Decrease In Systemic Blood Pressure Research Articles

Regulation of pulpal microcirculation by calcitonin gene-related peptide

The purpose of this study was to investigate the function of calcitonin gene-related peptide (CGRP) in regulatory mechanism of pulpal microcirculation with the aim of elucidating neurogenic inflammation. Experiments were performed on twelve cats under general anesthesia. CGRP was administered through the femoral vein to see the systemic influence and through the external carotid artery to see the local effect. Sympathetic nerve to the dental pulp was stimulated electrically and pulpal blood flow (PBF) was measured with a laser Doppler flowmeter on the canine teeth to the drug administration. The paired variables of control and experimental data were compared by paired t-test and differences with p < 0.05 were considered statistically significant. Systemic administration of CGRP (0.3 ㎍/㎏) exerted decreases in systemic blood pressure and caused changes in PBF with an initial increase followed by decrease and a more marked second increase and decrease. Close intra-arterial (i.a.) injection of CGRP (0.03 ㎍/㎏) resulted in slight PBF increase. The effect of CGRP resulted in no significant increase in PBF in the presence of CGRP 8-37. The electrical stimulation of the sympathetic nerve alone resulted in PBF decreases. The i.a. administration of CGRP following the electrical stimulation of the sympathetic nerve compensated the decreased PBF. Therefore, CGRP effectively blocked the sympathetic nerve stimulation-induced PBF decrease. Results of the present study have provided evidences that even though the local vasodilatory function of CGRP are weak, CGRP is effectively involved in blocking the vasoconstriction caused by sympathetic nerve

Bradykinin preconditioning in coronary artery bypass grafting

Background Experimental studies have shown that activation of bradykinin B 2 receptor is one of the most important triggers of ischemic preconditioning. However, the effect of exogenous administration of bradykinin in cardiac surgery is not yet known. The present prospective randomized study was designed to investigate the effect of bradykinin pretreatment in patients undergoing elective coronary artery bypass surgery. Methods Forty-one patients with multiple-vessel coronary artery disease and stable angina, admitted for the first time for elective coronary artery bypass surgery, were randomized into control or bradykinin (BK) groups. Patients in the BK group received bradykinin infusion for 7 minutes (total dose 25 μg) before the initiation of cardiopulmonary bypass. Perioperative cardiac specific troponin I (cTnI) and creatine kinase cardiac isoenzyme (CKMB) release and hemodynamics were recorded. Results Bradykinin infusion caused acute decrease of blood pressure in most of the cases and the mean minimum mean blood pressure during bradykinin infusion was 72.7% of the original mean blood pressure (MBP) level (74.7 ± 7.9 vs 54.4 ± 12.1 mm Hg, p < 0.01). There were no differences in baseline levels of cTnI and CKMB between the groups. The postoperative cTnI levels were lower than 10 ng/mL in most patients in both groups (18 in the BK group and 15 in the control group). There was no difference in cTnI between the groups. However, patients who received bradykinin released significantly less CKMB than did the controls postoperatively (6 hours, BK, 22.1 ± 9.5 vs control, 23.6 ± 12.7 U/L; 12 hours, BK, 19.4 ± 12.4 vs control, 28.7 ± 23.8 U/L; 24 hours, BK, 21.5 ± 14.7 vs control, 35.5 ± 28.9 U/L; 48 hours, BK, 14.4 ± 7.5 vs control, 23.5 ± 13.6 U/L; analysis of variance [ANOVA] for repeated measurement, p = 0.036). Maximum CKMB was also lower in the BK group (22.4 ± 14.4 vs 37.7 ± 27.5 U/L, p = 0.044). There was no significant difference between the groups in any of the hemodynamic variables. Conclusions Exogenous bradykinin infusion showed weak cardioprotective effect in the low-risk patients undergoing coronary artery bypass surgery but the dose used in the study caused acute decrease of systemic blood pressure.

Involvement of inducible nitric oxide synthase in renal failure after mild hemorrhage

The role of iNOS in rats after mild hemorrhaging was examined in this study. A mild hemorrhage (17% of total blood) induced a decrease of systemic blood pressure and heart rate, transiently followed by gradual recovery. The hemorrhage caused expression of renal iNOS mRNA and an increase in systemic NO products at 1 h after bleeding. Serum creatinine and serum urea nitrogen (UN) increased progressively up to 5 h after bleeding. Light microscopic findings showed that some inflammatory monocytes, mainly consisting of neutrophil, often existed in the glomerular capillaries, eosinophilic changes were observed in the cytoplasm at the proximal tubules, and urinary casts existed in the uriniferous space at 5 h after bleeding. The selective iNOS inhibitor, S-methylisothiourea (MTU), suppressed hemorrhagic expression of renal iNOS mRNA and systemic NO products, suppressed the increases of serum creatinine and UN, and improved renal histological aggravations induced by hemorrhaging. We speculated that MTU caused the negative circuit to suppress the renal failure through a decrease of NO generation. These results in the present study showed that iNOS expression induced by mild hemorrhaging at the early phase did participate in the development of renal failure.

24-Hour Blood Pressure On and Off Continuous Positive Airway Pressure in Patients with Obstructive Sleep Apnoea and Hypertension. 24-Stunden Blutdruck mit und ohne kontinuierlichem positivem Atemwegsdruck bei Patienten mit obstruktiver Schlafapnoe und Bluthochdruck

Question of the study Previous investigations in hypertensive patients with obstructive sleep apnoea (OSA) have shown that treatment with continuous positive airway pressure (CPAP) results in a decrease in systemic blood pressure (BP). Short-term withdrawal of CPAP therapy is not unusual, e.g. during upper respiratory tract infection. The effect of therapy interruption on BP, however, is unknown.

L’hépatite ischémique

Ischemic hepatitis is defined as an acute reversible elevation in either the serum alanine or aspartate aminotransferase level of at least 20 times the upper normal limit, excluding known causes of acute hepatitis or hepatocellular injury (viral or toxic). Histopathologic examination reveals a centrolobular liver cell necrosis. The pathophysiology of ischemic hepatitis is poorly understood. At present, the pathophysiologic hypotheses most often proposed are an ischemic/reperfusion injury of the liver and a selective hypersensitivity of the mesenteric vasculature to the renin–angiotensin axis. In ischemic hepatitis an hepatic venous congestion and a hypoxia hepatitis should be present. An underlying cardiac disease is the factor that often leads to hepatic venous congestion. The hepatic hypoxia is the result of the decrease in systemic blood pressure leading to a reduction in hepatic blood pressure or the result of a severe arterial hypoxemia. The causes of a low cardiac output are more often cardiogenic, but hypovolemia or toxic causes are possible. More rarely, a hypoxemia, without shock, is responsible for ischemic hepatitis. The incidence of ischemic hepatitis in patients admitted to intensive care unit is unknown. The mortality rate, six months after the ischemic hepatitis is 50%. The prognosis is primarily related to cardiac function.

Effect of efonidipine and ACE inhibitors on proteinuria in human hypertension with renal impairment

Background Although several lines of recent studies fail to demonstrate the beneficial action of calcium antagonists, a novel dihydropyridine efonidipine, which possesses dilatory action of both afferent and efferent arterioles and, therefore, shares the renal microvascular action with angiotensin converting enzyme (ACE) inhibitors, is reported to exhibit renal protection in experimental animals. Methods The present study evaluated the effect of efonidipine and ACE inhibitors on blood pressure (BP) and proteinuria. Sixty-eight hypertensive patients with renal impairment (serum creatinine, >1.5 mg/dL) or chronic renal parenchymal disease were randomly assigned to efonidipine or ACE inhibitor treatment. Of the 68 patients, 23 were treated with efonidipine and 20 with ACE inhibitors; these patients were analyzed for the 48-week study. Results Both efonidipine and ACE inhibitors produced a similar degree of reductions in BP (efonidipine, from 161 ± 2/93 ± 2 to 142 ± 5/82 ± 2 mm Hg; ACE inhibitor, from 163 ± 3/95 ± 2 to 141 ± 5/83 ± 2 mm Hg), and maintained creatinine clearance for 48 weeks. Proteinuria tended to decrease in both groups, and a significant reduction was observed in proteinuric patients (>1 g/day) (efonidipine, from 2.7 ± 0.3 to 2.1 ± 0.3 g/day; ACE inhibitor, from 3.0 ± 0.4 to 2.0 ± 0.5 g/day). Of interest, efonidipine decreased proteinuria in proteinuric patients who failed to manifest decreases in systemic BP. Finally, the incidence of adverse effects, including hyperkalemia and cough, was less in the efonidipine-treated group. Conclusions Both efonidipine and ACE inhibitors preserved renal function in hypertensive patients with renal impairment. The antiproteinuric effect was apparent in patients with greater proteinuria. The beneficial action of efonidipine, along with fewer side effects, may favor the use of this agent in the treatment of hypertension with renal impairment.

Force to restore the shape of an asymmetric extracorporeal tube as the basis for non-invasive pressure measurements.

A zero-balance principle is described where intraluminal pressure is estimated from the counter force needed to restore the tube shape of an elastic extra corporeal tube. The aim was to optimise cross-sectional tube geometry for tube expansion due to pressure and to reduce the sensitivity to variation in mechanical tube characteristics using an experimental statistical and factorial design. The main application is pressure monitoring in blood and dialysate tubes during hemodialysis. Improving the monitoring of the dialysis process will reduce complications, such as sudden decreases in systemic blood pressure or occlusion at the artero-venous fistula. The factorial design indicated strong influence from the geometrical characteristics of the tube as well from the geometrical design parameters of the pressure transducer. We found a consistent relationship between the intraluminal pressure and the applied force needed to restore the tube shape. The modified cross-sectional tube geometry enhances measurement sensitivity and facilitates the desired behavior of tubes during pressure applications.

Characterization and cardiovascular actions of endothelin-1 and endothelin-3 from the American alligator.

The structures and biological activities of the isoforms of endothelin (ET) in a reptile are unknown. ET-3, whose primary structure is identical to human ET-3 except for the substitution Phe4 --> Tyr, and a peptide identical to human ET-1 were isolated from an extract of the lung of the alligator, Alligator mississipiensis. Bolus intravenous injections of alligator ET-3 (10, 30, and 100 pmol/kg) into anesthetized alligators produced dose-dependent decreases in systemic blood pressure (P(sys)) and systemic vascular resistance (R(sys)) without change in heart rate (HR), systemic blood flow (Q(sys)), pulmonary pressure (P(pul)), pulmonary vascular resistance (R(pul)), or pulmonary blood flow (Q(pul)). At a dose of 300 pmol/kg, the initial vasodilatation was followed by an increase in R(sys) and decreases in Q(sys) and P(pul). The response to intravenous human/alligator ET-1 (10, 30, 100, and 300 pmol/kg) was biphasic at all doses with initial decreases in P(sys) and R(sys) being followed by sustained increases in these parameters. In the pulmonary circulation, ET-1 produced a dose-dependent decrease in Q(pul) and an increase in R(pul) during the first phase of the response but no significant change during the second phase. There was no change in HR in response to ET-1. The vasodilatator action of arginine, but not ET-1, was attenuated by N(omega)-nitro-L-arginine methyl ester, indicating that the effect of the peptide is probably not mediated through increased synthesis of nitric oxide. The data demonstrate that the structure of the ET isoforms has been strongly conserved during the evolution of vertebrates but that cardiovascular actions differ significantly between the alligator and mammals, especially in the magnitude and duration of the hypotensive response.

Cyclic adenosine monophosphate-dependent vascular responses to purinergic agonists adenosine triphosphate and uridine triphosphate in the anesthetized mouse.

The mechanism by which purinergic agonist adenosine triphosphate (ATP) and uridine triphosphate (UTP) decrease systemic arterial pressure in the anesthetized mouse was investigated. Intravenous injections of adenosine triphosphate (ATP) and uridine triphosphate (UTP) produced dose-dependent decreases in systemic blood pressure in the mouse. The order of potency was ATP > UTP. Vasodilator responses to ATP and UTP were altered by the cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor rolipram. The vascular responses to ATP and UTP were not altered by a nitric oxide synthase inhibitor, a cyclooxygenase inhibitor, a cGMP phosphodiesterase inhibitor, or a particular P2 receptor antagonist. These data suggest that ATP and UTP cause a decrease in systemic arterial pressure in the mouse via a cAMP-dependent pathway via a novel P2 receptor linked to adenylate cyclase and that nitric oxide release, prostaglandin synthesis, cGMP, and P2X1, P2Y1, and P2Y4 receptors play little or no role in the vascular effects of these purinergic agonists in the mouse.

LABETALOL DECREASES CEREBRAL PERFUSION PRESSURE WITHOUT NEGATIVELY AFFECTING CEREBRAL BLOOD FLOW IN HYPERTENSIVE GRAVIDAS

Objective: To research the cerebral hemodynamic effects of labetalol in pregnant women with hypertension. Design: Prospective observational study. Setting: Tertiary Care Medical Center. Population: Pregnant patients with hypertension. Methods: Transcranial Doppler (TCD) ultrasound was used to measure the blood velocity in the middle cerebral arteries (MCA) of eight pregnant patients with hypertension, before and after the administration of a 200 mg oral dose of labetalol. Five patients had severe preeclampsia, and three had chronic hypertension with superimposed preeclampsia. MCA blood velocity and systemic blood pressure were measured simultaneously at the baseline, and at 60 and 180 min after labetalol. Selected cerebral hemodynamic parameters were compared with normative curves. Values outside of the 5th and 95th percentiles were regarded as abnormal. Main outcome measures: Cerebral perfusion pressure (CPP), resistance area product (RAP), and cerebral flow index (CFI). Results: Patient age, gestational age, and parity were similar to those of the normal women from whom the normative data were obtained. Women with hypertension had higher baseline CPP, MAP, and RAP than normal pregnant women, but their CFI was within the normal range. Labetalol reduced the CPP, as well as the systolic, diastolic, and mean BP significantly at 60 and 180 min without significantly affecting the heart rate, MCA velocities, RAP, or CFI. Conclusions: Labetalol effectively reduces CPP, without affecting cerebral perfusion, primarily by a decrease in systemic blood pressure. This makes it an ideal agent for blood pressure control in severely hypertensive pregnant women.

The Influence of Inhaled Nitric Oxide on Cerebral Blood Flow and Metabolism in a Child with Traumatic Brain Injury

The Influence of Inhaled Nitric Oxide on Cerebral Blood Flow and Metabolism in a Child with Traumatic Brain Injury

Effect of release‐controlled nifedipine on portal hemodynamics in cirrhotic patients

OBJECTIVE: To evaluate the therapeutic effect of release‐controlled nifedipine on portal hypertension. METHODS: Thirty‐two cirrhotic patients were enrolled to investigate, by using duplex Doppler ultrasonography, differences in portal hemodynamics before and after treatment with release‐controlled nifedipine (30 mg once per day). RESULTS: After taking nifedipine, the diameter, blood velocity and blood flow of the portal vein decreased, but only the change in velocity was statistically significant. After treatment, the congestion index increased, and the blood velocity and blood flow of the splenic vein significantly decreased. The resistance and pulsatile indices of the right hepatic and splenic arteries also decreased markedly. The total hepatic blood flow was elevated slightly and there were no significant changes in mean arterial pressure and heart rate. CONCLUSIONS: The resistance and pulsatile indices of the hepatic and splenic arteries are representative indices of portal resistance. Release‐controlled nifedipine may decrease portal pressure by the following mechanisms: (i) decrease of systemic blood pressure triggers the sympathetic reflex, leading to splanchnic artery constriction and portal blood flow reduction; (ii) dilatation of the portal vein and sinusoids leads to decrease portal resistance; and (iii) dilatation of the collateral veins. Nifedipine has no significant effect on systemic circulation in normotensive cirrhotic patients, therefore it has good prospects as a drug for clinical use in portal hypertension.

Effects of sildenafil citrate (Viagra) combined with nitrate on the heart.

Sildenafil citrate (Viagra) is indicated for the treatment of erectile dysfunction. Large and sudden decreases in systemic blood pressure were reported in a substantial number of patients taking sildenafil citrate combined with nitroglycerin. We studied the effect of sildenafil citrate on the relationship between changes in systemic blood pressure and coronary blood flow. Healthy male beagles were used to assess systemic blood pressure, pulmonary arterial pressure, and flow in the left circumflex artery (in which a critical stenosis was established) and left anterior descending coronary artery. After measurement of the hemodynamic variables, 2 mg/kg sildenafil citrate was administered via a nasogastric tube. Hemodynamic changes were monitored for 1 hour. Subsequently, the acute effect of nitrate combined with sildenafil citrate was studied by the bolus injection of 0.2 mg isosorbide dinitrate before and after sildenafil citrate. Systemic blood and pulmonary arterial pressures and circumflex flow did not change during this study; however, left anterior descending coronary arterial flow increased from 16.0+/-5.8 to 24.6+/-8.7 mL/min 1 hour after administration of sildenafil citrate. The prolongation of systemic blood pressure decrease and the circumflex flow decrement induced by isosorbide dinitrate after sildenafil citrate were significantly larger and longer than those before sildenafil citrate. Sildenafil citrate had the effect of vasodilation in a normal coronary artery; however, a combined effect with nitrate resulted in large and protracted decreases in systemic blood pressure and coronary blood flow in vessels with critical stenosis.

Mechanisms behind and treatment of sudden, unexpected circulatory collapse during central neuraxis blockade.

Judging from the number of cases reported in the literature, severe bradycardia and/or asystole in association with central neuraxis blockade fortunately seems a rare complication. However, short periods of extreme bradycardia may go unnoticed and manifest cases, especially when outcome is favourable, may go unreported, and thus the real incidence may be much higher. Although the decrease in systemic blood pressure as a result of central neuraxis blockade is caused by various mechanisms, the most important factor causing severe hypotension, bradycardia and circulatory collapse is decreased venous return, and both prevention and treatment are aimed at preserving or restoring adequate venous return to the heart. Correction of preoperative hypovolaemia, limiting the extent of sensory blockade and positioning the patient so that gravity promotes venous return are the most significant preventive measures. Although a widespread custom, controversy exists regarding the efficacy of a preload; for certain categories of patients intravenous volume loading may be deleterious, and rather than a routine measure, the decision to administer a preload should be based on the clinical situation and the condition of the individual patient. For the treatment of mild bradycardia, anticholinergic drugs are the first choice. Hypotension may be treated by promoting venous return using gravity, by intravenous fluid infusion, by intravenous administration of sympathomimetic drugs, or by a combination of all three measures. In the event of sudden circulatory collapse, the first therapeutic measure that is usually immediately effective is elevation of the legs, thus promoting venous return.

Triiodothyronine repletion in infants during cardiopulmonary bypass for congenital heart disease

Objective: Cardiopulmonary bypass suppresses circulating thyroid hormone levels. Although acute triiodothyronine repletion has been evaluated in adult patients after cardiopulmonary bypass, triiodothyronine pharmacokinetics and effects have not previously been studied in infants undergoing operations for congenital heart disease. We hypothesized that triiodothyronine deficiency in the developing heart after bypass may adversely affect cardiac function reserve postoperatively. Methods: Infants less than 1 year old undergoing ventricular septal defect or tetralogy of Fallot repair were randomized into 2 groups. Group T (n = 7) received triiodothyronine (0.4 μg/kg) immediately before the start of cardiopulmonary bypass and again with myocardial reperfusion. Control (NT, n = 7) patients received saline solution placebo or no treatment. Results: These groups underwent similar ischemic and bypass times and received similar quantities of inotropic agents after the operation. The NT group demonstrated significant depression in circulating levels, compared with prebypass levels, for free triiodothyronine and total triiodothyronine at 1, 24, and 72 hours after bypass. Group T demonstrated similar low thyroxine values, but free and total triiodothyronine levels were maintained at prebypass levels for 24 hours and remained elevated over those of group NT (P <.05) at 72 hours. Heart rate was transiently elevated in group T compared with group NT (P <.05), and peak systolic pressure-rate product increased after 6 hours. Conclusion: These data imply that (1) triiodothyronine in the prescribed dose prevents circulating triiodothyronine deficiencies and (2) triiodothyronine repletion promotes elevation in heart rate without concomitant decrease in systemic blood pressure. Elevation of peak systolic pressure-rate product implies that triiodothyronine repletion improves myocardial oxygen consumption and may enhance cardiac function reserve after cardiopulmonary bypass in infants. (J Thorac Cardiovasc Surg 2000;120:604-8)

The Haemodynamic Effect of Internal Carotid Artery Stenosis on Cerebral Perfusion During Aortic Surgery

Objectives to determine the impact of the extracranial internal carotid stenosis on cerebral perfusion during aortoiliac surgery. Design prospective study. Material and methods of 432 consecutive patients undergoing aortoiliac reconstruction, 16/86 (18%) with >70% internal carotid artery stenosis, underwent inverted surgical timing (aortic reconstruction first and carotid endarterectomy second). Preoperative Transcranial Doppler (TCD) with and without acetazolamide was used to evaluate cerebrovascular reserve capacity (CRC). Intraoperatively, middle cerebral artery flow velocity (mean MCAv) and systemic blood pressure (SBP) were recorded. Results preoperatively, all 16 patients had good CRC (increase in mean MCAv: 66% right and 72% left). Intraoperatively, the mean MCAv (from 49±13 to 45±14 cm/s p=0.0249) and SBP decreased (from 127±25 to 113±22 mmHgp =0.0016). In patients with unilateral carotid disease, declamping had no effect on left mean MCAv despite a significant decrease of SBP (129±44 to 113±21 mmHg p=0.0211). In those with bilateral disease, declamping decreased both mean MCAv: from (48±12 to 39±10 cm/s p=0.011) and SBP (123±26 to 111±25 mmHg p=0.0479). No perioperative neurological deficit occurred. Conclusions if CRC is normal or still effective, aortoiliac reconstruction does not impair cerebral perfusion.

Effects of the antihypertensive drug nifedipine on albuminuria and renal histopathology in young spontaneously hypertensive rats with diabetes

We investigated the renal protective effect of nifedipine (2-nitrophenyl derivative BAY a 1040) in streptozotocin (STZ)-induced spontaneously hypertensive rats (SHRs, 8 weeks of age). Diabetic SHRs were treated with 40 mg/kg/day of nifedipine or efonidipine as controls for 16 weeks. Dosage of nifedipine or efonidipine was chosen after preliminary studies demonstrated that it showed moderate antihypertensive action (more than a 20% decrease in systemic blood pressure after treatment). In the diabetic SHR, the excretion of urinary albumin was increased and reached 4.41 ± 0.08 mg/day at 24 weeks. The levels of urinary albumin in the diabetic SHR after treatment with nifedipine were significantly less than those in the diabetic SHR at 24 weeks (p < 0.01). Levels of the ratio of creatinine clearance to body weight were significantly decreased in the diabetic SHR after treatment with nifedipine. In light microscopy, the ratio of glomerular tufts to Bowman's areas was significantly decreased compared with those in the diabetic SHRs (p < 0.05). These findings suggest that nifedipine inhibits the development of albuminuria and glomerular enlargement in STZ-induced diabetic SHRs. There was no significant difference in the changes in antihypertensive or antialbuminuric effects between nifedipine and efonidipine. Thus, nifedipine, as well as efonidipine, may become a useful antihypertensive drug with a renal protective effect.

The Short-Term Effect of Adding Brimonidine 0.2% to Timolol Treatment in Patients with Open-Angle Glaucoma

Brimonidine, a highly selective α₂-adrenoceptor agonist, was studied to determine its ocular hypotensive effect and side effects in patients with elevated intraocular pressure (IOP) while on continuing therapy with timolol. This was a prospective, randomized, placebo-controlled study in 15 patients with primary open-angle or pseudoexfoliation glaucoma on therapy receiving timolol 0.5% twice daily, with IOP greater than or equal to 22 mm Hg in one eye. IOP measurements, blood pressure and pulse rate were assessed on 2 days at a baseline and 1, 2, 4, 6 and 8 h later. A single drop of brimonidine 0.2% or placebo was added to treatment with timolol. The reductions in IOP at all time intervals observed with brimonidine + timolol were significantly greater than those with timolol + placebo. The maximum mean net decrease in IOP was 19.23 ± 10.60% at 4 h. Statistically significant decreases in systemic blood pressure and pulse rate without clinical symptoms were observed in the group receiving brimonidine + timolol. This study suggests that a combination of brimonidine and timolol may have potential in the treatment of glaucoma. Further clinical trials with brimonidine are indicated to assess its further role as adjunctive agent.

An Inhibitor of Angiotensin Converting Enzyme (Enalapril) Augments Endotoxin-Induced Hypotension in the Pig

Septic shock causes an extensive inflammatory reaction including increased capillary leakage and a decrease in systemic blood pressure. Human septic shock can be replicated in the endotoxaemic pig. Angiotensin converting enzyme (ACE) is involved in the degradation of bradykinin, an inflammatory mediator, and in the regulation of blood pressure. Inhibition of ACE is a common approach to reduce hypertension as well as left ventricular insufficiency. Fifteen anaesthetised pigs received a continuous 3 h endotoxin infusion. The animals were randomly given an inhibitor of ACE (enalapril) [at a dose (0.5 mg × kg−1 that did not per se reduce mean arterial blood pressure (MAP); (n=7)], or the corresponding volume of saline (n=8). Another seven pigs were randomised for treatment with enalapril (0.5 mg × kg−1 + saline (n=3). Four pigs were randomised to serve as untreated controls (saline + saline). Basic physiologic variables were registered. Endotoxaemia progressively reduced MAP. This decrease was significantly augmented by enalapril. Hypovolemia caused by increased permeability or salt/water excretion did not seem to explain this effect as neither blood haemoglobin nor plasma sodium differed between the two groups of endotoxaemic pigs. Inhibitors of ACE are known to potentiate the cardio - depressant effect of bradykinin. This may explain the reduction in MAP by enalapril during porcine endotoxaemia.

Improvement of renal dysfunction in dogs with endotoxemia 0000by a nonselective endothelin receptor antagonist

During endotoxemia, there is a marked and intractable decrease in systemic blood pressure, as well as profound vasoconstriction of the renal artery, thereby leading to septic shock and acute renal failure. The purpose of this study was to elucidate the effect of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, on the hemodynamic and renal vascular changes seen in endotoxemia. Prospective, comparative, experimental study. Laboratory at a university hospital. Thirty-two male mongrel dogs (12.1+/-0.4 kg) under pentobarbital anesthesia. Four groups of animals were studied: a) the lipopolysaccharide (LPS) group (n = 10), which received LPS (250 ng/kg/min for 2 hrs); b) the TAK-044 (a nonselective endothelinA/ endothelinB receptor antagonist) plus LPS group (n = 12), which received a bolus of TAK-044 (5 mg/kg) 0.5 hr before the start of LPS infusion; c) the TAK-044 plus vehicle group (n = 5), which received the same dose of TAK-044 0.5 hr before the start of vehicle infusion; and d) the control group (n = 5), which received only vehicle infusion. Changes in systemic and renal hemodynamics, blood gas, and renal function were measured at baseline, and at 0.5, 1, 2, 3, and 4 hrs. Infusion of LPS resulted in significant decreases in mean arterial pressure, arterial pH, Pao2, base excess, urine volume, renal blood flow, creatinine clearance, and urine osmolality. The administration of TAK-044 before LPS infusion did not affect the LPS-induced hypotension. In contrast, the receptor antagonist prevented LPS-induced metabolic acidosis and hypoxemia, and improved LPS-induced decreases in urine volume, renal blood flow, creatinine clearance, and urine osmolality, whereas TAK-044 or vehicle administered alone resulted in no significant hemodynamic or blood gas changes. Plasma endothelin-1 concentrations significantly increased after LPS infusion, with or without TAK-044. The present study suggests that endothelin-1 plays an important role in the impaired renal hemodynamics and renal function associated with endotoxemia, and that endothelin receptor antagonists may be useful as therapeutic agents for acute renal failure during endotoxemia.