Effects Of Vasoactive Substances Research Articles

Passage of low density lipoproteins through monolayers of human arterial endothelial cells. Effects of vasoactive substances in an in vitro model.

The endothelium controls the influx of lipoproteins into the arterial wall, a process that may be disturbed in arteriosclerotic blood vessels. We have used an in vitro model to investigate the characteristics of the passage of low density lipoproteins (LDL) through monolayers of human arterial endothelial cells. Umbilical artery, aorta, or carotid artery endothelial cells were cultured on polycarbonate filters and formed a tight monolayer in which the cells were connected by tight junctions. Passage of 125I-LDL through these monolayers proceeded linearly over a 24-hour period. It was threefold lower through monolayers of aorta or carotid artery cells than through monolayers of umbilical artery cells. The LDL passage process did not show saturation with LDL concentrations up to 800 micrograms/ml LDL-protein (i.e., 1.6 nmol/ml apolipoprotein B) between 2 and 4 hours after addition. However, during the first 30 to 60 minutes after addition of high concentrations of LDL, a reduction of the passage rate of both LDL and peroxidase, resulting in an apparent saturation of the passage process, was observed. The passage rate of the negatively charged acetylated LDL was twofold lower than that of native LDL. Addition of histamine to the endothelial monolayer resulted in a large, but transient, increase in permeability paralleled by a decrease in electrical resistance. The effects of histamine were mediated via an H1 receptor. Thrombin and Ca++ ionophore also induced an increase in permeability of the monolayer, while bradykinin did not. The effects of histamine and thrombin were paralleled by a rapid and marked increase in cytoplasmatic Ca++ concentration of the endothelial cells, while bradykinin induced only a small increase. Although the cyclic adenosine 5'-monophosphate-elevating agent, forskolin, markedly decreased the basal rate of LDL passage through the endothelial cell monolayers, it did not change the relative increase in permeability induced by histamine. Thus, histamine induces small, but significant, increases in the permeability of tight endothelial cell monolayers.

Effect of vasoactive substances on natriuresis induced by atrial natriuretic peptide in isolated perfused rat kidneys.

We studied the interaction between synthetic atrial natriuretic peptide (ANP) and various vasoactive substances, which included isoproterenol (ISO), aminophylline (AMI), and dibutyryl cyclic AMP (dBcAMP) as vasodilators, and angiotensin II (AII) and norepinephrine (NE) as vasoconstrictors, and prazosin as an alpha-blocker in isolated perfused rat kidneys (IPK). When 10(-9) mol of ANP was administered in 75 ml of a perfusate, the renal vascular resistance (RVR) was transiently decreased for 5 min, and increased thereafter. Simultaneously, ANP increased the glomerular filtration rate (GFR), urine flow (UV), absolute Na excretion (UNaV) and absolute K excretion (UKV). All of the above mentioned effects of ANP were significantly inhibited by administering ISO, AMI or dBcAMP. On the other hand, the administration of AII and NE significantly enhanced the increases in UV and UNaV and the fractional excretion of Na induced by ANP, although AII and NE had no influence on the changes in RVR and GFR induced by ANP. Prazosin did not modify the renal effects of ANP. These results suggest that the natriuretic effect of ANP is inhibited by agents that increase cyclic AMP in vascular smooth muscle cells. It is also suggested that the natriuretic effects of ANP can be explained by an increase in GFR and changes in intrarenal hemodynamics, rather than by the direct effect of ANP on renal tubules.

A Method for Studying the Effect of Vasoactive Substances on Glomerular Filtration Without Affecting the Central Haemodynamics

A method for microcatheterization of rat kidneys was developed. The catheter consists of 50-100 micron thick polyethylene tubes, and is inserted into the interlobular or arcuate arteries via a lumbar artery. The technique makes it possible to perfuse a small number of nephrons with very high doses of vaso active substances without affecting the nephrons in the vicinity or the central haemodynamics. By adding labelled inulin to the perfusate it is also possible to calculate the amount of drug reaching the nephron under study. It was shown that the catheterization and perfusion with Ringer solution per se have no effect on the nephron function. Perfusion with very high doses of acetylcholine was found to have a selective effect on the area perfused but caused no changes in central haemodynamics, or on nephrons in unperfused areas. It is concluded that the technique is suitable for use in studies concerning the handling of high doses of vasoactive substances by the nephron.

Microcirculatory methods for evaluating the effect of vasoactive drugs in clinical practice.

Microcirculatory methods have to be used in order to be able to evaluate the effect of vasoactive drugs in ischemic skin areas. During the past two decades several new such techniques for studying the microcirculation in man have been developed. These techniques have shown to be of great value for evaluating drug effects in patients with disturbed peripheral circulation. One such method is the non-invasive Laser Doppler technique. It measures both the nutritional and the non-nutritional thermoregulatory vascular bed of the skin. The data achieved are only semiquantitative, but the method has been shown to be clinically very useful for studying the dynamics of total skin microcirculation in a specific area. In order to be able to study directly what happens in the nutritional capillaries microscopical methods have to be used. Two such techniques are available in clinical practice. By an ordinary light microscope the capillaries can be directly visualized. A specific classification system can be used to evaluate the degree of ischemic damage to an area. The effect of different kinds of therapeutic procedures for improving the microcirculation in an ischemic area can be easily evaluated. By the combination of a light microscope and a sensitive TV-camera the blood flow in single skin capillaries can be measured at a magnification of 250-1 000 times. This method is well suited for testing the immediate effects of vasoactive substances on the nutritional skin circulation both in healthy subjects and in patients with different kinds of cardiovascular diseases.

The effects of noradrenaline, B-HT 920, methoxamine, angiotensin II and vasopressin on mean circulatory filling pressure in conscious rats.

The effects of vasoactive substances on mean circulatory filling pressure (MCFP), an index of total body venous tone, were determined in conscious rats. Cumulative doses of saline (0.9% w/v NaCl solution), methoxamine (alpha 1-adrenoceptor agonist), B-HT920 (alpha 2-adrenoceptor agonist) noradrenaline and vasopressin, and individual doses of angiotensin II (AII), were infused into the rats. Mean arterial pressure (MAP), MCFP and heart rate (HR) were determined before and during the plateau responses to infusions of the vasoactive substances. The infusions of all the agonists caused a dose-dependent increase in MAP and a decrease in HR. The infusion of saline affected neither MAP nor HR. The infusions of saline and methoxamine did not affect MCFP while the infusions of B-HT 920, noradrenaline and AII increased MCFP. MCFP was slightly increased during the infusion of high doses of vasopressin. It was concluded that receptors for the alpha 2-adrenoceptor agonist and AII are involved in the control of venous tone. Receptors for the alpha 1-adrenoceptor agonist and vasopressin are not important for the control of venous tone.

Synergistic action of angiotensin II on norepinephrine-induced prostaglandin release from rat glomeruli.

The effects of vasoactive substances on the release of prostaglandin (PG) and thromboxane (TX) from isolated rat glomeruli were investigated. The PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and TXB2 release during 60 min into Krebs-Henseleit medium was assessed by radioimmunoassay following extraction. Norepinephrine (NE) stimulated PGE2 (from 2,117 +/- 117 to 3,968 +/- 182 pg X mg protein-1 X 60 min-1, P less than 0.01) at a concentration of 10(-4)M and PGF2 alpha (from 2,748 +/- 285 to 8,535 +/- 495 pg X mg protein-1 X 60 min-1, P less than 0.01) at a concentration of 10(-5)M. However, neither angiotensin II (ANG II) nor arginine vasopressin (AVP) affected the release of PG and TXB2 at concentrations up to 10(-5)M. In the presence of 10(-5) M NE, ANG II enhanced the release of PGE2 (from 3,307 +/- 207 to 6,865 +/- 469 pg X mg protein-1 X 60 min-1., P less than 0.01) and PGF2 alpha (from 3,652 +/- 252 to 6,612 +/- 388 pg X mg protein-1 X 60 min-1, P less than 0.01) at a concentration of 10(-8)M, whereas AVP lacked any similar effect. These results indicate that catecholamine acts as a major stimulant for the release of PG from isolated glomeruli via alpha-receptors. ANG II may work in cooperation with catecholamine, but AVP appears to play little role.

Alterations in vascular sensitivity to vasoactive agents after discontinuation of propranolol in SHR.

Spontaneously hypertensive rats (SHR) were treated with propranolol (P) (70 mg/kg) daily for 2 or 4 weeks and then the effects of vasoactive substances on blood pressure were studied 10 or 36 hours after the last dose of P. At 10 hours after the last dose of P, vascular hyperresponsiveness to norepinephrine (NE) and angiotensin II (AII) had largely disappeared, but the hypotensive action of isoproterenol and prostacyclin was still blocked in P-treated SHR. An increase of cyclic AMP (cAMP) in response to isoproterenol was blocked in the thoracic aorta. Similarly, an increase of circulating cAMP and blood glucose in response to epinephrine (E) was depressed. At 36 hours after the last dose of P, an elevation of blood pressure in response to NE and AII was significantly reduced in P-treated SHR. Although basal blood pressure with or without anesthesia was the same in P-treated SHR and control SHR, a decrease of blood pressure in response to isoproterenol and prostacyclin was augmented significantly in P-treated SHR. This was also true in normal rats similarly treated. In addition, an increase of cAMP in the thoracic aorta in response to isoproterenol and prostacyclin was augmented significantly in P-treated SHR. An increase in blood glucose in response to E was not blocked, but an increase of circulating cAMP in response to E was blocked. These data suggest that cAMP synthesis in the vessels is somehow related to the production of peculiar vascular responses during escape from P action.(ABSTRACT TRUNCATED AT 250 WORDS)

P-433) - Effects of vasoactive substances and secretagogues on the saturation of tissue oxygen (SO2) in rat gastric mucosa

P-433) - Effects of vasoactive substances and secretagogues on the saturation of tissue oxygen (SO2) in rat gastric mucosa

Assessment of the effect of drugs on the venous system in man.

Any generalized constriction or dilatation of the systemic venous bed must necessarily result in changes in central venous pressure, and the effect of vasoactive substances on the veins is, in consequence, an important determinant of their action on the circulation as a whole.

Effect of Vasoactive Substances on Cyclic Nucleotide Contents of Guinea-pig Lung and Tracheal Tissues

Effect of Vasoactive Substances on Cyclic Nucleotide Contents of Guinea-pig Lung and Tracheal Tissues

Effect of vasoactive substances on the cyclic nucleotide contents of guinea-pig lung and tracheal tissues. 1. Basic investigations (author's transl)

Effect of vasoactive substances on the cyclic nucleotide contents of guinea-pig lung and tracheal tissues. 1. Basic investigations (author's transl)

Effect of Vasoactive Substances on the Cyclic Nucleotide Contents of Guinea-pig Lung and Tracheal Tissues

Effect of Vasoactive Substances on the Cyclic Nucleotide Contents of Guinea-pig Lung and Tracheal Tissues

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

Metabolism and Effects of Vasoactive Substances in the Lung

The influence of histamine and other vasoactive substances on contractile responses of cat skeletal muscle to acetylcholine.

1. The effect of vasoactive substances, chiefly histamine, on contractions of cat skeletal muscle evoked by acetylcholine has been studied. For this purpose all of these agents were administered intra-arterially to anterior tibialis, chiefly, and also to soleus and external rectus muscles in vivo.2. Under these conditions, histamine itself never altered the resting tension of the muscle, but always enhanced the increase in tension produced by acetylcholine injected shortly afterward.3. On the anterior tibialis muscle, it was determined that the threshold potentiating dose of histamine was 0.001 mug/kg, and that maximal enhancement occurred when 0.1 mug/kg was injected 15 s before fixed, submaximal doses of acetylcholine. Injected 15 s before graded doses of acetylcholine, histamine 0.1 mug/kg shifted the acetylcholine dose-response curves approximately 1.5 log units to the left.4. Under similar experimental conditions the vasodilator, bradykinin, 0.001-1 mug/kg, and procedures which produce a local increase in nutritive capillary blood flow also enhanced acetylcholine-evoked contractile responses of the anterior tibialis, whereas the vasoconstrictor, angiotensin, 0.001-1 mug/kg, inhibited them.5. The potentiating effect of histamine was antagonized by mepyramine, but was undiminished by denervation of the muscle either acutely or for 4 days.6. Histamine failed to enhance responses of the muscle to electrical stimulation of either the muscle, directly, or its motor nerve.7. Histamine also had no effect upon acetylcholine-evoked responses of the isolated external rectus muscle in vitro.8. It is suggested that the potentiating effect of histamine in vivo is due to its vasodilator action within the muscles which, by relaxing arterioles and precapillary sphincters, could allow more of the blood-borne acetylcholine to reach more of its receptors on the muscle fibres in a given time.