The effect of prostaglandin E2 on the cardiovascular response to angiotensin II in pregnant rabbits

The rise in arterial blood pressure in response to angiotensin II was studied in the last third of pregnancy in rabbits. The response was compared with that of pregnant rabbits during infusion of prostaglandin E₂ and F_2α. Prostaglandin E₂ significantly diminished the rise in diastolic pressure in response to angiotensin II. Prostaglandin F_2α did not alter the response. Intravenous indomethacin elevated the blood pressure and caused an absolute increase in the pressor response. It did not mediate a change in the percentage rise in blood pressure in response to angiotensin II.     

Combined use of dopamine and prostaglandin A1 in patients with acute renal failure and hepatorenal syndrome

Dopamine and prostaglandin A₁ were infused intravenously in 4 patients with the hepatorenal syndrome, in 1 patient with acute tubular necrosis, and 1 patient with cortical necrosis. Large doses of prostaglandin A₁ decreased arterial blood pressure preventing increase in dosage; in contrast, high doses of dopamine elevated blood pressure. When the two drugs were administered conjointly, much larger doses of each agent could be administered without change in arterial blood pressure. Significant improvement of renal function was not observed in any of these critically ill patients during or within 24 hours after dopamine and prostaglandin A₁ administration. This study demonstrated that extremely large doses of these vasodilating agents can be safely administered conjointly.     

Changes of mean arterial pressure of the rat resulting from intracereboventricular injections of prostacyclin of 6-keto-prostaglandin F1 Alpha

Repeated intracerebroventicular injections of 1 μg prostacyclin reduce mean arterial pressure of conscious normotensive rats and reverse the elevation of blood pressure of conscious rats resulting from the intraventricular injection of angiotensin II. The reduction of blood pressure of normotensive rats by prostacyclin is enhanced by pretreatment with probenecid, an inhibitor of fatty-acid transport across biological membranes. Although probenecid does not completely inhibit the transport of fatty acids from the brain to the periphery, the greater effectiveness of prostacyclin in probenecid-treated animals suggests that centrally injected prostacyclin need not leak into the periphery to reduce blood pressure. When the dose of prostacyclin is reduced to 100 ng repeated each minute for 10 min, no change of blood pressure of normotensive rats is observed. The failure of the lower dose of prostacyclin to reduce blood pressure may be due to its rapid degradation. Ventricular injections of 6-keto-prostaglandin F_1a, a major product of prostacyclin metaolism, causes an increase of blood pressure which may counteract the action of prostacyclin itself.     

Effects of intra-coronary administration of leukotriene D4 in the anaesthetized dog

The left anterior descending coronary artery in anaesthetized greyhounds was perfused at constant pressure with blood pumped from the carotid artery. Phasic and mean coronary flow, left ventricular pressure, dP/dt, cardiac output, ECG, heart rate and systemic pressure were measured. Leukotriene (LT) D₄ was administered into the left anterior descending coronary artery as a bolus injection. LTD₄ caused dose-related reductions in coronary flow. Other parameters showed little immediate change although a gradual decrease in left ventricular pressure, dP/dt, cardiac output and systemic pressure occurred after administration of LTD₄. Following intracoronary administration of LTD₄ small surface haemorrhages were observed over the area perfused. The reduction in coronary flow was not inhibited by indomethacin.     

Decreased smooth muscle side effects with 16, 16-dimethyl-trans-Δ2-PGE1 methyl ester in Japanese monkey (Macaca fuscata fuscata)

The smooth muscle stimulating activity of a new PGE₁ analog, 16, 16-dimethyl-trans-Δ²-PGE₁ methyl ester (ONO-802) was evaluated by simulataneous;y recording the EMG of the uterus and intestines, along with urinary bladder pressure, and blood pressure in pregnant and non-pregnant Japanese monkeys ($\text{Macaca fuscata fuscata}$). Single intravenous injections of ONO-802 in increasing dosages (0.2–5 μg/kg) were found to be 50–100 times or more effective in inducing uterine contraction than PGF₂α and PGE₁. A mild, transient gastrointestinal muscle stimulating activity was observed, but change in urinary bladder pressure and blood pressure was not evident. ONO-802 induced uterine contractions in the pregnant animals were 10 times greater than in the non-pregnant animals. These results suggest that ONO-802 may be a suitable clinical prostaglandin for use in therapeutic abortion.     

Effect of PGD2, PGE2, PGF2α and PGI2 on blood pressure,heart rate and plasma catecholamine responses to spinal cord stimulation in the rat

The following experiments were designed in order to examine the inter-relationships of various prostaglandins (PG's) and the adrenergic nervous system, in conjunction with blood pressure and heart rate responses, $\text{in vivo}$. Stimulation of the entire spinal cord (50v, 0.3–3 Hz, 1.0 msec) of the pithed rat increased blood pressure, heart rate and plasma epinephrine (EPI) and norepinephrine (NE) concentration (radioenzymatic-thin layer chromatographic assay). Infusion of PGE₂(10–30 μg/kg. min, i.v.) suppressed blood pressure and heart rate responses to spinal cord stimulation while plasma EPI (but not NE) was augmented over levels found in control animals. PGI₂ (0.03–3.0 μg/kg. min, i.v.) suppressed the blood pressure response to spinal cord stimulation without any effect on heart rate or the plasma catecholamine levels. PGE₂ and PGF_2α(10–30 μg/kg. min, i.v.) did not change the blood pressure, heart rate or plasma EPI and NE responses to the spinal cord stimulation although PGF_2α disclosed an overall vasopressor effect during the pre-stimulation period. At the pre-stimulation period it was also observed that PGE₂, PGF_2α and PGI₂, had a positive chronotropic effect on the heart rate, the cardiac accelerating effect of PGE₂ was not abolished by propanolol. These $\text{in vivo}$ studies suggest that in the rat, PGE₂ and PGI₂ modulate sympathetic responses, primarily by interaction with the post-synaptic elements — PGE₂ on both blood vessels and the heart and PGI₂ by acting principally on blood vessels.     

Central neurotransmitter receptors in hypertensive rats

Muscarinic cholinergic ([³H]QNB), α₁ ? ([³H]WB-4101), and α₂ ? ([³H]clonidine) adrenergic ligand binding was measured in various regions of the brains of adult normotensive, spontaneously hypertensive, and DOCA-salt hypertensive rats. There was a 66% increase in the number of α₁-adrenergic receptors in hypothalamus of the spontaneously hypertensive rats as compared to normotensive controls, with no change in the K_d value. There were no other differences in the spontaneously hypertensive rats and none in the DOCA-salt model. α₁-Adrenergic binding was elevated in hypothalamus of spontaneously hypertensive rats 4–20 weeks of age even though blood pressure in the 4-week old animals was not at hypertensive levels (i.e., <150 mmHg). Treatment of adult spontaneously hypertensive rats with clonidine HCl significantly reduced blood pressure but failed to alter the binding of [³H]WB-4101 in hypothalamus. Thus, it appears that the enhanced number of α₁-adrenergic receptors in hypothalamus of spontaneously hypertensive rats is neither a consequence of the increased blood pressure, nor a phenomenon common to all models of hypertension.     

Cardiovascular responses to metabolic and respiratory acidosis and anesthesia in larval Ambystoma tigrinum

Larval Ambystoma tigrinum were examined to determine their cardiovascular responses to three types of acidosis: metabolic acidosis via NH₄Cl gavage; respiratory acidosis via hypercapnia; and anesthetic-induced acidosis, via triacine methanesulphonate. In addition, another group of (metabolic acidosis) animals were tested to determine the role of -mediated catecholamine control on cardiovascular and acid-base regulation. The metabolic and respiratory acidoses produced typical amphibian responses. Anesthesia produced a significant mixed acidosis with respiratory and metabolic components. The cardiovascular responses to metabolic and respiratory acidosis were increased heart rate and pulse pressure. There were no significant changes in diastolic pressure, however, systolic pressure increased as a result of the increased pulse pressure. Animals subjected to metabolic acidosis via -blockade with propranolol did not display the increased heart rate and pulse pressure and the acidosis was deepened and prolonged. Anesthesia resulted in a cardiac slowing and increased pulse pressure, probably explained by the Frank-Starling relationship. There was no change in diastolic pressure. Anesthetized animals had depressed blood O₂ tension and elevated blood lactate.Abbreviations HR heart rate - RBC red blood cell(s) - TMS triacine methanesulphonate     

Projections of climate‐driven changes in tuna vertical habitat based on species‐specific differences in blood oxygen affinity

Oxygen concentrations are hypothesized to decrease in many areas of the ocean as a result of anthropogenically driven climate change, resulting in habitat compression for pelagic animals. The oxygen partial pressure, pO₂, at which blood is 50% saturated (P₅₀) is a measure of blood oxygen affinity and a gauge of the tolerance of animals for low ambient oxygen. Tuna species display a wide range of blood oxygen affinities (i.e., P₅₀ values) and therefore may be differentially impacted by habitat compression as they make extensive vertical movements to forage on subdaily time scales. To project the effects of end‐of‐the‐century climate change on tuna habitat, we calculate tuna P₅₀ depths (i.e., the vertical position in the water column at which ambient pO₂ is equal to species‐specific blood P₅₀ values) from 21st century Earth System Model (ESM) projections included in the fifth phase of the Climate Model Intercomparison Project (CMIP5). Overall, we project P₅₀ depths to shoal, indicating likely habitat compression for tuna species due to climate change. Tunas that will be most impacted by shoaling are Pacific and southern bluefin tunas—habitat compression is projected for the entire geographic range of Pacific bluefin tuna and for the spawning region of southern bluefin tuna. Vertical shifts in P₅₀ depths will potentially influence resource partitioning among Pacific bluefin, bigeye, yellowfin, and skipjack tunas in the northern subtropical and eastern tropical Pacific Ocean, the Arabian Sea, and the Bay of Bengal. By establishing linkages between tuna physiology and environmental conditions, we provide a mechanistic basis to project the effects of anthropogenic climate change on tuna habitats.     

Arterial blood pressure during voluntary diving in the tufted duck,Aythya fuligula

Arterial blood pressure was monitored in voluntarily diving tufted ducks. Mean arterial blood pressure while diving increased during the pre-dive tachycardia, fell to resting levels on submersion, then gradually increased before peaking on surfacing. Estimated total peripheral resistance fell during the pre-dive and post-dive tachycardia, presumably to allow the oxygen stores to be loaded and replenished respectively and/or for carbon dioxide levels to be reduced. Changes in mean arterial blood pressure and total peripheral resistance suggest that peripheral vasoconstriction occurs in some vascular beds during a dive. An increase in arterial blood pressure (and therefore perfusion pressure) may be employed to increase blood flow and oxygen delivery to the active leg muscles.Abbreviations ecg Electrocardiogram, f _H, heart rate - MABP mean arterial blood pressure - P _b blood pressure(s) - TPR total peripheral resistance - V _b cardiac output     

Short-term adaptation of five- to seven-year-old children to mental load

Tetrapolar rheography according to Kubicek has been used to estimate the adaptive capacity of the cardiovascular system in 150 five- to seven-year-old children at rest and during mental load. Mental load evokes two variants of stroke volume (SV) responses, one of them characterized by an increase in the SV, and the other, by a decrease in the SV and an increase in the diastolic blood pressure (BP_d). Irrespective of the direction of the change in the SV, short-term adaptation to mental load in most five- to seven-year-old children does not stress the mechanisms of the cardiovascular system control and is generally favorable. In 13–15% of the children examined, short-term adaptation to mental load considerably stressed the cardiovascular system control. This is expressed in increased systolic blood pressure (BP_s), BP_d, and heart rate (HR); decreased CV and cardiac output (Q); and a prolonged restoration period for most central hemodynamic parameters.     

Influence of temperature on the optimal hematocrit of the bullfrog (Rana catesbeiana)

Summary The influence of temperature on blood viscosity and consequently on the potential for oxygen transport by blood was determined using a controlled flow, variable pressure tube viscometer, and blood from adult bullfrogs. Blood viscosity was determined as a function of hematocrit and temperature, and oxygen capacity was determined as a function of hematocrit. These data were used to describe 1) the potential for oxygen transport in the tube viscometer, and 2) the relation between the optimal hematocrit, the hematocrit which provided the greates oxygen transport, and temperature. The optimal hematocrit increased at a rate of 0.237% per °C increase in temperature. This value is close to the rate of change inin vivo hematocrit of 0.246 and 0.240% per °C increase in body temperature (T_b) observed in winter bullforgs acclimated to 5 and 20°C, respectively. During the summer the hematocrit ratio showed no consistent relation to T_b. These results suggest that in bullfrogs the cardiovascular adjustments to change in T_b involve the optimal hematocrit in winter, but not in summer.     

Effects of intracerebroventricular administration of prostaglandins I2, E2, F2α and indomethacin on blood pressure in the rat

The effects of intraventricularly administered prostaglandins I₂ (PGI2), E₂ (PGE2), F_2α (PGF2α) and indomethacin on systemic blood pressure were investigated in conscious rats. PGI2 (1.25 – 10 g/kg) decreased blood pressure in a dose-related manner, whereas PGE2 (100 – 1000 ng/kg) dose-dependently increased blood pressure. Both PGF2α (0.31 – 20 μg/kg) and indomethacin (0.625 – 40 μg/kg) had no effects on blood pressure. These results indicate that intraventricular injection of PGI2 or PGE2 can induce significant changes in blood pressure, while endogenous prostaglandins synthesized in the brain seem to play a minor role in direct regulation of systemic blood pressure in the rat.     

Use of body composition measurements to guide the assessment of dry weight in anuric dialysis patients: improvements in blood pressure control

PurposeFluid management using a body composition monitor (BCM) based on bioimpedance spectroscopy has been found to be beneficial for maintenance hemodialysis (MHD) patients. Our purpose was to provide a management procedure for the adjustment of post-dialysis overhydration (OH_post) and to evaluate whether this approach could improve blood pressure.MethodsPost-dialysis fluid status was assessed weekly using the BCM. The reference value of OH_post and the flow procedure for post-dialysis target weight (PDTW) adjustment were established via measurements of OH_post in 60 normotensive MHD patients. In the interventional study, we adjusted the PDTW of hypertensive patients to the optimal OH_post range, with a 0.2–0.5 kg change in PDTW per week.ResultsThis observational study included 130 anuric MHD patients, of whom 60 were in the pre-dialysis systolic blood pressure (sBP_pre) < 140 mmHg group. On multivariate logistic regression analysis, we found that only OH_post was significantly associated with sBP_pre ≥ 140 mmHg (odds ratio = 2.293, p = 0.000). Patients in the OH_post < ?1.8 L group were mainly male and younger, and had higher post-dialysis diastolic blood pressure, ultrafiltration volume, levels of nutrition markers (serum albumin and creatinine), body mass index, and lean tissue index (LTI). On multiple stepwise regression analysis, only the change in LTI was found to be an independent predictor of OH_post [R² 0.208, β = ?0.196, 95% CI (?0.296, ?0.095), p < 0.001]. The reference value of OH_post was found to deviate by ? 2.5–0.5 L from that of normotensive patients. At the end of the study, the systolic blood pressure of 38 patients was less than 140 mmHg after PDTW adjustment. The changes in OH_post from the initial to last adjustment were significant (t = 5.431, p < 0.001), with a substantial decrease in the sBP_pre (t = 11.208, p < 0.001).ConclusionsAssessment of OH_post and LTI using a BCM with a patient-specific optimal PDTW adjustment flow can lead to significantly better control of hypertension in anuric MHD patients.     

Effects of Slow Deep Breathing at High Altitude on Oxygen Saturation,Pulmonary and Systemic Hemodynamics

Slow deep breathing improves blood oxygenation (Sp_O2) and affects hemodynamics in hypoxic patients. We investigated the ventilatory and hemodynamic effects of slow deep breathing in normal subjects at high altitude. We collected data in healthy lowlanders staying either at 4559 m for 2–3 days (Study A; N = 39) or at 5400 m for 12–16 days (Study B; N = 28). Study variables, including Sp_O2 and systemic and pulmonary arterial pressure, were assessed before, during and after 15 minutes of breathing at 6 breaths/min. At the end of slow breathing, an increase in Sp_O2 (Study A: from 80.2±7.7% to 89.5±8.2%; Study B: from 81.0±4.2% to 88.6±4.5; both p<0.001) and significant reductions in systemic and pulmonary arterial pressure occurred. This was associated with increased tidal volume and no changes in minute ventilation or pulmonary CO diffusion. Slow deep breathing improves ventilation efficiency for oxygen as shown by blood oxygenation increase, and it reduces systemic and pulmonary blood pressure at high altitude but does not change pulmonary gas diffusion.     

Effects of prostaglandins E2, I2 and F2α, arachidonic acid and indomethacin on pressor responses to norepinephrine in conscious rats

The effects of prostaglandins E₂ (PGE₂), I₂ (PGI₂) and F₂α (PGF₂α), arachidonic acid and indomethacin on pressor responses to norepinephrine were examined in conscious rats. Intravenously infused PGE₂ (0.3, 1.25 μg/kg/min), PGI₂ (50, 100 ng/kg/min), PGF₂α (1.8, 5.4 μg/kg/min) and arachidonic acid (0.7, 1.4 mg/kg/min) did not change the basal blood pressure. Both PGE₂ and PGI₂ significantly attenuated pressor responses to norepinephrine, whereas PGF₂α significantly potentiated them. Arachidonic acid, a precursor of the prostaglandins (PGs), significantly attenuated pressor responses to norepinephrine. Since the attenuating effect of arachidonic acid was completely abolished by the pretreatment with indomethacin (5 mg/kg), arachidonic acid is thought to exert an effect through its conversion to PGs. On the contrary, intravenously injected indomethacin (0.2–5.0 mg/kg) facilitated pressor responses to norepinephrine in a dose-related manner without any direct effect on the basal blood pressure. These results suggest that endogenous PGs may participate in the regulation of blood pressure by modulating pressor responses to norepinephrine in conscious rats.     

Effect of Hemorrhagic Hypotension on Cortical Oxygen Pressure and Striatal Extracellular Dopamine in Cat Brain

This study investigated the relationships between blood pressure, cortical oxygen pressure, and extracellular striatal dopamine in the brain of adult cats during hemorrhagic hypotension and re-transfusion. Oxygen pressure in the blood of the cortex was measured by the oxygen dependent quenching of phosphorescence and extracellular dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) by in vivo microdialysis. Following a 2 h stabilization period after implantation of the microdialysis probe in the striatum, the mean arterial blood pressure (MAP) was decreased in a stepwise manner from 132 ± 2 Torr (control) to 90 Torr, 70 Torr and 50 Torr, holding the pressure at each level for 15 min. The whole blood was then retransfused and measurements were continued for 90 min. As the MAP was lowered there was a decrease in arterial pH, from a control value of 7.37 ± 0.05 to 7.26 ± 0.06. The PaCO₂ decreased during bleeding from 32.3 ± 4.8 Torr to 19.6 ± 3.6 Torr and returned to 30.9 ± 3.9 Torr after retransfusion. The PaO₂ was 125.9 ± 15 Torr during control conditions and did not significantly change during bleeding. Cortical oxygen pressure decreased with decrease in MAP, from 50 ± 2 Torr (control) to 42 ± 1 Torr, 31 ± 2 Torr and 22 ± 2 Torr, respectively. A statistically significant increase in striatal extracellular dopamine, to 2,580 ± 714% of control was observed when MAP decreased to below 70 Torr and cortical oxygen pressure decreased to below 31 Torr. When the MAP reached 50 Torr, the concentration of extracellular dopamine increased to 18,359 ± 2,764% of the control value. A statistically significant decrease in DOPAC and HVA were observed during the last step of bleeding. The data show that decreases in systemic blood pressure result in decrease in oxygen pressure in the microvasculature of the cortex, suggesting vascular dilation is not sufficient to result in a full compensation for the decreased MAP. The decrease in cortical oxygen pressure to below 32 Torr is accompanied by a marked increase in extracellular dopamine in the striatum, indicating that even such mild hypoxia can induce significant disturbance in brain metabolism.     

Circadian and Short-Term Regulation of Blood Pressure and Heart Rate in Transgenic Mice with Cardiac Overexpression of The β1-Adrenoceptor

Congestive heart failure is associated with a loss of circadian and short-term variability in blood pressure and heart rate. In order to assess the contribution of elevated cardiac sympathetic activity to the disturbed cardiovascular regulation, we monitored blood pressure and heart rate in mice with cardiac overexpression of the β₁-adrenoceptor prior to the development of overt heart failure. Telemetry transmitters for continuous monitoring of blood pressure and heart rate were implanted in 8 to 9-week-old wildtype and transgenic mice, derived from crosses of heterozygous transgenic (line β₁TG4) and wildtype mice. Cardiovascular circadian patterns were analyzed under baseline conditions and during treatment with propranolol (500 mg/L in drinking water). Short-term variability was assessed by spectral analysis of beat-to-beat data sampled for 30 min at four circadian times. Transgenic β₁TG4 mice showed an increase in 24 h heart rate, while blood pressure was not different from wildtype controls. Circadian patterns in blood pressure and heart were preserved in β₁TG4 mice. Addition of propranolol to the animals’ drinking water led to a reduction in heart rate and its 24 h variation in both strains of mice. Short-term variability in blood pressure was not different between wildtype and β₁TG4 mice, but heart rate variability in the transgenic animals showed a rightward shift of the high-frequency component in the nocturnal activity period, suggesting an increase in respiratory frequency. In conclusion, the present study shows that both the circadian and the short-term regulation of blood pressure and heart rate are largely preserved in young, nonfailing β₁-transgenic mice. This finding suggests that the loss of blood pressure and heart rate variability observed in human congestive heart failure cannot be attributed solely to sympathetic overactivity but reflects the loss of adrenergic responsiveness to changes in the activity of the autonomic nervous system.     

Impact of Intermittent Apnea on Myocardial Tissue Oxygenation—A Study Using Oxygenation-Sensitive Cardiovascular Magnetic Resonance

Background

Carbon dioxide (CO₂) is a recognized vasodilator of myocardial blood vessels that leads to changes in myocardial oxygenation through the recruitment of the coronary flow reserve. Yet, it is unknown whether changes of carbon dioxide induced by breathing maneuvers can be used to modify coronary blood flow and thus myocardial oxygenation. Oxygenation-sensitive cardiovascular magnetic resonance (CMR) using the blood oxygen level-dependent (BOLD) effect allows for non-invasive monitoring of changes of myocardial tissue oxygenation. We hypothesized that mild hypercapnia induced by long breath-holds leads to changes in myocardial oxygenation that can be detected by oxygenation-sensitive CMR.

Methods and Results

In nine anaesthetized and ventilated pigs, 60s breath-holds were induced. Left ventricular myocardial and blood pool oxygenation changes, as monitored by oxygenation-sensitive CMR using a T2*-weighted steady-state-free-precession (SSFP) sequence at 1.5T, were compared to changes of blood gas levels obtained immediately prior to and after the breath-hold. Long breath-holds resulted in an increase of paCO₂, accompanied by a decrease of paO₂ and pH. There was a significant decrease of blood pressure, while heart rate did not change. A decrease in the left ventricular blood pool oxygenation was observed, which was similar to drop in SaO₂. Oxygenation in the myocardial tissue however, was maintained throughout the period. Changes in myocardial oxygenation were strongly correlated with the change in paCO₂ during the breath-hold (r = 0.90, p = 0.010).

Conclusion

Despite a drop in blood oxygen levels, myocardial oxygenation is maintained throughout long breath-holds and is linearly correlated with the parallel increase of arterial CO₂, a known coronary vasodilator. Breathing maneuvers in combination with oxygenation-sensitive CMR may be useful as a diagnostic test for coronary artery function.     

Infusions of chemicals into the brain and the development of sustained elevations of blood pressure in the rat

Osmotic minipumps were used to infuse carbachol chloride (1.23 μg/hr), echothiophate iodide (0.5 μg/hr), histamine dihydrochloride (10 μg/hr), prostaglandin E₂ (1.0 μg/hr) and thyrotropin-releasing hormone (0.5 and 5.0 μg/hr) solutions into the cerebral ventricles of unanesthetized rats and blood pressure was measured by the tail-cuff method. Histamine dihydrochloride, prostaglandin E₂ and thyrotropin-releasing hormone produced an initial rise in blood pressure, but were not effective in producing sustained elevations in blood pressure. Carbachol infusions elevated blood pressure throughout the 7-day infusion period when results were compared to saline-infused animals. Infusions of echothiophate iodide, an anticholinesterase agent, produced an initial rise in blood pressure but these pressor effects were not sustained. In animals infused with echothiophate for 7 days, the pressor response to a challenge dose of echothiophate was diminished.