Inhibition of endotoxin-induced pulmonary vasoconstriction in dogs by alpha-methyl dopa

1963 ◽  
Vol 204 (6) ◽  
pp. 987-990 ◽  
Author(s):  
J. Albrecht Koehler ◽  
Theofilos J. Tsagaris ◽  
Hiroshi Kuida ◽  
Hans H. Hecht
Keyword(s):  
Venous Hypertension ◽  
Serotonin Synthesis ◽  
Vascular Effects ◽  
E Coli ◽  
Group Of Seven ◽  
Pulmonary Vasoconstriction ◽  
Portal Venous Hypertension ◽  
Physiologic Parameters ◽  
Pulmonary Arterial ◽  
Antihistaminic Drug

The demonstration in a previous study of the effectiveness of an antihistaminic drug in blocking some of the systemic but not the pulmonary vascular effects of endotoxin led to the study of the effect of an inhibitor of serotonin synthesis, alpha-methyl 3,4-dihydroxyphenylalanine (α-m dopa). One group of seven dogs was pretreated with a single dose of 250 mg, and a second group of six animals with three doses of 250 mg, each given at 10-min intervals. Results in these two groups were compared with those in six control animals. Purified E. coli endotoxin, 1 mg/kg, was administered intravenously in all 19 experiments. Intravenous administration of α-m dopa alone had no effect on measured physiologic parameters. Compared with the endotoxin response in control animals, pretreatment with either dose level appeared to have no effect on the magnitude or duration of systemic arterial hypotension, portal venous hypertension, or drop in cardiac output. However, pretreatment with 250-mg and 750-mg doses was associated with significant reduction and abolition, respectively, of pulmonary arterial hypertension. The results are consistent with the interpretation that the pulmonary vasoconstrictive response to endotoxin is mediated through the release of serotonin and that α-m dopa blocks this response by interfering with the synthesis of this intermediary.

THE PHYSIOLOGICAL MECHANISMS OF THE PULMONARY VENOUS HYPERTENSION

2018 ◽  
Vol 18 (2) ◽  
pp. 7-18
Author(s):  
V I Evlakhov ◽  
I Z Poyassov ◽  
V I Ovsyannikov
Keyword(s):  
Pulmonary Hypertension ◽  
Venous Pressure ◽  
Pulmonary Veins ◽  
Left Ventricular ◽  
Venous Hypertension ◽  
Physiological Mechanisms ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
Mechanisms Of Development ◽  
Trigger Mechanisms

In the review regulatory mechanisms of functions of pulmonary venous vessels have been considered as well as the signifi cance of their impairment in the development of the pulmonary hypertension, caused by the left ventricular cardiac failure. One of the trigger mechanisms of the development of the pulmonary hypertension as a result of the elevation of the left atrial and pulmonary venous pressure is the reflectory constriction of the pulmonary arterioles (Kitayev’s reflex). Further, the development of endothelial dysfunction and pulmonary vessels remodeling with the phenomenon of “arterializations” of the pulmonary veins take place. The exact evaluation of the pulmonary vascular resistance value in the clinical practice is a difficult task. This parameter, being integrated, does not allow to evaluate the resistance values of pulmonary arterial and venous vessels in the conditions of pulmonary hypertension and to give exact characteristics of their changes, as a result. The mechanisms of development of the pulmonary venous hypertension could not be explicated using the simplified model of the pulmonary vasoconstriction, because the main features of the pulmonary circulation are the presence of arteriovenous and bronchopulmonary shunts, and pulsatile character of the blood flow. To understand the exact pathogenesis of this pathology the further fundamental investigation not only on the cell level, but also on organ and system levels are needed.

Pulmonary vascular impedance vs. resistance in hypoxic and hyperoxic dogs: effects of propofol and isoflurane

1993 ◽  
Vol 74 (5) ◽  
pp. 2188-2193 ◽  
Author(s):  
P. Ewalenko ◽  
C. Stefanidis ◽  
A. Holoye ◽  
S. Brimioulle ◽  
R. Naeije
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Vasculature ◽  
Hemodynamic Changes ◽  
Vascular Effects ◽  
Intravenous Anesthesia ◽  
Mean Pulmonary Arterial Pressure ◽  
Vascular Impedance ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
The Time Domain

The pulmonary vascular effects of inhaled anesthetics have been reported variably. We compared the effects of intravenous anesthesia (propofol) and inhalational anesthesia (isoflurane) on multipoint mean [pulmonary arterial pressure (Ppa)-pulmonary arterial occluded pressure (PpaO)]/cardiac output (Q) plots and on pulmonary vascular impedance (PVZ) spectra in eight dogs alternatively ventilated in hyperoxia [inspired O2 fraction (FIO2) 0.4] and in hypoxia (FIO2 0.1). Q was altered by a manipulation of venous return. During propofol, hypoxia increased (Ppa-PpaO) by an average of 2–3 mmHg over the entire range of Q studied, from 1 to 2.5 l.min-1 x m-2. This hypoxic pulmonary vasoconstriction (HPV) was associated with insignificant changes in PVZ. Decreasing Q in hypoxia and hyperoxia did not affect PVZ. Compared with propofol, isoflurane decreased (Ppa-PpaO) by an average of 2–5 mmHg at all levels of Q studied in both hypoxia and hyperoxia but did not affect HPV. During isoflurane anesthesia, 0 Hz PVZ was lower (P < 0.01) in hypoxia, but otherwise the PVZ spectrum was not different from that recorded during propofol anesthesia. We conclude that, in dogs, 1 degree general anesthesia with isoflurane alone decreases pulmonary vascular tone without inhibition of HPV and that 2 degrees pressure/Q plots in the time domain are more sensitive than those in the frequency domain to subtle hemodynamic changes induced by hypoxia or isoflurane at the periphery of the pulmonary vasculature.

Pulmonary arterial pressure-flow plots in dogs: effects of isoflurane and nitroprusside

1987 ◽  
Vol 63 (3) ◽  
pp. 969-977 ◽  
Author(s):  
R. Naeije ◽  
P. Lejeune ◽  
M. Leeman ◽  
C. Melot ◽  
T. Deloof
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Arachidonic Acid Metabolism ◽  
Minimal Alveolar Concentration ◽  
Vascular Effects ◽  
Pulmonary Vasoconstriction ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial ◽  
End Tidal

We investigated the effects of nitroprusside and isoflurane on multipoint pulmonary arterial pressure (PAP)/cardiac index (Q) plots in pentobarbital sodium-anesthetized dogs ventilated alternatively in hyperoxia (fraction of inspired O2, FIO2, 0.4) and hypoxia (FIO2 0.1). Over the entire range of Q studied, 2–5 l.min-1.m-2, hypoxia increased PAP in 16 dogs (“responders”) and did not affect PAP in 16 other dogs (“nonresponders”). A hypoxic pulmonary vasoconstriction (HPV) was restored in the nonresponders by intravenous administration of 1 g of acetylsalicylic acid (ASA). Nitroprusside (5 micrograms.kg-1.min-1) inhibited HPV in responders (n = 8) and nonresponders treated with ASA (n = 8). End-tidal 1.41% isoflurane (a minimal alveolar concentration equal to one for dogs) did not affect HPV in responders (n = 8) and nonresponders treated with ASA (n = 8). In the latter group isoflurane increased PAP at the highest Q studied (3–5 l.min-1.m-2) in hyperoxia and hypoxia. In a final group of eight dogs with Q kept constant, PAP remained unchanged during two consecutive sequences of alternated 30-min periods (maximum time to generate a PAP/Q plot) successively at FIO2 0.4 and 0.1, and the hypoxia-induced increase in PAP was reproducible. Thus the present experimental model appeared suitable for the study of the effects of hypoxia and drugs on pulmonary vascular tone of intact dogs. At the given doses HPV was inhibited by nitroprusside and not affected by isoflurane. Products of arachidonic acid metabolism possibly could be implicated in the pulmonary vascular effects of isoflurane.

Influence of promethazine on circulatory response to endotoxin in dogs

1963 ◽  
Vol 204 (6) ◽  
pp. 983-986 ◽  
Author(s):  
Fred L. Anderson ◽  
Hiroshi Kuida ◽  
Hans H. Hecht
Keyword(s):  
Standard Dose ◽  
Selective Inhibition ◽  
Endotoxin Shock ◽  
Venous Hypertension ◽  
Control Group ◽  
Group Of Seven ◽  
Adequate Dose ◽  
Circulatory Effects ◽  
Systemic Artery ◽  
Portal Venous Hypertension

Histamine has been implicated as an intermediary in the mechanism of experimental endotoxin shock. The effect of pretreatment with an antihistaminic drug, promethazine hydrochloride (PMZ), on the hemodynamic response to E. coli endotoxin was studied in a group of 13 anesthetized dogs. Results were compared with the characteristic effects of endotoxin obtained in six control animals. Parameters that were measured and evaluated for possible effects of pretreatment were as follows: systemic artery, pulmonary artery, and portal vein pressures; cardiac output; heart rate; and calculated systemic and pulmonary resistances. In six animals that received doses of PMZ ranging from 1 to 9 mg/kg, the responses to endotoxin were not significantly different from those in the control group. However, in a group of seven dogs pretreated with a standard dose of 20 mg/kg PMZ, a modified response was demonstrated consisting of significant reduction in the magnitude of early systemic hypotension and portal venous hypertension. Pulmonary hypertension was augmented. The results are consistent with the interpretation that certain circulatory effects of endotoxin are mediated through histamine and that these are partially amenable to selective inhibition by an adequate dose of an antihistaminic agent such as PMZ.

Pulmonary vascular responses to surgical chemodenervation and chemical sympathectomy in dogs

1989 ◽  
Vol 66 (1) ◽  
pp. 42-50 ◽  
Author(s):  
R. Naeije ◽  
P. Lejeune ◽  
M. Leeman ◽  
C. Melot ◽  
J. Closset
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Sham Operation ◽  
Chemical Sympathectomy ◽  
Vascular Effects ◽  
Peripheral Chemoreceptor ◽  
Pulmonary Vasoconstriction ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial ◽  
6 Hydroxydopamine ◽  
Final Group

We investigated the effects of surgical peripheral chemoreceptor denervation, chemical sympathectomy with 6-hydroxydopamine (6-OHDA), and the peripheral chemoreceptor stimulant almitrine on multipoint pulmonary arterial pressure-cardiac index (PAP/Q) plots in 30 pentobarbital sodium-anesthetized dogs ventilated alternatively in hyperoxia [fraction of inspired O2, (FIO2) = 0.4] and hypoxia (FIO2 = 0.1). A hypoxic pulmonary vasoconstriction (HPV), i.e., a hypoxia-induced increase in PAP over the entire range of Q studied, from 2 to 5 l.min-1.m-2, was elicited in all the animals. Surgical denervation of the carotid and aortic chemoreceptors in a first group of nine dogs increased PAP at the lowest Q of 2 and 3 l.min-1.min-2 in hyperoxia and increased PAP at all levels of Q in hypoxia, so that HPV was enhanced. Chemical sympathectomy in a second group of eight dogs increased PAP at all levels of Q to a comparable extent in hyperoxia and hypoxia so that HPV remained unchanged. Almitrine (8 micrograms.kg-1.min-1 iv) in a third group of eight dogs increased PAP at all levels of Q in hyperoxia but had no effect on PAP/Q plots in hypoxia, so that HPV was inhibited. Almitrine had these same pulmonary vascular effects when administered to the chemodenervated and the sympathectomized dogs. Sham operation and a 2-h delay in a final group of five dogs had no effect on hyperoxic or hypoxic PAP/Q plots. We conclude that in intact dogs 1) the sympathetic nervous system reduces both hyperoxic and hypoxic pulmonary vascular tone, 2) stimulation of the peripheral chemoreceptors inhibits HPV, and 3) almitrine has direct pulmonary vasoconstricting effects in hyperoxia but not hypoxia.

Pulmonary and systemic vascular effects of SRS-A blockade in conscious lambs

1985 ◽  
Vol 249 (5) ◽  
pp. H968-H973
Author(s):  
T. J. Kulik ◽  
R. K. Schutjer ◽  
D. F. Howland ◽  
J. E. Lock
Keyword(s):  
Arterial Pressure ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Systemic Resistance ◽  
Adrenergic Blockade ◽  
Vascular Effects ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial

There is preliminary evidence suggesting that hypoxic pulmonary vasoconstriction may be mediated by slow-reacting substance of anaphylaxis (SRS-A), which is comprised of leukotrienes C4, D4, and E4. We studied the effects of the SRS-A antagonist FPL 57231 (FPL) on the hypoxic pulmonary vasoconstrictor response and on systemic vascular resistance in awake, chronically instrumented young lambs. Two other studies were performed to ascertain whether FPL's vasodilation was specific for hypoxic pulmonary vasoconstriction: the effect of FPL infusion in pulmonary and systemic vascular resistance was measured in six normoxic lambs, and the effect of FPL on 5-hydroxytryptamine (5-HT)-mediated vasoconstriction was determined. In seven lambs, mean pulmonary arterial pressure was 21 mmHg in room air and 28 mmHg in hypoxia (Po2 = 43 Torr). During hypoxia, FPL infusion (2 mg X kg-1 X min-1) reversibly decreased pulmonary arterial pressure to 15 mmHg; pulmonary arteriolar resistance also fell below normoxia levels with FPL. FPL also caused a fall in aortic pressure and systemic vascular resistance in these hypoxic lambs, but the decrease in systemic resistance was less than the fall in pulmonary resistance. beta-Adrenergic blockade using propranolol (1 mg/kg) did not affect the pulmonary vasodilation caused by FPL. In six normoxic lambs, FPL infusion also significantly decreased pulmonary and systemic vascular resistance (29% in each case). These data are consistent with the idea that leukotrienes may be involved in adjusting both pulmonary and systemic vascular tone, but further work is necessary to establish whether FPL's vasodilation is mediated via its leukotriene antagonism or is a nonspecific effect of FPL.

PAF increases vascular permeability without increasing pulmonary arterial pressure in the rat

2001 ◽  
Vol 90 (1) ◽  
pp. 261-268 ◽  
Author(s):  
Leonardo C. Clavijo ◽  
Mary B. Carter ◽  
Paul J. Matheson ◽  
Mark A. Wilson ◽  
William B. Wead ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Edema ◽  
Pulmonary Arterial Pressure ◽  
Ex Vivo ◽  
Platelet Activating Factor ◽  
Microvascular Permeability ◽  
Blue Dye ◽  
E Coli ◽  
Pulmonary Arterial

In vivo pulmonary arterial catheterization was used to determine the mechanism by which platelet-activating factor (PAF) produces pulmonary edema in rats. PAF induces pulmonary edema by increasing pulmonary microvascular permeability (PMP) without changing the pulmonary pressure gradient. Rats were cannulated for measurement of pulmonary arterial pressure (Ppa) and mean arterial pressure. PMP was determined by using either in vivo fluorescent videomicroscopy or the ex vivo Evans blue dye technique. WEB 2086 was administered intravenously (IV) to antagonize specific PAF effects. Three experiments were performed: 1) IV PAF, 2) topical PAF, and 3) Escherichia coli bacteremia. IV PAF induced systemic hypotension with a decrease in Ppa. PMP increased after IV PAF in a dose-related manner. Topical PAF increased PMP but decreased Ppa only at high doses. Both PMP (88 ± 5%) and Ppa (50 ± 3%) increased during E. coli bacteremia. PAF-receptor blockade prevents changes in Ppa and PMP after both topical PAF and E. coli bacteremia. PAF, which has been shown to mediate pulmonary edema in prior studies, appears to act in the lung by primarily increasing microvascular permeability. The presence of PAF might be prerequisite for pulmonary vascular constriction during gram-negative bacteremia.

PKC activates BKCa channels in rat pulmonary arterial smooth muscle via cGMP-dependent protein kinase

2004 ◽  
Vol 286 (6) ◽  
pp. L1275-L1281 ◽  
Author(s):  
Scott A. Barman ◽  
Shu Zhu ◽  
Richard E. White
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Channel Activity ◽  
Sprague Dawley ◽  
Dependent Protein Kinase ◽  
Pulmonary Vasoconstriction ◽  
Sprague Dawley Rat ◽  
Dependent Protein ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Smooth Muscle

Normally, signaling mechanisms that activate large-conductance, calcium- and voltage-activated potassium (BKCa) channels in pulmonary vascular smooth muscle cause pulmonary vasodilatation. BKCa-channel modulation is important in the regulation of pulmonary arterial pressure, and inhibition (decrease in the opening probability) of the BKCa channel has been implicated in the development of pulmonary vasoconstriction. Protein kinase C (PKC) causes pulmonary vasoconstriction, but little is known about the effect of PKC on BKCa-channel activity in pulmonary vascular smooth muscle. Accordingly, studies were done to determine the effect of PKC on BKCa-channel activity using patch-clamp studies in pulmonary arterial smooth muscle cells (PASMCs) of the Sprague-Dawley rat. The PKC activators phorbol myristate acetate (PMA) and thymeleatoxin opened BKCa channels in single Sprague-Dawley rat PASMC. The activator response to both PMA and thymeleatoxin on BKCa-channel activity was blocked by Gö-6983, which selectively blocks PKC-α, -δ, -γ, and -ζ, and by rottlerin, which selectively inhibits PKC-δ. In addition, the specific cyclic GMP-dependent protein kinase antagonist KT-5823 blocked the responses to PMA and thymelatoxin, whereas the specific cyclic AMP-dependent protein kinase blocker KT-5720 had no effect. In isolated pulmonary arterial vessels, both PMA and forskolin caused vasodilatation, which was inhibited by KT-5823, Gö-6983, or the BKCa-channel blocker tetraethylammonium. The results of this study indicate that activation of specific PKC isozymes increases BKCa-channel activity in Sprague-Dawley rat PASMC via cyclic GMP-dependent protein kinase, which suggests a unique signaling mechanism for vasodilatation.

Enhancement of the pulmonary vasoconstriction reaction to alveolar hypoxia in systemic high blood pressure

1989 ◽  
Vol 76 (6) ◽  
pp. 589-594 ◽  
Author(s):  
Maurizio D. Guazzi ◽  
Marco Berti ◽  
Elisabetta Doria ◽  
Cesare Fiorentini ◽  
Claudia Galli ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Arterial Pressure ◽  
High Blood Pressure ◽  
Pulmonary Arterial Pressure ◽  
Systemic Hypertension ◽  
Pulmonary Vasoconstriction ◽  
Arteriolar Resistance ◽  
Alveolar Hypoxia ◽  
Pulmonary Arterial

1. In systemic hypertension the pulmonary vessels show an excessive tone at rest and hyper-react to adrenoceptor stimulation. Alterations in Ca2+ handling by the vascular smooth muscle cells seem to underlie these disorders. Alveolar hypoxia also constricts pulmonary arteries, increasing the intracellular Ca2+ availability for smooth muscle contraction. This suggests the hypothesis that hypoxic pulmonary vasoconstriction depends on similar biochemical disorders, and that the response to the hypoxic stimulus may be emphasized in high blood pressure. 2. In 21 hypertensive and 10 normotensive men, pulmonary arterial pressure and arteriolar resistance have been evaluated during air respiration and after 15 min of breathing 17, 15 and 12% oxygen in nitrogen. Curves relating changes in pulmonary arterial pressure and arteriolar resistance to the oxygen content of inspired gas had a similar configuration in the two populations, but in hypertension were steeper and significantly shifted to the left of those in normotension, reflecting a lower threshold and an enhanced vasoconstrictor reactivity. 3. This pattern was not related to differences in severity of the hypoxic stimulus, degree of hypocapnia and respiratory alkalosis induced by hypoxia, and plasma catecholamines. 4. The association of high blood pressure with enhanced pulmonary vasoreactivity to alveolar hypoxia could have clinical implications in patients who are chronically hypoxic and have systemic hypertension.

Sign in / Sign up

Export Citation Format

Share Document