beta-Endorphin modulation of pressor response to hyperventilation in hypertensive patients

After hyperventilation, systolic and diastolic blood pressure (BP) significantly decreased in 14 hypertensive patients (group 1), did not change in 9 (group 2) and increased in 8 (group 3). Basal BP, norepinephrine and dynorphin B levels were higher in group 1 than in groups 2 and 3. The decrease in BP after hyperventilation was associated with a decrease in plasma norepinephrine, Met-enkephalin and dynorphin B and an increase in beta-endorphin. Naloxone abolished the hyperventilation-induced BP and norepinephrine decreases. Our findings indicate that hyperventilation may select hypertensive patients with different sympatho-adrenergic activity and that the increase in beta-endorphin reduces BP response to hyperventilation in patients with high sympatho-adrenergic tone.     

Effect of long-term prazosin treatment on certain humoral and metabolic factors in patients with primary hypertension]

An effect of the long-term prazosin therapy on sympathetic activity, renin plasma activity and beta-endorphin and lipid blood levels was investigated in 23 patients with the primary arterial blood hypertension. Group A included 18 patients treated with prazosin, and group B - 5 patients treated with prazosin combined with propranolol. Mean daily dose of prazosin in group A was 3.0-10.0 +/- 1.3 mg in different phases of therapy whereas in group B mean daily dose of prazosin was 3.0-6.5 +/- 1.8 mg and propranolol 50-80 mg. Significant decrease in diastolic and systolic blood pressure (p < 0.01) was achieved in both groups. Additionally significant decrease in pulse rate (p < 0.01) was seen in group B. It was found that prazosin produced significant increase in plasma noradrenaline in group A and decrease in 4-hydroxy-3-methoxyglycol excretion with the urine (p < 0.05) in both groups. Moreover, negative correlation between a decrease in blood pressure (diastolic) and noradrenaline excretion with the urine (p < 0.05) was noted in group A. No effect of prazosin therapy on plasma renin activity, beta-endorphin and lipids blood levels was observed in both groups. These results suggest that prazosin therapy in patients with the primary blood hypertension exerts an effect on sympathetic activity and does not change plasma renin activity or blood beta-endorphin and lipids levels.     

Blood pressure responses to hypnotic and nonhypnotic suggestions in normotensive subjects

Forty normotensive subjects participated on a voluntary basis in a study designed to compare the effect of suggestions on blood pressure (BP). Two experimental groups received suggestions presumed to be specific in lowering or raising BP after simple relaxation (relaxation group) or hypnotic induction (hypnotic group). A control group was used to record the BP changes over time. The time variable was significant for both systolic (SBP) and diastolic blood pressure (DBP). Induction procedures (hypnosis or relaxation) resulted in significant decreases in DBP in both experimental groups. In the control group there was a significant decrease in SBP. A specific suggestion to increase the BP resulted only in DBP increase in the hypnotic group. This group also gave an increase of both SBP and DBP over the entire experiment, whereas the relaxation group resulted in a significant decrease in SBP. There was no significant group variable, indicating no differences between the groups. Further research is needed to enable firm conclusions of the effect of suggestions on BP.     

Effect of respiratory alkalosis during exercise on blood lactate

A biofeedback model of hyperventilation during exercise was used to assess the independent effects of pH, arterial CO2 partial pressure (PaCO2), and minute ventilation on blood lactate during exercise. Eight normal subjects were studied with progressive upright bicycle exercise (2-min intervals, 25-W increments) under three experimental conditions in random order. Arterialized venous blood was drawn at each work load for measurement of blood lactate, pH, and PaCO2. Results were compared with those from reproducible control tests. Experimental conditions were 1) biofeedback hyperventilation (to increase pH by 0.08-0.10 at each work load); 2) hyperventilation following acetazolamide (which returned pH to control values despite ventilation and PaCO2 identical to condition 1); and 3) metabolic acidosis induced by acetazolamide (with spontaneous ventilation). The results showed an increase in blood lactate during hyperventilation. Blood lactate was similar to control with hyperventilation after acetazolamide, suggesting that the change was due to pH and not to PaCO2 or total ventilation. Exercise during metabolic acidosis (acetazolamide alone) was associated with blood lactate lower than control values. Respiratory alkalosis during exercise increases blood lactate. This is due to the increase in pH and not to the increase in ventilation or the decrease in PaCO2.     

Hyperventilation alters arterial baroreflex control of heart rate and muscle sympathetic nerve activity

Interactions between mechanisms governing ventilation and blood pressure (BP) are not well understood. We studied in 11 resting normal subjects the effects of sustained isocapnic hyperventilation on arterial baroreceptor sensitivity, determined as the alpha index between oscillations in systolic BP (SBP) generated by respiration and oscillations present in R-R intervals (RR) and in peripheral sympathetic nerve traffic [muscle sympathetic nerve activity (MSNA)]. Tidal volume increased from 478 +/- 24 to 1,499 +/- 84 ml and raised SBP from 118 +/- 2 to 125 +/- 3 mmHg, whereas RR decreased from 947 +/- 18 to 855 +/- 11 ms (all P < 0.0001); MSNA did not change. Hyperventilation reduced arterial baroreflex sensitivity to oscillations in SBP at both cardiac (from 13 +/- 1 to 9 +/- 1 ms/mmHg, P < 0.001) and MSNA levels (by -37 +/- 5%, P < 0.0001). Thus increased BP during hyperventilation does not elicit any reduction in either heart rate or MSNA. Baroreflex modulation of RR and MSNA in response to hyperventilation-induced BP oscillations is attenuated. Blunted baroreflex gain during hyperventilation may be a mechanism that facilitates simultaneous increases in BP, heart rate, and sympathetic activity during dynamic exercise and chemoreceptor activation.     

Role of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) in the regulation of blood pressure by leptin in lean and obese rats

We investigated the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in hemodynamic action of leptin. The effect of leptin (1 mg/kg i.p.) on systolic blood pressure (SBP) was examined in lean rats and in rats made obese by feeding highly palatable diet for either 1 or 3 months. Separate groups received NO synthase inhibitor, L-NAME, or EDHF inhibitors, the mixture of apamin+charybdotoxin or sulfaphenazole, before leptin administration. Leptin increased NO production, as evidenced by increase in plasma and urinary NO metabolites and cyclic GMP. This effect was impaired in both obese groups. In lean rats either leptin or EDHF inhibitors had no effect on blood pressure. L-NAME increased blood pressure in lean animals and this effect was prevented by leptin. However, when leptin was administered to animals pretreated with both L-NAME and EDHF inhibitors, blood pressure increased even more than after L-NAME alone. In the 1-month obese group leptin had no effect on SBP, however, pressor effect of leptin was observed in animals pretreated with EDHF inhibitors. In the 3-month obese group leptin alone increased SBP, and EDHF inhibitors did not augment its pressor effect. The results suggest that leptin may stimulate EDHF when NO becomes deficient, e.g. after NOS blockade or in short-term obesity. Although the effect of leptin on NO production is impaired in the 1-month obese group, BP does not increase, probably because EDHF compensates for NO deficiency. In contrast, leptin increases BP in 3-month obesity because its effect on EDHF is also attenuated.     

Adrenergic and dopaminergic regulation of circulating beta-endorphin-like immunoreactivity in hypertension.

The central alpha-2-adrenergic receptor agonist, clonidine (300 micrograms daily) significantly increased the plasma beta-endorphin-like immunoreactivity (beta ELI) in 12 patients with mild to moderate essential hypertension in a randomized, crossover study. A significant linear correlation between the increase in plasma beta ELI and the decrease in blood pressure (both systolic and diastolic) was found after clonidine administration. The role of the reduced central sympathetic tone, induced by alpha-2-adrenoceptor stimulation, in the elevation of circulating beta ELI can be suggested. The plasma beta ELI increased also significantly after the dopaminergic D-2 receptor agonist, bromocryptine treatment, (5 mg, daily) in 13 patients with borderline and mild essential hypertension in a randomized, crossover study. A significant drop in circulating noradrenaline and in arterial blood pressure and a significant linear correlation between the changes of plasma noradrenaline level and blood pressure was found after bromocryptine administration. There was no correlation between the rise in plasma beta ELI and the decrease in blood pressure after bromocryptine. The importance of the central sympathetic activity and not only a direct pituitary dopaminergic agonist effect on the beta-endorphin secretion can be stressed in the effect of bromocryptine on the immunoreactive beta-endorphin level.     

Effects of dynorphin A(1-13) and of fragments of beta-endorphin on blood pressure and heart rate of anesthetized rats.

The effect on blood pressure and heart rate of central administration of dynorphin A(1-13) and of beta-, gamma-, and alpha-endorphin related peptides was studied in urethane-anesthetized rats. Intracerebroventricular (i.c.v., 0.1-10 micrograms) administration of beta-endorphin resulted in a dose-dependent, naltrexone-reversible hypotension and bradycardia. N-terminally modified fragments of beta-endorphin did not reduce blood pressure and heart rate. On the other hand, a dose of 10 micrograms of beta-endorphin(1-27), which lacks the four C-terminal amino acid residues of beta-endorphin, induced a fall in blood pressure and had a biphasic effect on heart rate. These responses, however, were resistant to pretreatment with naltrexone. None of the fragments of beta-endorphin smaller than beta-endorphin(1-27) affected blood pressure when administered i.c.v. in a dose of 10 micrograms. A small transient bradycardia was observed after i.c.v. administration of 10 micrograms of beta-endorphin(1-26), alpha, and gamma-endorphin. The naltrexone-reversible bradycardic response of alpha- and gamma-endorphin was not present in des-tyrosine- and des-enkephalin-alpha- and gamma-endorphin and also not in alpha-endorphin(10-16) and gamma-endorphin(10-17). Upon i.c.v. administration (0.1-50 micrograms) a dose-dependent, naltrexone-reversible decrease in blood pressure and heart rate was induced by dynorphin A(1-13). The present data indicate a hypotensive influence of beta-endorphin, beta-endorphin(1-27), and dynorphin A(1-13), whereas other fragments of beta-endorphin had little or no effect on the cardiovascular parameters investigated.     

Contribution of captopril thiol group to the prevention of spontaneous hypertension

We aimed to compare the effect of angiotensin converting enzyme (ACE) inhibitors captopril (containing thiol group) and enalapril (without thiol group) on the development of spontaneous hypertension and to analyze mechanisms of their actions, particularly effects on oxidative stress and NO production. Six-week-old SHR were divided into three groups: control, group receiving captopril (50 mg/kg/day) or enalapril (50 mg/kg/day) for 6 weeks. At the end of experiment, systolic blood pressure (SBP) increased by 41 % in controls. Both captopril and enalapril prevented blood pressure increase, however, SBP in the captopril group (121+/-5 mmHg) was significantly lower than that in the enalapril group (140+/-5 mmHg). Concentration of conjugated dienes in the aorta was significantly lower in the captopril group compared to the enalapril group. Captopril and enalapril increased NO synthase activity in the heart and aorta to the similar level. Neither captopril nor enalapril was, however, able to increase the expression of eNOS. Both ACE inhibitors increased the level of cGMP. However, cGMP level was significantly higher in the aorta of captopril group. We conclude that captopril, beside inhibition of ACE, prevented hypertension by increasing NO synthase activity and by simultaneous decrease of oxidative stress which resulted in increase of cGMP concentration.     

老年肥胖型正常高值血压患者24h-动态血压变异特点及与动脉僵硬度的相关性研究

摘要 目的：探讨老年肥胖型正常高值血压患者24h-动态血压变异特点及与动脉僵硬度的相关性。方法：选择2018年1月~2020年5月期间在我院住院的老年正常高值血压患者174例作为研究对象,根据腰围分为腹型肥胖组（n=85）和非腹型肥胖组（n=89）。所有受试者监测24h-动态血压[包括24h平均收缩压（24h-SBP）、白昼平均舒张压（dDBP）、24h平均舒张压（24h-DBP）、夜间平均收缩压（nSBP）、白昼平均收缩压（dSBP）、夜间平均收缩压（nDBP）、血压变异系数（CV）]和颈-桡动脉脉搏传导速度（crPWV）,分析24h-动态血压变异性、节律性特点和crPWV的影响因素。结果：腹型肥胖组患者非杓型血压、24h-SBP-CV、24h-DBP-CV、dSBP-CV、nSBP-CV、夜间SBP下降率以及crPWV均高于非腹型肥胖组（P<0.05）,腹型肥胖组患者动脉僵硬度增高发生率高于非腹型肥胖组患者（P<0.05）。控制混杂因素后,腹型肥胖组患者腰围与夜间SBP下降率（r=0.338）、24h-SBP-CV（r=0.279）、24h-DBP-CV（r=0.259）、dSBP-CV（r=0.208）、nSBP-CV（r=0.317）、crPWV（r=0.543）呈正相关性（P<0.05）。经多元线性回归分析结果显示,腰围、LDL-C、夜间SBP下降率、24h-SBP-CV和nSBP-CV是crPWV的重要影响因素（P<0.05）。结论：腹部脂肪沉积对老年正常高值血压患者24h动态血压变异性和动脉僵硬度有显著影响,部分24h-动态血压参数与动脉僵硬度有关,控制腰围对预防动脉硬化有着重要的意义。     

Interrelations of hypocapnia, hypoxia, cerebral blood flow and electrical activity of the brain under voluntary hyperventilation in humans

Changes of different physiological parameters in human caused by hyperventilation of 3-min and longer duration were investigated and correlated. It was found that during 3-min hyperventilation, resulting in 4.5-5 fold increase of the respiration velocity, similar phasing changes of the central and cerebral haemodynamics occurred. The blood flow velocity according to the rheographic data during the hyperventilation first increases, reaching maximum at 1st - 2nd min of the test, and then decreases, reaching minimum at 2nd - 3rd min after it's end, and then slowly increases. Cerebral blood flow velocity during all the 3 min of the hyperventilation in most of the subjects keeps being increased, and after the test - decreased. At the same time transcutaneous pressure of carbon dioxide changes differently - decreases to minimum (approximately 25 mmHg) at the end of the test and then increases, reaching approximately 90% of the background level, at 5th min after the end of the test. Oxygen saturation of the blood during the test is found to be 98-100% and decreases to 90% at 5th min after it's end, which in overall with cerebral blood flow decrease appears to be the factor of the brain's hypoxia. In different subjects "mirror" changes of the EEG spectral power of different EEG ranges in relation to transcutaneous pressure of carbon dioxide dynamics were revealed by the hyperventilation. Taking into account the factors of duration or recurrence of the hyperventilation is important for the understanding the interrelations of cerebral haemodynamics, hypocapnia, hypoxia and electrical activity of the brain. It was found that after the recurrent hyperventilation of increasing amount (several times in hour by 3 min) cerebral blood flow might decrease markedly against the background of relatively small changes of electrical activity of the brain. The discussing of the data presented in the paper is carried out from the point of view of important role of tissue oxygen utilization mechanisms of the brain in adaptation to hypoxia and hypocapnia.     

Effects of drugs interfering with the metabolism of octopamine on blood pressure of rats

1. p-Octopamine injected in lateral ventricle of conscious spontaneously hypertensive rats decreased systolic blood pressure (SBP). 2. Precursors of octopamine--tyrosine, tyramine and phenylethanolamine (PEA)--had the same effect. The administration of pargyline, a MAO inhibitor, which increased brain octopamine, resulted in a reduction of systolic blood pressure; and this decrease was greater after administration of octopamine precursors and PEA. 3. Similarly, drugs known to inhibit activity of phenylethanolamine N-methyl-transferase (PNMT) and to increase brain octopamine level such as SKF 64139 and DCMB decreased SBP. 4. p-Octopamine hypotension was not antagonized by piperoxan, yohimbine and prazosin, a relatively selective antagonist of post-synaptic alpha adrenoceptors. 5. These results suggest that octopamine may be involved in central blood pressure regulation, and the receptors sensitive to octopamine appeared to be distinct from those receptive to the catecholamines.     

Exercise prevents leptin-induced increase in blood pressure in Sprague–Dawley rats

Although leptin has been shown to increase blood pressure (BP), it is however unclear if this increase can be prevented by exercise. This study therefore investigated the effect of leptin treatment with concurrent exercise on blood pressure (BP), sodium output, and endothelin-1 (ET-1) levels in normotensive rats. Male Sprague–Dawley rats weighing 250–270 g were divided into four groups consisting of a control group (n?=?6), leptin-treated (n?=?8), non-leptin-treated exercise group (n?=?8), and a leptin-treated exercise group (n?=?8). Leptin was given subcutaneously daily for 14 days (60 μg/kg/day). Animals were exercised on a treadmill for 30 min at a speed of 0.5 m/s and at 5° incline four times per week. Measurement of systolic blood pressure (SBP) and collection of urine samples for estimation of sodium and creatinine was done once a week. Serum samples were collected at the end of the experiment for determination of sodium, creatinine and ET-1. At day 14, mean SBP and serum ET-1 level in the leptin-treated group was significantly higher than that in the control group whereas mean SBP and serum ET-1 level was significantly lower in the leptin-treated exercise group than those in leptin-treated and control groups. Creatinine clearance, urinary sodium excretion, and urine output were not different between the four groups. Regular treadmill exercise prevents leptin-induced increases in SBP in rats, which might in part result from increased urinary sodium excretion and preventing the leptin-induced increases in serum ET-1 concentration.     

The met-enkephalin and beta-endorphin content of the blood in the early period after acute blood loss in rats

The experiments have been performed on 164 rats and 110 mice. Met-enkephalin and beta-endorphin concentration was established to increase in the blood in the early period after acute blood loss in rats who survived after 24 hours of a follow up in the group of animals, who died during 24 hours follow up, the momentary beta-endorphin increase was noted at the 1st minute of the experiment; met-enkephalin contents in blood wasn't essentially changed. mu-Receptors' agonist DAGO injection significantly decreased rat mortality in a posthemorrhagic period. The correlation between arterial pressure values and beta-endorphin and met-enkephalin contents in the blood wasn't defined. The opioid peptides' ability to increase the organism stability to hypoxia was determined. Beta-endorphin and met-enkephalin significance in the pathogenesis of a posthemorrhagic period in acute blood loss is being discussed.     

Middle cerebral artery flow velocity and pulse pressure during dynamic exercise in humans

Exercise challenges cerebral autoregulation (CA) by a large increase in pulse pressure (PP) that may make systolic pressure exceed what is normally considered the upper range of CA. This study examined the relationship between systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) and systolic (V(s)), diastolic (V(d)). and mean (V(m)) middle cerebral artery (MCA) blood flow velocity during mild, moderate, and heavy cycling exercise. Dynamic CA and steady-state changes in MCA V in relation to changes in arterial pressure were evaluated using transfer function analysis. PP increased by 37% and 57% during moderate and heavy exercise, respectively (P < 0.05), and the pulsatility of MCA V increased markedly. Thus exercise increased MCA V(m) and V(s) (P < 0.05) but tended to decrease MCA V(d) (P = 0.06). However, the normalized low-frequency transfer function gain between MAP and MCA V(m) and between SBP and MCA V(s) remained unchanged from rest to exercise, whereas that between DBP and MCA V(d) increased from rest to heavy exercise (P < 0.05). These findings suggest that during exercise, CA is challenged by a rapid decrease rather than by a rapid increase in blood pressure. However, dynamic CA remains able to modulate blood flow around the exercise-induced increase in MCA V(m), even during high-intensity exercise.     

The effects of endothelin-1 on the cardiorespiratory physiology of the freshwater trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias).

The aim of the present study was to evaluate the effects of endothelin-l-elicited cardiovascular events on respiratory gas transfer in the freshwater rainbow trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias). In both species, endothelin-1 (666 pmol kg(-1)) caused a rapid (within 4 min) reduction (ca. 30-50 mmHg) in arterial blood partial pressure of O2. The effects of endothelin-1 on arterial blood partial pressure of CO2 were not synchronised with the changes in O2 partial pressure and the responses were markedly different in trout and dogfish. In trout, arterial CO2 partial pressure was increased transiently by approximately 1.0 mmHg but the onset of the response was delayed and occurred 12 min after endothelin-1 injection. In contrast, CO2 partial pressure remained more-or-less constant in dogfish after injection of endothelin-1 and was increased only slightly (approximately 0.1 mmHg) after 60 min. Pre-treatment of trout with bovine carbonic anhydrase (5 mg ml(-1)) eliminated the increase in CO2 partial pressure that was normally observed after endothelin-1 injection. In both species, endothelin-1 injection caused a decrease in arterial blood pH that mirrored the changes in CO2 partial pressure. Endothelin-1 injection was associated with transient (trout) or persistent (dogfish) hyperventilation as indicated by pronounced increases in breathing frequency and amplitude. In trout, arterial blood pressure remained constant or was decreased slightly and was accompanied by a transient increase in systemic resistance, and a temporary reduction in cardiac output. The decrease in cardiac output was caused solely by a reduction in cardiac frequency; cardiac stroke volume was unaffected. In dogfish, arterial blood pressure was lowered by approximately 10 mmHg at 6-10 min after endothelin-1 injection but then was rapidly restored to pre-injection levels. The decrease in arterial blood pressure reflected an increase in branchial vascular resistance (as determined using in situ perfused gill preparations) that was accompanied by simultaneous decreases in systemic resistance and cardiac output. Cardiac frequency and stroke volume were reduced by endothelin-1 injection and thus both variables contributed to the changes in cardiac output. We conclude that the net consequences of endothelin-1 on arterial blood gases result from the opposing effects of reduced gill functional surface area (caused by vasoconstriction) and an increase in blood residence time within the gill (caused by decreased cardiac output.     

Opioid peptides attenuate blood pressure increase in acute respiratory failure

Plasma opioid peptides, norepinephrine, atrial natriuretic factor (ANF) and blood pressure (BP) were assessed in 24 chronic obstructive pulmonary disease patients with acute respiratory failure. Hypoxemic-hypercapnic patients had high BP, beta-endorphin, Met-enkephalin and dynorphin B, whereas hypoxemic-normocapnic and hypoxemic-hypocapnic patients showed normal BP, high beta-endorphin, and normal Met-enkephalin and dynorphin B. Norepinephrine and ANF were high in all patients, particularly in hypoxemic-hypercapnic patients. Infusion with the opioid antagonist naloxone hydrochloride significantly increased systolic blood pressure (SBP) in hypoxemic-hypercapnic (182.0 +/- 3.2 versus 205.1 +/- 3.0 mmHg; P < 0.01), hypoxemic-normocapnic (149.3 +/- 1.8 versus 169.1 +/- 2.2 mmHg; P < 0.01) and hypoxemic-hypocapnic (147.3 +/- 1.3 versus 166.8 +/- 2.2 mmHg; P < 0.01) patients, norepinephrine in hypoxemic-hypercapnic patients (3583.2 +/- 371.8 versus 5371.3 +/- 260.0 fmol/ml; P < 0.01), and reduced ANF in hypoxemic-normocapnic (18.3 +/- 0.8 versus 11.9 +/- 1.0 fmol/ml; P < 0.05) and hypoxemic-hypocapnic (18.1 +/- 1.2 versus 12.1 +/- 2.1 fmol/ml; P < 0.05) patients. These results indicate that the endogenous opioid system attenuates SBP responses in acute respiratory failure by affecting norepinephrine or ANF release.     

Critical opening pressure and reactivity of tail vessels in conscious hypertensive rats.

The possible role of increased vascular reactivity in the mechanism of experimental hypertension was studied by measurements of the critical opening pressure (COP) of tail vessels in conscious rats. In hypertension induced by administration of desoxycorticosterone acetate (DOCA) and replacement of the drinking water by 1% NaCl solution (DOCA-NaCl hypertension), and in one-kidney Goldblatt renovascular hypertension, the raised level of blood pressure was associated with an increased COP of the tail vessels when measured both before and after ganglionic blockade. In rats treated with either DOCA alone or 1% NaCl alone there was no significant increase in systolic blood pressure (SBP) or COP relative to the corresponding controls. In all four experimental series intravenous infusion of angiotensin or norepinephrine in conscious ganglion-blocked rats produced dose-dependent increases in SBP and COP. In DOCA-NaCl hypertensive rats but not in renovascular hypertensives, nor in rats treated with DOCA alone or 1% NaCl alone, the increase in COP for a given increment in dose of angiotensin or norepinephrine was significantly greater than in the control rats. It is concluded that in DOCA-NaCl hypertension there is a true increase in the reactivity of the smooth muscle of the resistance vessels to angiotensin and norepinephrine. In renovascular hypertension this is not the case and other factors must therefore be involved in causing the increased blood pressure and COP.     

The effects of endothelin-1 on the cardiorespiratory physiology of the freshwater trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias)

The aim of the present study was to evaluate the effects of endothelin-1-elicited cardiovascular events on respiratory gas transfer in the freshwater rainbow trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias). In both species, endothelin-1 (666 pmol kg^-1) caused a rapid (within 4 min) reduction (ca. 30-50 mmHg) in arterial blood partial pressure of O₂. The effects of endothelin-1 on arterial blood partial pressure of CO₂ were not synchronised with the changes in O₂ partial pressure and the responses were markedly different in trout and dogfish. In trout, arterial CO₂ partial pressure was increased transiently by ~1.0 mmHg but the onset of the response was delayed and occurred 12 min after endothelin-1 injection. In contrast, CO₂ partial pressure remained more-or-less constant in dogfish after injection of endothelin-1 and was increased only slightly (~0.1 mmHg) after 60 min. Pre-treatment of trout with bovine carbonic anhydrase (5 mg ml^-1) eliminated the increase in CO₂ partial pressure that was normally observed after endothelin-1 injection. In both species, endothelin-1 injection caused a decrease in arterial blood pH that mirrored the changes in CO₂ partial pressure. Endothelin-1 injection was associated with transient (trout) or persistent (dogfish) hyperventilation as indicated by pronounced increases in breathing frequency and amplitude. In trout, arterial blood pressure remained constant or was decreased slightly and was accompanied by a transient increase in systemic resistance, and a temporary reduction in cardiac output. The decrease in cardiac output was caused solely by a reduction in cardiac frequency; cardiac stroke volume was unaffected. In dogfish, arterial blood pressure was lowered by ~10 mmHg at 6-10 min after endothelin-1 injection but then was rapidly restored to pre-injection levels. The decrease in arterial blood pressure reflected an increase in branchial vascular resistance (as determined using in situ perfused gill preparations) that was accompanied by simultaneous decreases in systemic resistance and cardiac output. Cardiac frequency and stroke volume were reduced by endothelin-1 injection and thus both variables contributed to the changes in cardiac output. We conclude that the net consequences of endothelin-1 on arterial blood gases result from the opposing effects of reduced gill functional surface area (caused by vasoconstriction) and an increase in blood residence time within the gill (caused by decreased cardiac output.     

The acute effect of atrioventricular pacing on sympathetic nerve activity in patients with normal and depressed left ventricular function

Although modest elevations in pacing rate improve cardiac output and induce reflex sympathoinhibition, the threshold rate above which hemodynamic perturbations induce reflex sympathoexcitation remains unknown. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressures (MAP) and sympathetic nerve activity (SNA) were measured during normal sinus rhythm (NSR) and atrioventricular (AV) sequential pacing in 25 patients. Pacing was performed at 100, 120, and 140 beats/min with an AV interval of 100 ms. Patients were divided into two groups based on normal or abnormal left ventricular ejection fraction (LVEF): group 1 (n = 11; mean LVEF, 55%) and group 2 (n = 14; mean LVEF, 31%). In group 1, relative to NSR, SBP decreased an average of 2%, 3%, and 8% at 100, 120, and 140 beats/min (P < 0.001), respectively. DBP and MAP increased 9%, 15%, and 15% (P = 0.001) and 3%, 6%, and 5% [P = not significant (NS)], respectively. In group 2, SBP reductions were even greater, with an average decrease of 4%, 8%, and 16% (P < 0.001). Whereas DBP increased 9%, 9%, and 8% at 100, 120, and 140 beats/min (P = NS), MAP increased 3% and 2% at 100 and 120 beats/min but decreased 3% at 140 beats/min (P = 0.001). SNA recordings were obtained in 11 patients (6 in group 1 and 5 in group 2). In group 1, SNA decreased during all rates, with a mean 21% reduction. In group 2, however, SNA decreased at 100 and 120 beats/min (49% and 38%) but increased 24% at 140 beats/min. Patients with depressed LVEF exhibited altered hemodynamic and sympathetic responses to rapid sequential pacing. The implications of these findings in device programming and arrhythmia rate control await future studies.