCO), stroke volume (SV), perfusion index (PI), pulse pressure variation (PPV), stroke volume variation (SVV) and PVI were determined during six stages of graded venous blood withdrawal (5 mL kg−1 increments) and six stages of graded blood infusion (5 mL kg−1 increments). The cardiopulmonary variables were analysed using paired t test or Wilcoxon signed rank test. Correlations between PPV and SVV or PVI were analysed by linear regression. The accuracy of PPV, SVV and PVI for predicting fluid responsiveness was examined by using receiver operating characteristic curve analysis. A value of p < 0.05 was considered statistically significant. ResultsBlood withdrawal resulted in significant increases in PPV and PVI and decreases in MAP, CVP, TPTDCO, SV and PI. Blood infusion resulted in significant increases in MAP, CVP, TPTDCO, SV and PI and decreases in PPV and PVI. PPV and PVI showed a relevant correlation (p < 0.001, r2 = 0.62) and threshold values of PPV ≥ 16% (sensitivity 71%, specificity 82%) and PVI ≥ 12% (sensitivity 78%, specificity 72%) for identifying fluid responsiveness. SVV did not change. Conclusions and clinical relevanceNoninvasive measurement of PVI predicted fluid responsiveness with moderate accuracy equal to PPV in sevoflurane-anaesthetized mechanically ventilated dogs. Provisional threshold values for identification of fluid responsiveness were PPV ≥ 16% and PVI ≥ 12%. Clinical trials are needed to confirm these threshold values in dogs.

Centrally administered TNF increases arterial blood pressure independently of nitric oxide synthase

IntroductionEmerging evidence indicates that increased levels of TNF in the brain are associated with hypertension. Nitric oxide synthase (NOS) is involved in the central control of the cardiovascular system, exerting both pro- and antihypertensive effects. TNF induces hypothalamic synthesis of nitric oxide. AimWe checked if acutely administered TNF into the cerebral ventricles affects arterial blood pressure, heart rate and baroreflex sensitivity, and whether TNF actions are dependent on NOS in normotensive rats. MethodsWe carried out hemodynamic measurements in 6 groups of freely moving, adult Sprague-Dawley male rats, intracerebroventricularly (ICV) infused with either: 1) saline (5μl/h); 2) TNF (200ng/5μl/h); 3) non-selective NO synthase inhibitor – l-NG-Nitroarginine Methyl Ester (l-NAME) (1mg/5μl/h); 4) TNF together with l-NAME (200ng and 1mg/5μl/h, respectively); 5) neuronal NO synthase inhibitor – 7-nitroindazole sodium salt (7-NI) (20μg/10μl/h); 6) or TNF together with 7-NI (200ng and 20μg/10μl/h, respectively). Mean arterial blood pressure (MABP), heart rate (HR) and spontaneous baroreflex sensitivity (sBRS) evaluated by the sequence method were analysed. ResultsICV infusion of TNF caused a significant increase in MABP accompanied by a transient increase in HR, and a decrease in sBRS. ICV infusion of l-NAME increased MABP, but it did not change HR, nor sBRS. ICV infusion of 7-NI did not affect MABP, nor HR, nor sBRS. TNF administered together with l-NAME increased MABP with a transient increase in HR without changes of sBRS. Similarly, ICV infusion of TNF with 7-NI increased MABP without changes in HR and sBRS. ConclusionsCentrally administered TNF increases MABP and HR and blunts sBRS. The pressor effect of TNF appears to be independent of NOS activity in the brain. Inhibition of nNOS restores sBRS in TNF treated rats.

Hypotensive effect of S-adenosyl-L-methionine in hypertensive rats is reduced by autonomic ganglia and KATP channel blockers.

S-adenosyl-L-methionine (SAM) is an amino acid involved in a number of physiological processes in the nervous system. Some evidence suggests a therapeutic potential of SAM in hypertension. In this study we investigated the effect of intracerebroventricular (ICV) infusions of SAM on arterial blood pressure in rats. Mean arterial blood pressure (MABP) and heart rate (HR) were measured at baseline and during ICV infusion of either SAM or vehicle (aCSF; controls) in conscious, male normotensive Wistar Kyoto rats (WKY) and Spontaneously Hypertensive Rats (SHR). MABP and HR were not affected by the vehicle. WKY rats infused with SAM (10μM, 100μM and 1mM) showed a biphasic hemodynamic response i.e., mild hypotension and bradycardia followed by a significant increase in MABP and HR. On the contrary, SHR infused with SAM showed a dose-dependent hypotensive response. In separate series of experiments, pretreatment with hexamethonium, a ganglionic blocker as well as pretreatment with glibenclamide, a KATP channel blocker reduced the hemodynamic effects of SAM. SAM may affect the nervous control of arterial blood pressure via the autonomic nervous system and KATP channel-dependent mechanisms.

A Comparative Study of Effect of Propofol, Etomidate and Propofol Plus Etomidate Induction on Hemodynamic Response to Endotracheal Intubation: A RCT

Objective: The primary objective of this study was to compare the efficacy of 3 different anesthesia induction approach (Inj. Propofol, Inj. Etomidate and Inj. propofol plus Inj Etomidate) in maintaining hemodynamic stability during induction and following endotracheal intubation in elective surgery. Material and method: Ethical committee clearance taken, 90 patients aged 15 to 60 years of either sex and ASA physical status I or II scheduled for elective surgery under general anesthesia were taken for study. Written and informed consent was taken. The patients were randomly placed into three groups. Group I induced with Inj. Propofol (2.5 mg/kg) intravenous, Group II with Inj. Etomidate (0.3 mg/kg) intravenous and Group III with Inj. Propofol (1 mg/kg) plus Inj. Etomidate (0.2 mg/kg) intravenous. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP) and oxygen saturation (SPO2) were noted at different time interval. Results: Heart rate in all study groups decreases after induction and it was more in group I compared to group II and III (p<0.000) and after intubation HR increases in all three groups but this increase is greater in group II than other two groups. MAP among all three groups decreases after induction and it was more in group I than group II and III. Significant increase in MAP was seen at 1 min after intubation in all three groups but this increase was not sustained and returned to baseline in group II and III. Conclusion: The combination of etomidate plus propofol has better hemodynamic stability than etomidate alone at 1 min after intubation, though etomidate was equally stable at other points of time. The combination proved to be significantly better than either propofol or etomidate alone.

Effect of preoperative hypervolemic hemodilution with hydroxyethyl starch (130/0.4) on hemodynamics, blood loss and renal function after laparoscopic gastric bypass surgery

BackgroundIn a trial to overcome the adverse effects of pneumoperitoneum during laparoscopic gastric bypass surgery (GBP) on renal function this study investigated the effects of third generation HES 130/0.4 (6%) on renal function and blood loss during laparoscopic GBP.Patients and methodsThis study was carried out on 83 adult patients of both sexes scheduled for (GBP) surgery. Patients were randomly classified into Group I (42): received HES 130/0.4 10 ml/kg to a maximum volume 1000 ml, and Group II (41): received ringer acetate solution 10 ml/kg to a maximum volume 1000 ml within 30 min pre-operatively.Mean arterial blood pressure (MABP) and heart rate (HR) were measured before starting of fluid infusion, and every 15 min till the end of surgery. Blood loss was assessed intraoperatively and postoperatively.Intraoperative urine output was observed. Renal functions (blood urea, serum creatinine, and creatine clearance) were evaluated preoperatively and after 24 h postoperatively.ResultsIntraoperative and postoperative blood loss was comparable in both groups. Changes in mean arterial blood pressure (MABP), and heart rate (HR) were comparable in both groups except significant increase in MABP in group I from 30 min till 150 min intraoperatively (p values were 0.04, 0.03, 0.02, 0.04, 0.01, respectively). Creatinine clearance increased significantly at postoperative assessment time in group I, (p = 0.04). There was no significant difference between both groups regarding serum creatinine and blood urea. Intraoperative urine output significantly increased in group I, (p = 0.02).ConclusionInfusion of HES 130/0.4 has role in prevention of oliguria and provides renal protection without effect on hemostasis and intraoperative or postoperative blood loss.

Vasopressin decreases pulmonary-to-systemic vascular resistance ratio in a porcine model of severe hemorrhagic shock.

Vasopressors are gaining renewed interest as treatment adjuncts in hemorrhagic shock. The ideal vasoconstrictor will increase systemic blood pressure without increasing pulmonary vascular resistance (PVR), which hinders pulmonary perfusion and exacerbates hypoxemia. However, the selectivity of pressors for pulmonary versus systemic vasoconstriction during hemorrhage has not been characterized. The purpose of this study was to test the hypothesis that vasopressin (VP) has distinct effects on pulmonary versus systemic hemodynamics, unlike the catecholamine vasopressors norepinephrine (NE) and phenylephrine (PE). Anesthetized and ventilated pigs were assigned to resuscitation with saline only (n = 7) or saline with VP (n = 6), NE (n = 6), or PE (n = 6). Animals were hemorrhaged to a target volume of 30 mL/kg and a mean arterial pressure of 35 mmHg. One hour after the start of hemorrhage, animals were resuscitated with saline up to one shed blood volume, followed by either additional saline or a vasopressor. Hemodynamics and oxygenation were measured hourly for 4 h after the start of hemorrhage. Vasopressin increased systemic vascular resistance (SVR) while sparing the pulmonary vasculature, leading to a 45% decrease in the PVR/SVR ratio compared with treatment with PE. Conversely, NE induced pulmonary hypertension and led to an increased PVR/SVR ratio associated with decreased oxygen saturation. Phenylephrine and crystalloid had no significant effect on the PVR/SVR ratio. Sparing of pulmonary vasoconstriction occurs only with VP, not with administration of crystalloid or catecholamine pressors. The ability of VP to maintain blood oxygenation indicates that VP may prevent hypoxemia in the management of hemorrhagic shock.

Goal directed preemptive ephedrine attenuates the reperfusion syndrome during adult living donor liver transplantation

BackgroundEnd-stage liver disease is associated with marked hemodynamic disturbances that are further deteriorated during liver transplantation and is aggressively represented in the form of postreperfusion syndrome (PRS).AimThe aim was to test the hypothesis that preemptive ephedrine administration pre-reperfusion targeting a rational level of mean arterial blood pressure (MAP) of 85–100 mmHg, may reduce the incidence of PRS.Patient and methodsOne hundred recipients for adult living donor liver transplantation (ALDLT) were prospectively randomized into 2 groups; group C, control group and group E, who received ephedrine 2.5–5 mg/min starting 5 min before reperfusion till mean arterial blood pressure (MAP) reached 85–100 mmHg. Hemodynamic parameters including MAP, heart rate (HR), Transesophageal Doppler (TED) parameters including corrected flow time (FTc), systemic vascular resistance (SVR), and cardiac output (COP) were measured; just predrug administration, just before reperfusion, just after reperfusion, 5 min after reperfusion and at the end of surgery. Cold and warm ischemia times (C/WIT), duration of anhepatic phase and total duration of surgery were recorded. The incidence of PRS, the need of rescue vasoconstrictor for hemodynamic instability at time of reperfusion, need for postreperfusion vasoconstrictor infusions, over shooting of hemodynamics, postreperfusion fibrinolysis indicated by fibrinogen level and maximum lysis parameter of rotational thromboelastometry (ROTEM) were compared between both groups.ResultsThe mean dose of ephedrine required was (12.5 ± 7.5 mg). Group E had statistically significant increase in MAP, SVR, and COP; just before reperfusion, just after reperfusion and 5 min after reperfusion readings. There were no statistical significant differences between the 2 groups at the end of surgery. The incidence of PRS and the need of rescue adrenaline at the time of reperfusion, and the postreperfusion need for vasoconstrictor infusion decreased significantly in group E when compared to group C. Also postoperative mechanical ventilation decreased significantly in group E.ConclusionThe preemptive goal directed titration of ephedrine against a target MAP pre-reperfusion could decrease the incidence of PRS by 40%, attenuated the hypotensive response to reperfusion and decreased the need for postreperfusion vasoconstrictor support without over shooting of any of the monitored hemodynamic indices.

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.

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.

Effects of the crude extract of the fruit rind of rambutan (Nephelium lappaceum L.) on blood pressure, heart rate and respiratory rate in anaesthetized male rats

The bark of rambutan (Nephelium lappaceum L.), which is normally discarded was found to contain extremely high antioxidant activity [1]. Since polyphenols found in plants are widely known to affect the cardiovascular system, there is no evidence suggesting how polyphenols found in the crude extract of the fruit rind of rambutan did. We, therefore, investigated acute effects of rambutan on cardiovascular and respiratory responses in male rats. The ethanolic rambutan bark extract with a total phenolic content of 18.69±0.2mg gallic acid/g dry sample extract were used in this experiment. Invasive arterial blood pressure, heart rate and respiratory rate were recorded in pentobarbital-anaesthetized male rats for 2 hours after single i.p. injected with vehicle (n=8) and 1g/kg rambutan bark extract (n=8). Intragroup comparison showed that rambutan rind extract markedly increased mean arterial blood pressure (MABP) and systolic blood pressure (p<0.05, compared to baseline). In comparison between groups, significant increases in MABP, systolic blood pressure, diastolic blood pressure and heart rate can be observed 60 minutes after rambutan bark extract (p<0.05, two way repeated measures ANOVA). Significant increases in those parameters were found over the rest period of investigation. However, there were no changes in respiratory rate In conclusion, this study provided the first evidence of prolonged cardiovascular response (increases in MABP, systolic blood pressure and heart rate) following acute rambutan rind extract in anesthetized male rats. The mechanism of which rambutan rind extract regulating blood pressure in normotensive, hypotensive and hypertensive conditions should be further investigated.

Simvastatin Reduces Pressor Response to Centrally Administered Angiotensin II

Angiotensin II (Ang II) plays a pivotal role in regulation of the circulatory system. Activation of angiotensin type 1 (AT1) receptors in several brain regions leads to an increase in blood pressure. Accumulating data suggest that statins affect the peripheral action of Ang II; however, their central effects are poorly recognized. The study was aimed to determine whether simvastatin interferes with the brain angiotensin system in rats. Twelve-week-old, Sprague-Dawley rats were divided into two groups. Untreated group was maintained on tap water, whereas simvastatin group received water containing simvastatin for the following 12 weeks. Later, both groups were subjected to experiments in which mean arterial blood pressure (MABP) and heart rate (HR) were recorded during baseline conditions and after intracerebroventricular (ICV) infusion of either saline, Ang II, or losartan. ICV infusion of Ang II elicited a significant increase in MABP in both groups. However, the pressor response in the simvastatin group was significantly smaller than that in the untreated group. There was no significant change in MABP after ICV infusion of saline or losartan. ICV infusion of Ang II elicited a significant increase in HR in the untreated group but not in the simvastatin group. There was no significant change in HR after ICV infusion of saline or losartan. The results show that simvastatin reduces the pressor response to ICV-infused Ang II in rats. This implies that statins may affect the central regulation of the circulatory system, especially when the brain angiotensin system is stimulated.

Impairment of cerebral hemodynamic response to the cold pressor test in patients with Parkinson's disease

Background and purpose Disturbance of the autonomic nervous system (ANS) is frequently encountered in Parkinson's disease (PD). In this study, we examined changes in systemic and cerebral hemodynamics during the cold pressor test (CPT) to determine whether cerebrovascular reactivity, controlled by the sympathetic nervous system, is intact or impaired in patients with PD. Methods Forty-nine patients with PD and 49 sex- and age-matched non-PD subjects were evaluated. Measurements were performed in the resting state and over a period of 1 min of CPT. The cerebral blood flow velocity (CBFV) and pulsatility index (PI) of the middle cerebral artery (MCA) were recorded by transcranial color-coded Doppler ultrasonography (TCCS). Mean arterial blood pressure (MAP), heart rate (HR), and end-tidal CO 2 (Et-CO 2) were investigated simultaneously. The resistance of the cerebrovascular bed (CVR) was calculated as the ratio of mean arterial blood pressure to mean cerebral blood flow velocity (V m). Changes of V m, PI and CVR in response to the cold pressor test were evaluated. Results Baseline values for control and PD subjects showed no statistical difference. CPT induced a significant increase in MAP, HR, and V m in both groups. Pulsatility index (PI) and CVR were decreased in both groups during CPT. Percent increases of V m ( P < 0.001) and MAP ( P = 0.011) were significantly higher while the percent decreases of PI ( P = 0.002) and CVR ( P = 0.007) were significantly decreased more in the non-PD group. Conclusions This study indirectly shows that ANS-mediated cerebrovascular reactivity is impaired in patients with PD. Further investigations are needed to confirm the hypothesis that using the cold pressor test to evaluate cerebrovascular reactivity might be beneficial in early diagnosis of impairment of ANS-mediated cerebrovascular autoregulation in patients with PD.

Renal denervation eliminates the natriuretic effect of isotensive sodium loading in conscious rats

It was hypothesized that the renal nerve activity (RNA) mediates the natriuretic response to an infusion of NaCl, which does not change mean arterial blood pressure (MABP). This was tested in trained rats supplied with appropriate chronic instrumentation. NaCl solution (1 M) was infused i.v. at 0.02 ml/min/kg (4–5 μl/min) for 2 h during measurements of circulatory, endocrine, and renal variables including RNA. During NaCl infusion RNA decreased by 15% (p&lt;0.05) within 30 min of infusion and reached a nadir of −25% (p&lt;0.05). Renal denervation per se decreased MABP by 15.5 mmHg (p&lt;0.01). In sham operated rats, NaCl infusion increased plasma Na+ by 1.6 mmol/l (repeated measures ANOVA, p&lt;0.03) but left MABP unchanged while heart rate (HR) decreased (455±7 to 427±7 bpm, p&lt;0.0001). Urine flow tended to increase (p=0.056); sodium excretion increased 4‐fold (1.4±0.2 to 6.0±0.6 μmol/min, p&lt;0.0001) while potassium excretion remained stable (2.2±0.3 to 2.3±0.4 μmol/min). NaCl infusion to renally denervated rats decreased HR similarly (423±17 to 393±20 bpm, p&lt;0.005). In contrast, however, sodium excretion remained constant (2.2±0.8 to 3.9±0.9, p=0.68) despite a significant increase in MABP (102±3 to 109±3 mmHg, p&lt;0.0001). It is concluded that a physiological sodium load increases sodium excretion by mechanisms dependent on renal nerves.Supported by the Danish Medical Research Council and the Novo Nordisk Foundation.

Leg crossing with muscle tensing, a physical counter-manoeuvre to prevent syncope, enhances leg blood flow

In patients with orthostatic intolerance, the mechanisms to maintain BP (blood pressure) fail. A physical counter-manoeuvre to postpone or even prevent orthostatic intolerance in these patients is leg crossing combined with muscle tensing. Although the central haemodynamic effects of physical counter-manoeuvres are well documented, not much is known about the peripheral haemodynamic events. Therefore the purpose of the present study was to examine the peripheral haemodynamic effects of leg crossing combined with muscle tensing during 70 degrees head-up tilt. Healthy subjects (n=13) were monitored for 10 min in the supine position followed by 10 min in 70 degrees head-up tilt and, finally, for 2 min of leg crossing with muscle tensing in 70 degrees head-up tilt. MAP (mean arterial BP), heart rate, stroke volume, cardiac output and total peripheral resistance were measured continuously by Portapres. Leg blood flow was measured using Doppler ultrasound. Leg vascular conductance was calculated as leg blood flow/MAP. A significant increase in MAP (13 mmHg), stroke volume (27%) and cardiac output (18%), a significant decrease in heart rate (-5 beats/min) and no change in total peripheral resistance during the physical counter-manoeuvre were observed when compared with baseline 70 degrees head-up tilt. A significant increase in leg blood flow (325 ml/min) and leg vascular conductance (2.9 arbitrary units) were seen during the physical counter-manoeuvre when compared with baseline 70 degrees head-up tilt. In conclusion, the present study indicates that the physical counter-manoeuvre of leg crossing combined with muscle tensing clearly enhances leg blood flow and, at the same time, elevates MAP.

Centrally administered interleukin-1 beta sensitizes to the central pressor action of angiotensin II

The objective of the present study was to find out whether brain vasopressin (AVP) and angiotensin II (Ang II) are involved in pressor response to intracerebroventricular (ICV) infusion of interleukin-1 beta (IL-1β). The experiments were performed on conscious, 12- to 14-week-old Sprague–Dawley rats. Mean arterial blood pressure (MAP) and heart rate (HR) were recorded continuously under baseline conditions and during ICV infusion periods. In the first part of the study, the rats were ICV-infused with one of the following: 0.9% NaCl saline (5 μl/h—control), IL-1β (100 ng/h), angiotensin AT1 receptor antagonist (losartan 10 μg/h), IL-1β together with losartan, V1 receptors antagonist (V1ANT), d(CH2) 5[Tyr(Me) 2,Ala-NH 2 9]AVP, 400 ng/h) or IL-1β together with V1ANT. Saline infusion did not influence MAP, while administration of IL-1β elicited a significant but transient increase in MAP. The pressor response to IL-1β was abolished by losartan but not by V1ANT. On the other hand, combined administration of IL-1β and V1ANT resulted in increase in HR, which was absent during infusion of IL-1β alone. In the second part of the study after ICV pretreatment with IL-1β or 0.9% NaCl (control), the rats received ICV infusion of one of the following: 0.9% NaCl saline, subpressor dose of Ang II (5 ng/15 s) or subpressor dose of AVP (5 ng/15 s). Subpressor doses of Ang II and AVP did not influence MAP and HR in saline-pretreated rats. The same dose of Ang II but not AVP applied in IL-1β-pretreated rats resulted in a significant increase in MAP. The study provides evidence that IL-1β through its action in the brain increases sensitivity to central pressor action of Ang II. Additionally, we found that AVP and in particular V1 receptors do not play important role in the central pressor action of IL-1β, however, they may influence its effect on HR regulation.

L‐β,β‐Dimethylcysteine attenuates the haemodynamic responses elicited by systemic injections of peroxynitrite in anaesthetized rats

1 There is direct chemical evidence that L-beta,beta-dimethylcysteine (L-penicillamine (L-PEN)) is a scavenger of peroxynitrite. The aim of this study was to determine whether L-PEN attenuates the haemodynamic responses elicited by peroxynitrite in pentobarbital-anaesthetized rats. 2 Peroxynitrite (1-20 micromol kg(-1), i.v.) elicited dose-dependent reductions in mean arterial blood pressure (MAP) and mesenteric and hindquarter vascular resistances. 3 L-PEN (2 mmol kg(-1), i.v.) elicited relatively minor but significant increases in MAP and vascular resistances. The initial reductions in MAP and vascular resistances elicited by peroxynitrite were not diminished after administration of L-PEN whereas they were much shorter in duration. As such, the total reductions in MAP and vascular resistances were markedly reduced by L-PEN. 4 The finding that L-PEN (2 mmol kg(-1), i.v.) did not affect the hypotensive or vasodilator responses elicited of the ATP-dependent potassium-channel agonist, cromakalim (3-18 microg kg(-1), i.v.), suggests that this dose of L-PEN is not a nonselective inhibitor of vasodilation. 5 These findings suggest that L-PEN may effectively scavenge peroxynitrite in vivo and/or interfere with the mechanisms by which peroxynitrite elicits its vasodilator responses.

Veno-Constriction of the Basilic Vein with Systemic Sympathetic Activation in Humans

Cardiac function is determined to a large extent by central venous volume-dependent cardiac filling pressure. Controlling the distribution of blood volume between the central and peripheral veins is therefore a key component of cardiovascular function. Reduction in peripheral venous volume via the muscle pump or vasoconstriction-induced passive venous recoil is well documented. However, in humans little is known about sympathetic venoconstriction, especially in larger conduit veins that drain the leg or arm. PURPOSE: To determine whether systemic sympathetic nervous system activation (SNA) can induce veno-constriction in human limb conduit veins. METHODS: 10 Male subjects lay supine with arms extended at heart level. Heart rate (HR) and mean arterial blood pressure (MAP) were measured using electrocardiogram (ECG) and arterial tonometry. Echo ultrasound was used to continuously measure basilic vein diameter ∼10–15 cm above the left elbow. Venous pressure was kept constant at 40 mmHg via inflation of a pressure cuff placed proximal to the site if vessel imaging. There were four experimental interventions: Physical Stress Evoked SNA (PS; maintained, vigorous lower limb isometric contraction), Mental Stress Evoked SNA (MS; STROOP word color test) Emotional Stress Evoked SNA (ES; anger interview), and a control condition (C; counting forward by one). Venous diameter was measured over 4 repeats of 2 minute baseline, 2 minute intervention, 4 minute recovery periods. The order of interventions was counter balanced. RESULTS: All data are mean VSE. All three SNA interventions resulted in significant reductions in venous diameter (mm) (baseline vs. intervention): PS – 5.91 ± 0.15 vs. 4.66 ± 0.26, P<0.05; MS – 5.85 ± 0.15 vs. 4.88 ± 0.16, P<0.05; ES – 5.90 ± 0.10 vs. 4.66 ± 0.32, P<0.05. No change was observed in the control intervention C – 5.91 ± 0.11 vs. 5.80 ± 0.12, P=NS. All three SNA interventions evoked significant increases in MAP (mmHg) (baseline vs. intervention): PS – 80.72 ± 1.81 vs. 112.50 ± 1.84, P<0.05; MS- 82.52 ± 1.86 vs. 96.12 ± 3.37, P<0.05; ES – 81.00 ± 2.49 vs. 91.71 ± 5.19, P<0.05. No change was observed in the control intervention C – 80.19 ± 2.39 vs. 83.11 ±2.90, P<0.05). CONCLUSION: Activation of systemic sympathetic nervous activity resulting in the elevation of arterial blood pressure is accompanied by constriction of the basilic conduit vein in humans. This confirms sympathetic innervation of this vein in humans and the capacity for human conduit vein volume to be regulated via sympathetic activation. Supported by: Natural Sciences and Engineering Research Council of Canada, Canada Foundation for Innovation, Ontario Innovation Trust