Neural reflex regulation of arterial pressure in pathophysiological conditions: interplay among the baroreflex, the cardiopulmonary reflexes and the chemoreflex

The maintenance of arterial pressure at levels adequate to perfuse the tissues is a basic requirement for the constancy of the internal environment and survival. The objective of the present review was to provide information about the basic reflex mechanisms that are responsible for the moment-to-moment regulation of the cardiovascular system. We demonstrate that this control is largely provided by the action of arterial and non-arterial reflexes that detect and correct changes in arterial pressure (baroreflex), blood volume or chemical composition (mechano- and chemosensitive cardiopulmonary reflexes), and changes in blood-gas composition (chemoreceptor reflex). The importance of the integration of these cardiovascular reflexes is well understood and it is clear that processing mainly occurs in the nucleus tractus solitarii, although the mechanism is poorly understood. There are several indications that the interactions of baroreflex, chemoreflex and Bezold-Jarisch reflex inputs, and the central nervous system control the activity of autonomic preganglionic neurons through parallel afferent and efferent pathways to achieve cardiovascular homeostasis. It is surprising that so little appears in the literature about the integration of these neural reflexes in cardiovascular function. Thus, our purpose was to review the interplay between peripheral neural reflex mechanisms of arterial blood pressure and blood volume regulation in physiological and pathophysiological states. Special emphasis is placed on the experimental model of arterial hypertension induced by N-nitro-L-arginine methyl ester (L-NAME) in which the interplay of these three reflexes is demonstrable

High dietary calcium decreases blood pressure in normotensive rats

This study evaluates the influence of different concentrations of calcium on blood pressure of normotensive rats. Four groups of Wistar rats (A, B, C and D) had free access to modified isocaloric and isoproteic diets containing 0.2, 0.5, 2 and 4 g% calcium as calcium carbonate for a period of 30 days. Systolic and diastolic arterial blood pressures were monitored in awake rats by the indirect tail cuff method using a Physiograph equipped with transducers and preamplifiers. Body weight and length and food intake were monitored. Under the conditions of the present experiment, the systolic and diastolic arterial blood pressures of group D rats fed a diet containing 4 g% calcium were significantly (P<0.05) lower compared to rats of the other groups.

Effect of inhibition of nitric oxide synthase on blood pressure and renal sodium handling in renal denervated rats

The role of sympathetic nerve activity in the changes in arterial blood pressure and renal function caused by the chronic administration of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, was examined in sham and bilaterally renal denervated rats. Several studies have demonstrated that sympathetic nerve activity is elevated acutely after L-NAME administration. To evaluate the role of renal nerve activity in L-NAME-induced hypertension, we compared the blood pressure response in four groups (N = 10 each) of male Wistar-Hannover rats weighing 200 to 250 g: 1) sham-operated vehicle-treated, 2) sham-operated L-NAME-treated, 3) denervated vehicle-treated, and 4) denervated L-NAME-treated rats. After renal denervation or sham surgery, one control week was followed by three weeks of oral administration of L-NAME by gavage. Arterial pressure was measured weekly in conscious rats by a tail-cuff method and renal function tests were performed in individual metabolic cages 0, 7, 14 and 21 days after the beginning of L-NAME administration. L-NAME (60 mg kg-1 day-1) progressively increased arterial pressure from 108 ± 6.0 to 149 ± 12 mmHg (P<0.05) in the sham-operated group by the third week of treatment which was accompanied by a fall in creatinine clearance from 336 ± 18 to 222 ± 59 µl min-1 100 g body weight-1 (P<0.05) and a rise in fractional urinary sodium excretion from 0.2 ± 0.04 to 1.62 ± 0.35% (P<0.05) and in sodium post-proximal fractional excretion from 0.54 ± 0.09 to 4.7 ± 0.86% (P<0.05). The development of hypertension was significantly delayed and attenuated in denervated L-NAME-treated rats. This was accompanied by a striking additional increase in fractional renal sodium and potassium excretion from 0.2 ± 0.04 to 4.5 ± 1.6% and from 0.1 ± 0.015 to 1.21 ± 0.37%, respectively, and an enhanced post-proximal sodium excretion compared to the sham-operated group. These differences occurred despite an unchanged creatinine clearance and Na+ filtered load. These results suggest that bilateral renal denervation delayed and attenuated the L-NAME-induced hypertension by promoting an additional decrease in tubule sodium reabsorption in the post-proximal segments of nephrons. Much of the hypertension caused by chronic NO synthesis inhibition is thus dependent on renal nerve activity.

Serial blood pressure measurements

The objective of the present investigation was to study the effects of a 60-s interval of venous congestion between two noninvasive measurements of arterial blood pressure (ABP) on the fluctuation of ABP, assessed by the standard deviation of the differences between two readings. ABP was measured in 345 successive patients, at rest, four times each. For 269 participants, one pair of readings was obtained with a 60-s interval and the other pair without an interval. For 76 patients, the first pair was read at the same interval, and the second pair had venous congestion interposed and there was no waiting interval. There was no increased ABP oscillation, either when there was no interval between ABP readings, or when venous congestion was interposed compared to pairs of ABP measurements performed with a 60-s interval. There was no increase in ABP oscillations when successive ABP readings were taken without an interval or even with venous congestion interposed. Contrary to the present belief, there seems to be no loss of reliability when blood pressure recordings are taken immediately one after another, in the clinical setting.

Role of nitric oxide of the median preoptic nucleus (MnPO) in the alterations of salivary flow, arterial pressure and heart rate induced by injection of pilocarpine into the MnPO and intraperitoneally

We investigated the effect of L-NAME, a nitric oxide (NO) inhibitor and sodium nitroprusside (SNP), an NO-donating agent, on pilocarpine-induced alterations in salivary flow, mean arterial blood pressure (MAP) and heart rate (HR) in rats. Male Holtzman rats (250-300 g) were implanted with a stainless steel cannula directly into the median preoptic nucleus (MnPO). Pilocarpine (10, 20, 40, 80, 160 µg) injected into the MnPO induced an increase in salivary secretion (P<0.01). Pilocarpine (1, 2, 4, 8, 16 mg/kg) ip also increased salivary secretion (P<0.01). Injection of L-NAME (40 µg) into the MnPO prior to pilocarpine (10, 20, 40, 80, 160 µg) injected into the MnPO or ip (1, 2, 4, 8, 16 mg/kg) increased salivary secretion (P<0.01). SNP (30 µg) injected into the MnPO or ip prior to pilocarpine attenuated salivary secretion (P<0.01). Pilocarpine (40 µg) injection into the MnPO increased MAP and decreased HR (P<0.01). Pilocarpine (4 mg/kg body weight) ip produced a decrease in MAP and an increase in HR (P<0.01). Injection of L-NAME (40 µg) into the MnPO prior to pilocarpine potentiated the increase in MAP and reduced HR (P<0.01). SNP (30 µg) injected into the MnPO prior to pilocarpine attenuated (100%) the effect of pilocarpine on MAP, with no effect on HR. Administration of L-NAME (40 µg) into the MnPO potentiated the effect of pilocarpine injected ip. SNP (30 µg) injected into the MnPO attenuated the effect of ip pilocarpine on MAP and HR. The present study suggests that in the rat MnPO 1) NO is important for the effects of pilocarpine on salivary flow, and 2) pilocarpine interferes with blood pressure and HR (side effects of pilocarpine), that is attenuated by NO.

Effect of intraperitoneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats

The present study evaluated the acute effect of the intraperitoneal (ip) administration of a whey protein hydrolysate (WPH) on systolic arterial blood pressure (SBP) and renal sodium handling by conscious spontaneously hypertensive rats (SHR). The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 ± 9.3 mmHg vs WPH: 176.6 ± 4.9 mmHg, N = 8, P = 0.001) and 1.0 g/kg (0.15 M NaCl: 188.5 ± 9.3 mmHg vs WPH: 163.8 ± 5.9 mmHg, N = 8, P = 0.0018). Creatinine clearance decreased significantly (P = 0.0084) in the WPH-treated group (326 ± 67 µL min-1 100 g body weight-1) compared to 0.15 M NaCl-treated (890 ± 26 µL min-1 100 g body weight-1) and captopril-treated (903 ± 72 µL min-1 100 g body weight-1) rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 ± 0.019% compared to 0.126 ± 0.041 and 0.66 ± 0.015% in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033). Similarly, the fractional potassium excretion in WPH-treated rats (0.25 ± 0.05%) was significantly lower (P = 0.0063) than in control (0.91 ± 0.15%) and captopril-treated rats (1.24 ± 0.30%), respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE)-inhibiting in vitro activity (IC50 = 0.68 mg/mL). The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin II levels are needed to support this suggestion.

Effect of saline infusion for the maintenance of blood volume on pulmonary gas exchange during temporary abdominal aortic occlusion

We analyzed the effects of saline infusion for the maintenance of blood volume on pulmonary gas exchange in ischemia-reperfusion syndrome during temporary abdominal aortic occlusion in dogs. We studied 20 adult mongrel dogs weighing 12 to 23 kg divided into two groups: ischemia-reperfusion group (IRG, N = 10) and IRG submitted to saline infusion for the maintenance of mean pulmonary arterial wedge pressure between 10 and 20 mmHg (IRG-SS, N = 10). All animals were anesthetized and maintained on spontaneous ventilation. After obtaining baseline measurements, occlusion of the supraceliac aorta was performed by the inflation of a Fogarty catheter. After 60 min of ischemia, the balloon was deflated and the animals were observed for another 60 min of reperfusion. The measurements were made at 10 and 45 min of ischemia, and 5, 30, and 60 min of reperfusion. Pulmonary gas exchange was impaired in the IRG-SS group as demonstrated by the increase of the alveolar-arterial oxygen difference (21 ± 14 in IRG-SS vs 11 ± 8 in IRG after 60 min of reperfusion, P = 0.004 in IRG-SS in relation to baseline values) and the decrease of oxygen partial pressure in arterial blood (58 ± 15 in IRG-SS vs 76 ± 15 in IRG after 60 min of reperfusion, P = 0.001 in IRG-SS in relation to baseline values), which was correlated with the highest degree of pulmonary edema in morphometric analysis (0.16 ± 0.06 in IRG-SS vs 0.09 ± 0.04 in IRG, P = 0.03 between groups). There was also a smaller ventilatory compensation of metabolic acidosis after the reperfusion. We conclude that infusion of normal saline worsened the gas exchange induced by pulmonary reperfusion injury in this experimental model.

Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect

Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.

Clinical and laboratory findings related to a favorable evolution of hantavirus pulmonary syndrome

The medical records of 27 patients with hantavirus pulmonary syndrome were analyzed according to the need for invasive mechanical ventilation in relation to the following data up on hospital admission: age, gender, fever, cough, dyspnea, systolic arterial blood pressure, heart rate, levels of hemoglobin, hematocrit, leukocytes, lymphocytes, platelets, creatinine and arterial blood gases. The volume infused during the first 24 hours after admission, the use of inotropic agents, the use of corticosteroids and the patient outcomes were also evaluated. A favorable outcome was related to systolic blood pressure³ 100mmHg, heart rate lower than 100 beats per minute, creatinine below 1.6mg/dl, arterial blood pH³ 7.35, bicarbonate higher than 15mEq/dl, oxygen saturation higher than 84.1%, lower rehydration volume in the first 24 hours of hospitalization and no use of inotropic agents. Absence of clinical and laboratory signs of circulatory shock up on admission was associated with a favorable outcome of the patients.

Evaluation of efficacy, reliability, and tolerability of sibutramine in obese patients, with an echocardiographic study

This is a double-blind, placebo-controlled study of the efficacy, safety, and tolerability of sibutramine in the management of obese patients for a 6-month period. METHOD: Sixty-one obese patients (BMI >30, <40 kg/m2), aged 18-65 years were evaluated. In the first phase of the study (30 days), the patients were given a placebo. We monitored compliance with a low-calorie diet (1200 kcal/day) and to the placebo. In the next stage, the double-blind phase (6 months), we compared placebo and sibutramine (10 mg/day). The criteria for evaluating efficacy were weight loss, reduction in body mass index (BMI), and abdominal and hip circumferences. Tolerability was assessed based on reported side effects, variation in arterial blood pressure and heart rate, metabolic profile (fasting glucose, total cholesterol and its fractions, and triglycerides), laboratory tests (renal and hepatic functions), and flow Doppler echocardiogram. RESULTS: We observed a greater weight loss (7.3 kg, 8% vs 2.6 kg, 2.8%) and a reduction in body mass index (7.4% vs 2.1%) in the sibutramine group than in the placebo group. Classifying the patients into 4 subgroups according to weight loss (weight gain, loss <5%, loss of 5% to 9.9%, and loss >10%), we observed a weight loss of >5% in 40% of the patients on sibutramine compared with 12.9% in the placebo group. We also detected weight gain in 45.2% of the placebo group compared to 20% in the sibutramine group. The sibutramine group showed improvement in HDL- cholesterol values (increased by 17%) and triglyceride values (decreased by 12.8%). This group also showed an increase in systolic blood pressure (6.7%, 5 mmHg). There were no changes in echocardiograms comparing the beginning and end of follow-up, and side effects did not lead to discontinuation of treatment. DISCUSSION: Sibutramine proved to be effective for weight loss providing an 8% loss of the initial weight. Compliance to prolonged treatment was good, and side effects did not result in discontinuation of treatment. These data confirmed the good efficacy, tolerability, and safety profiles of sibutramine for treatment of obesity.

Hypertension in employees of a University General Hospital

PURPOSE: To find out the prevalence of hypertension in employees of the Hospital and relate it to social demographic variables. METHODS: Blood pressure measurement was performed with a mercury sphygmomanometer, using an appropriate cuff size for arm circumference, weight, and height in a population sample of 864 individuals out of the 9,905 employees of a University General Hospital stratified by gender, age, and job position. RESULTS: Hypertension prevalence was 26% (62% of these reported being aware of their hypertension and 38% were unaware but had systolic/diastolic blood pressures of >140 and/or >90 mm Hg at the moment of the measurement). Of those who were aware of having hypertension, 51% were found to be hypertensive at the moment of the measurement. The prevalence was found to be 17%, 23%, and 29% (P <.05) in physicians, nursing staff, and "others", respectively. The univariate analysis showed a significant odds ratio for the male gender, age >50 years, work unit being the Institute of Radiology and the Administration Building, educational level 10 years, and body mass index >30 kg/m². The multivariate logistic regression model revealed a statistically significant association of hypertension with the following variables: gender, age, skin color, family income, and body mass index. CONCLUSIONS: Hypertension prevalence was high, mainly in those who were not physicians or members of the nursing staff. High-risk groups (obese, non-white, men, low family income) should be better advised of prevention and early diagnosis of hypertension by means of special programs.

Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease

OBJETIVE: Antihypertensive therapy with thiazides decreases coronary events in elderly patients. However, the influence of diuretics on myocardial ischemia has not been fully investigated. The aim of this study was to compare the effect of chlorthalidone and diltiazem on myocardial ischemia. METHODS: Following a randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive patients aged 73.6±4.6 years with myocardial ischemia. All patients had angiographically documented coronary artery disease. We measured patients using 48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2-week period using placebo, patients received chlorthalidone or diltiazem for 4 weeks. RESULTS: Both treatments lowered systolic and diastolic blood pressures. The number of ischemic episodes on ambulatory electrocardiogram recordings was reduced with the use of chlorthalidone (2.5±3.8) and diltiazem (3.2±4.2) when compared with placebo (7.9±8.8; p<0.05). The total duration of ischemic episodes was reduced in both treatments when compared with placebo (chlorthalidone: 19.2±31.9min; diltiazem: 19.3±29.6min; placebo: 46.1±55.3min; p<0.05). CONCLUSION: In elderly hypertensive patients with coronary artery disease, chlorthalidone reduced myocardial ischemia similarly to diltiazem. This result is consistent with epidemiological studies and suggests that reduction of arterial blood pressure with thiazide therapy plays an important role in decreasing myocardial ischemia.

Exercise stress testing in healthy subjects during cholinergic stimulation after a single dose of pyridostigmine

OBJETIVE: The evaluation, by exercise stress testing, of the cardiorespiratory effects of pyridostigmine (PYR), a reversible acetylcholinesterase inhibitor. METHODS: A double-blind, randomized, cross-over, placebo-controlled comparison of hemodynamic and ventilation variables of 10 healthy subjects who underwent three exercise stress tests (the first for adaptation and determination of tolerance to exercise, the other two after administration of placebo or 45mg of PYR). RESULTS: Heart rate at rest was: 68±3 vs 68±3bpm before and after placebo, respectively (P=0.38); 70±2 vs 59±2bpm, before and after pyridostigmine, respectively (P<0.01). During exercise, relative to placebo: a significantly lower heart rate after PYR at, respectively, 20% (P=0.02), 40% (P=0.03), 80% (P=0.05) and 100% (P=0.02) of peak effort was observed. No significant differences were observed in arterial blood pressure, oxygen consumption at submaximal and maximal effort, exercise duration, respiratory ratio, CO2 production, ventilation threshold, minute ventilation, and oxygen pulse. CONCLUSION: Pyridostigmine, at a dose of 45mg, decreases heart rate at rest and during exercise, with minimal side effects and without interfering with exercise tolerance and ventilation variables.

Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area

OBJECTIVE: We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar¹, Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3% NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. METHODS: Holtzman rats were used . Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-mul volumes for 10-15 seconds. Seven days after brain surgery, water and 3% NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. RESULTS: Losartan (40 nmol) and [Sar¹, Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar¹, Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. CONCLUSION: MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested.

Glutathion no sangue humano normal

1.) - Woodward-Fry's and Okuda-Hess technics were employed in the determination of blood glutathione in normal healthy adults of both sexes. 2.) - It was found more accurately results with the technic of Woodward and Fry than of any others for the dosage of G. S. H. of blood. 3.) - When the process of Okuda-Hess is modified by the use of an intern indicator (starch) the readings of the end-point are much more easy and therefore the results more exacts. 4.) - The averages of the data obtained for normal blood by the technic of Woodward and Fry were for men per hundred cubic cent. 27 mgrs (G.S.H); 6.6 mgrs. (G.S.S) and 33.6 mges. (G. T) and for women: 28.4 mgrs. (G.S.H), 7.8 mgrs. (G.S.S) and 36,2 mgrs. (G.T). 5.) - Autoxidation in the blood filtrate is only apreciated after 24 hs. In the first eight hours autoxidation is never observed. 6.) - The increase of glutathione in hyperglobulia is a function of the amount of red corpuscles. In acrocyanosis arterial blood is richest in these component than venous blood and this fact is in accordance with the observation of Blanchetière, Mélon and Binet for the experimental asphyxia of dogs.