Effects Of Vasoactive Substances Research Articles

CVRmap—a complete cerebrovascular reactivity mapping post-processing BIDS toolbox

Cerebrovascular Reactivity (CVR) refers to the ability of cerebral blood vessels to dilate or constrict under the effect of vasoactive substances and can be estimated using functional Magnetic Resonance Imaging (fMRI). Computation of CVR maps is relevant in various brain diseases and requires specialized data processing. We introduce CVRmap, an opensource software that automates the computation of CVR map. The toolbox complies with the Brain Imaging Data Structure (BIDS) standards.

Effects of vasoactive substances on biomechanics of small resistance arteries of male and female Dahl salt-sensitive rats.

Changes in vascular biomechanics leading to increase in arterial stiffness play a pivotal role in circulatory dysfunction. Our objectives were to examine sex-specific pharmacological changes related to the biomechanics and any structural modifications in small resistance arteries of Dahl salt-sensitive male and female rats. The composite Young modulus (CYM) was determined using pressure myograph recordings, and immunohistochemistry was used for the evaluation of any structural changes in the third-order mesenteric arteries (n = 6). Animals on high-salt diet developed hypertension with significant elevation in central and peripheral blood pressures and pulse wave velocity compared to those on regular diet. There were no significant differences observed in the CYM between any of the groups (i.e., males and females) in vehicle-treated time-control studies. The presence of verapamil (0.3 μM) significantly reduced CYM in hypertensive males without changes within females compared to vehicle. This effect was abolished by phenylephrine (0.3 μM). BaCl2 (100 μM), ouabain (100 μM), and L-NAME (0.3 μM) combined significantly increased CYM in vessels from in normotensive males and females but not in hypertensive males compared to vehicle. The increase in CYM was abolished in the presence of phenylephrine. Sodium nitroprusside (0.3 μM), in the presence of phenylephrine, significantly reduced CYM in male normotensive versus hypertensive, with no differences within females. Significant differences were observed in immunohistochemical assessment of biomechanical markers of arterial stiffness between males and females. Our findings suggest sex possibly due to pressure differences to be responsible for adaptive changes in biomechanics, and varied pharmacological responses in hypertensive state.

Target temperature management of 33°C exerts benefi cial haemodynamic eff ects after out-of-hospital cardiac arrest

Background Accumulating evidence indicates that target temperature management (TTM) is benefi cial in patients resuscitated after cardiac arrest since it appears to improve neurological outcome. However, the optimal cooling method (surface vs intravascular) has not yet been specifi ed. Substantial heart disease is present in most of these patients and therefore haemodynamic eff ects of cooling need to be considered very carefully. We analysed the haemodynamic response to TTM in patients treated with surface versus intravascular cooling following out-of-hospital cardiac arrest.Methods and results In this observational study 63 consecutive subjects presenting to the hospital after successful resuscitation following of out-of-hospital cardiac arrest received an intravascular (40 patients) or external cooling device (23 patients) to induce TTM. While with intravascular cooling the target temperature of 33°C was reached after 159 minutes, the minimum temperature achieved with surface cooling was about 35°C after 437 minutes. Haemodynamic parameters were recorded in a 4-hour rhythm for the fi rst 12 hours after induction of hypothermia. Generally, TTM of 33°C resulted in a higher systemic vascular resistance index (749 vs 467 dyn*sec/cm5/m²; P= 0.04) but also in a marked reduction of heart rate (67.70 vs 100.00 bpm; P < 0.001), a higher mixed venous oxygen saturation (76 vs 68%; P= 0.016), and a higher stroke volume index (45 vs 33 ml/m²; P= 0.036). TTM additionally resulted in a higher cardiac power index (0.55 vs 0.46 Watt/m²; P= 0.024).Conclusion TTM of 33°C compared to 35°C exerts benefi cial haemodynamic eff ects and might be viewed as an adjunct inotropic therapy avoiding the undesired side eff ects of vasoactive substances.

Investigation of blood flow and the effect of vasoactive substances in cutaneous blood vessels of Xenopus laevis.

In the present study, a preparation of frog skin was presented, which can be used to demonstrate the basic concepts of blood flow regulation in a very clear and attractive way to high school and university students. In a freshly euthanized Xenopus, a patch of abdominal skin was exposed from the internal side and viewed with a USB microscope while it remained connected to a functioning circulatory system. In this way, it was possible to obtain sharp images of arteries and veins and to visualize blood flow. This allows students to learn about the functional differences between arteries and veins and about the complexity of hemodynamics as well as the particularities of the amphibian pulmocutaneous circulation. Students can then quantitatively estimate the effect of norepinephrine and epinephrine on the diameter of blood vessels by simply superfusing the skin patch with a series of solutions of the two substances. They can also test the effect of α-adrenergic receptor blockers, used to treat high blood pressure, on the norepinephrine-induced muscle tonus of blood vessels.

Pulmonary vascular and airway responses to systemic vasoconstrictors in anesthetized BALB/c mice.

There is no systematic study in which the effects of vasoactive substances were investigated on pulmonary vascular resistance (PVR) in in vivo mouse by directly measuring cardiac output and the inflow and outflow pressures in the pulmonary circulation. We determined the responses of PVR, total peripheral resistance (TPR), and airway pressure (AWP) to angiotensin II, endothelin-1, vasopressin, phenylephrine, and thromboxane A2 analog U46619 in anesthetized BALB/c mice. Pulmonary arterial pressure, left atrial pressure (LAP), and aortic blood flow were measured. TPR increased dose-dependently in response to consecutive administration of all vasoconstrictors except vasopressin which reduced TPR at the highest dose of 100 nmol/kg. At high doses of vasoconstrictors, pulmonary arterial pressure and AWP increased due to increased LAP, as demonstrated by the separate LAP elevation experiments. When LAP transiently increased at high doses, PVR did not increase but decreased. Nonetheless, enodothelin-1, angiotensin II, and U46619 increased PVR. Vasopressin at 100 nmol/kg increased AWP without LAP elevation. In conclusion, the high doses of the vasoconstrictors studied here exert indirectly a transient pulmonary vasodilatory and AWP increasing actions due to pulmonary congestion evoked by strong systemic vasoconstriction. Nevertheless, enodothelin-1, angiotensin II, and U46619 cause pulmonary vasoconstriction, and vasopressin constricts airway in anesthetized BALB/c mice.

CARDIOVASCULAR EFFECTS OF VASOACTIVE SUBSTANCES IN PROLONGED ANESTHESIA IN DOGS

Knowledge of the influence of anesthesia in anesthetized animals at in vivo experiments is essential in order to interpret the results of investigations properly and correctly. In this study we researched cardiovascular effects of vasoactive substances (adrenalin, noepinephrine, dimethylphenylpiperazinium, acethylholin, histamine) in prolonged anesthesia of six hours in dogs. The cardiovascular effects of vasoactive substances were evaluated by direct blood pressure measurement, ecg monitoring and urine output measurement. The dose-effect curve of systolic (SAP) and diastolic (DAP) blood pressure were obtained for each of the vasoactive substances. The differences between cardiovascular effects of vasoactive substances at the beginning and at the end of prolonged anesthesia were tested. There were statistically significant differences (p&lt;0.05) in changes of blood pressure at the beginning and at the end of prolonged anesthesia only for some doses of adrenalin and histamine (1 mg/kg and 3 mg/kg). No significant changes in heart rhythms at the beginning and at the end of prolonged anesthesia were recorded. The urine output during anesthesia depended on applied vasoactive substances.

Effects of vasoactive substances on the neurovascular structures and microcirculation in the developing callus 10 and 15 days after bone injury

The developing callus requires sufficient oxygen and substrate supply. Despite the importance of these processes, we have limited understanding of regulation of the callus microcirculation. We aimed to assess the role of vasoactive substances in the microcirculation of the callus in a gap osteotomy model in the rabbit detected by laser-Doppler flowmetry. The reactions were elicited with locally applied vasoactive substances: epinephrine (E), calcitonine-gene related protein (CGRP), substance P (SP), sodium nitroprusside (SNP) and Ebrantil (Ebr) on the 10th and 15th postoperative days. Changes of the circulatory parameters were compared to changes in the ipsilateral femoral bone marrow. Perfusion pressure, maximal change of the blood flow and 50% recovery time (50RT) of the flow reactions and peripheral micro vascular resistance (MVR) was calculated. Systemic blood pressure (BP) was measured directly with an arterial catheter. Reactive neurovascular structures, sensitive to neuropeptides and vasoactive substances, appear at a very early stage of callus formation. On the 10th postoperative day, 2/3 of the blood flow velocity of the intact tibia has already returned, and the values are higher on the 15th postoperative day than those of the intact tibia. The basal blood flow velocities (prior to administration of any substance) are significantly higher on the 15th postoperative day than on the 10th.

Coexisting Hepatopulmonary Syndrome and Portopulmonary Hypertension

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) represent pulmonary complications of liver disease and portal hypertension. The underlying pathophysiology behind these entities is complex and involves different effects of vasoactive substances on the pulmonary vasculature, among them endothelin-1 and nitric oxide (NO). Hepatopulmonary syndrome results from vasodilation, intrapulmonary shunting, and hypoxia. In contrast, portopulmonary hypertension is predominantly owing to generalized vasoconstriction that leads to remodeling and an increase in pulmonary vascular resistance, but is rarely associated with hypoxia. We present a case report in which these 2 processes with opposing pathologic mechanisms coexist in the same patient. We also conducted a literature search to identify other documented cases of coexisting hepatopulmonary syndrome and portopulmonary hypertension, common clinical features of these patients, and outcomes with or without treatment. Our case highlights the importance of recognizing the coexistence of these 2 disease processes, as they may occur simultaneously and affect the approach to treatment, including liver transplantation.

Effects of vasoactive substances on changes of pulmonary circulation in barium sulfate-induced pulmonary microembolism in the dog (author's transl)

Effects of vasoactive substances on changes of pulmonary circulation in barium sulfate-induced pulmonary microembolism in the dog (author's transl)

Effects of vasoactive substances on the canine airways and on pulmonary vascular bed (author's transl)

Effects of vasoactive substances on the canine airways and on pulmonary vascular bed (author's transl)

Effects of neuropeptides and vasoactive substances on microcirculation of the callus after tibial osteotomy in rabbits

Previous studies have demonstrated a dynamic ingrowth of vessels into the developing callus. In this study, maturation and development of the regulation of microcirculation were followed in the callus of rabbits. In the first series, the effects of vasoactive substances on blood flow velocity, perfusion pressure, duration of effects and peripheral vascular resistance of the bone marrow in the femur and tibia were compared. In the second series, the same parameters were measured in the femur and in the developing callus 10 and 15 days following gap osteotomy of the tibia. There were no significant differences between the microcirculatory reactions of the intact femur and tibia. Basal blood flow could be verified in the callus on the 10th postoperative day. No vascular reactions could be elicited. Basal blood flow velocity was higher on the 15th day, when compared to the measurements on the 10th day. The substances elicited statistically significant differences in flow velocity, resistance and 50% recovery time in the callus on the 15th day. Blood flow reactions of the ipsilateral femoral and tibial bone marrow are identical, thus the femur can serve as a reference site for blood flow measurements in the callus. Regulation and maturation of callus microcirculation develop rapidly between the 10th and 15th days.

Effects of norepinephrine and glyceryl trinitrate on cerebral haemodynamics: transcranial Doppler study in healthy volunteers

The effects of vasoactive substances on cerebral haemodynamics are not fully known. We studied the effects of norepinephrine and glyceryl trinitrate (GTN) on cerebral haemodynamics in healthy volunteers. The effects of norepinephrine (n=10) and GTN (n=10) on the middle cerebral artery flow velocity (MCAFV), cerebral autoregulation, reactivity to carbon dioxide, and estimated cerebral perfusion pressure (eCPP) were studied using transcranial Doppler ultrasound. Established methods were used for calculating zero flow pressure (ZFP). Measurements were made at baseline, and after i.v. infusion of the study drug to the endpoints of 25% increase in mean arterial pressure (MAP) for norepinephrine (0.02-0.1 microg kg(-1) min(-1)), or 15% decrease in MAP for GTN (0.5-2.5 microg kg(-1) min(-1)). The MCAFV remained unchanged with norepinephrine, but decreased slightly with GTN {from [median (inter-quartile range)] 53 (38, 62) to 48 (33, 52) cm s(-1)}. Cerebrovascular reactivity did not change significantly with either drug. The eCPP did not change significantly with norepinephrine, but increased significantly with GTN [from 49 (32, 54) to 62 (47, 79) mm Hg]. ZFP increased with norepinephrine [from 39 (28, 48) to 56 (46, 62) mm Hg] and decreased with GTN [from 35 (30, 49) to 12 (-7, 20) mm Hg]. Norepinephrine, despite increasing arterial pressure, did not increase the eCPP. The eCPP increased significantly with GTN, despite decreased MAP. Cerebral vascular tone is an important determinant of CPP during pharmacologically induced changes in arterial pressure.

Macrovascular Changes in Mice Overexpressing Human Semicarbazide-Sensitive Amine Oxidase in Smooth Muscle Cells

The catalytic activity of semicarbazide-sensitive amine oxidase (SSAO) is increased in diabetes, as well as in other disorders of cardiovascular origin. Our hypothesis is that SSAO is involved in the synthesis or maturation of elastin in vascular tissue. An increased SSAO activity can thereby be involved in the development of vascular damage. Elastin quantification was performed in aorta of transgenic mice overexpressing the human form of SSAO, using electron microscopy. Furthermore, lung capacity was measured using a spirometry-mimicking method, developed for mice. The effect of vasoactive substances was estimated by measuring mean arterial pressure and pulse pressure under anesthesia. No differences in elastin quantity or lung capacity could be observed between transgenic or nontransgenic littermates. Pulse pressure was higher in transgenic mice, and electron microscopy of aorta showed elastin fibers parallel with the aorta wall (ie, straight fibers instead of folded compared with control mice). No difference in the response to adrenaline or sodium chloride was observed between the transgenic and control mice. The control mice had a clear decrease in blood pressure (BP) with a longer duration as a response to injection of a nitric oxide (NO) donor, sodium nitroprusside, compared with transgenic mice where only a minor response was observed. The SSAO activity in serum of control mice was elevated in response to injection of the NO donor, but not in response to a ganglion blocker. An elevated pulse pressure, together with an abnormal elastin structure in the aorta, suggests a rigidity of large arteries as a result of an elevated SSAO activity as well as a physiologic role for SSAO in elastin maturation.

Alterations in transendothelial electrical resistance by vasoactive agonists and cyclic AMP in a blood-brain barrier model system.

We have previously reported that the co-culture of endothelial and glioma cell lines provides an in vitro model for investigating properties of the blood-brain barrier (BBB). To characterise the model system further we have investigated the effects of vasoactive substances implicated in increases in BBB permeability. Additionally, we have also examined whether activation of cyclic AMP signalling pathways, which elevate cerebral endothelial cell barrier function, similarly modulate our model system. ATP, histamine, bradykinin, and serotonin significantly decreased model BBB transendothelial electrical resistance and manipulations which elevate cyclic AMP enhanced culture resistance. These data indicate that our model BBB system responds in a manner characteristic of cerebral microvascular endothelial cells and the BBB in vivo. These data further emphasize the usefulness of our model system.

Innervation and effects of vasoactive substances in the coronary circulation.

Innervation and effects of vasoactive substances in the coronary circulation.

Vasodilation induced by vasopressin V2 receptor stimulation in afferent arterioles

We have previously reported that vasopressin (AVP) V2 receptor stimulation increased renal blood flow in dogs anesthetized with pentobarbital. In this study, we examined the direct effects of AVP on afferent arterioles to clarify the role played by V2 receptors in regulating afferent arteriolar tone. We microdissected a superficial afferent arteriole with glomerulus from the kidney of a New Zealand White rabbit. Each afferent arteriole was cannulated with a pipette system and microperfused in vitro at 60 mm Hg. The effects of vasoactive substances were evaluated by changes in the lumen diameter of afferent arterioles. We found that AVP decreased the lumen diameter of microperfused afferent arterioles dose-dependently and that a V1 antagonist, OPC21268, inhibited the vasoconstrictor action of AVP. However, AVP 10(-8) M increased the lumen diameter of norepinephrine (NE)-constricted afferent arterioles pretreated with OPC21268 (OPC + NE, 8.2 +/- 0.7 microns; OPC + NE + AVP, 9.9 +/- 0.9 microns*; *P < 0.05, N = 13). This vasodilatory effect of AVP was abolished by pretreatment with a V2 antagonist, OPC31260. Desmopressin (dDAVP), a V2 agonist, increased the lumen diameter of the NE-constricted afferent arterioles (NE, 7.4 +/- 0.9 microns; NE + dDAVP, 10.1 +/- 0.7 microns*; *P < 0.05, N = 9). These results suggest that AVP V2 receptors are present in rabbit afferent arterioles and that V2 receptor stimulation induces vasodilation in rabbit afferent arterioles.

Effects of vasoactive substances and cAMP related compounds on adrenomedullin production in cultured vascular smooth muscle cells

To elucidate the regulation mechanism of adrenomedullin (AM) production in blood vessels, we examined the effects of 30 substances on AM production in cultured rat vascular smooth muscle cells (VSMCs). Forskolin and 8-bromo-cAMP suppressed production and gene transcription of AM. Since VSMC expresses AM receptors coupled with adenylate cyclase, AM production may be regulated by intracellular cAMP concentration. Thrombin, vasoactive intestinal polypeptide and interferon-gg also inhibited AM production, while angiotensin II, endothelin-1, bradykinin, substance P, adrenaline, phorbol ester and fetal calf serum stimulated AM production in VSMC. These results suggest that AM production is regulated by a variety of substances, indicating complex systems regulating AM production.

Effect of vasoactive substances on membrane potentials in retinal microvascular pericytes

Intrathecal administration of prostaglandin E2 (PGE2) produces mechanical hyperalgesia, thermal hyperalgesia, and touch-evoked allodynia in rats. Experiments were conducted to examine the effects of intrathecal administration of relatively selective PGE2 receptor (EP receptor) agonists to establish which spinal EP receptors mediate these behavioral effects of spinally administered PGE2. Administration of either sulprostone (EP3 receptor agonist) or PGE1 alcohol (EP4 receptor agonist) produced marked mechanical and thermal hyperalgesia and touch-evoked allodynia. Neither 17-phenyl trinor PGE2 (EP1 receptor agonist) nor butaprost (EP2 receptor agonist) produced any significant changes in behavioral response thresholds to mechanical or thermal stimuli. However, 17-phenyl trinor PGE2 (EP1 receptor agonist) did produce marked touch-evoked allodynia. These data suggest that in rats activation of spinal EP3 and EP4 receptors by PGE2 is important for development of both mechanical and thermal hyperalgesia as well as for touch-evoked allodynia. PGE2-induced allodynia also appears to involve activation of spinal EP1 receptors.

Vasodilator therapy enhances neutrophil tissue migration

Very little is known about the effect of vasoactive substances on migration of polymorphonuclear neutrophils in vivo. We evaluated the effect of oral treatment with isosorbide dinitrate on neutrophil migration into a sterile skin inflammatory focus in man with the use of "skin chamber technique". Isosorbide dinitrate increased the number of neutrophils harvested in the chamber as well as the "granulocyte clearance". Thus, vasoactive agent may increase neutrophil extravasation and subsequent tissue migration.

Contractile and relaxant responses of the canine isolated spinal artery to vasoactive substances

1. Effects of vasoactive substances were investigated in the canine isolated spinal branch of the intercostal artery (SBICA). 2. Addition of angiotensin II (AII), vasopressin, noradrenaline (NA), adrenaline, 5-hydroxytryptamine (5-HT), and dopamine each produced concentration-dependent contraction in the SBICA, whereas prostaglandin F2 alpha, histamine, and tyramine caused only slight contraction. The decreasing order of the potency of contractile agents was AII much greater than vasopressin = NA greater than 5-HT greater than adrenaline much greater than dopamine. 3. Although the pD2 value for phenylephrine (5.31 +/- 0.36) was smaller than that for NA (6.48 +/- 0.13), there was no significant difference in Emax value between these two agonists in the SBICA. On the other hand, xylazine produced only a slight contraction, the pD2 value being 3.59 +/- 0.08. Phentolamine (10(-8)-10(-6) M) and prazosin (10(-8)-10(-6) M) competitively inhibited the NA-induced contraction, while yohimbine (10(-8)-10(-6) M) did not. 4. Acetylcholine (ACh), sodium nitroprusside (SNP), ATP, ADP, and adenosine caused concentration-dependent relaxations in SBICA following contraction with NA. On the other hand, isoprenaline up to 10(-4) M did not produce any relaxation. The decreasing order of potency of the relaxant agents was ACh greater than SNP much greater than ATP = ADP = adenosine. 5. The ACh-induced relaxation was competitively inhibited by atropine and was abolished by mechanical removal of the endothelium. Aspirin (5 x 10(-5) M) did not affect the relaxant response to ACh, while oxyhaemoglobin (10(-5) M) and methylene blue (10(-5) M) produced significant attenuation. 6. These results suggest that NA produces contraction of the isolated canine SBICA which is mainly mediated via alpha 1-adrenoceptors and that ACh causes a relaxation of the SBICA due to release of endothelium-derived relaxing factor (EDRF) from the endothelial cells.