Pulmonary and systemic blood pressure response to serotonin: role of chemoreceptors

1961 ◽  
Vol 201 (2) ◽  
pp. 369-374 ◽  
Author(s):  
K. Braun ◽  
S. Stern
Keyword(s):  
Pulmonary Artery ◽  
Blood Pressure Response ◽  
Pressor Response ◽  
Femoral Vein ◽  
Venous Pressure ◽  
Systemic Blood Pressure ◽  
Systemic Circulation ◽  
Ascending Aorta ◽  
Pulmonary Arterial

Large doses of serotonin (200 µg/ kg) in the anesthetized open-chest dog, administered into the femoral vein, right heart, pulmonary artery, left heart, ascending aorta or common carotid arteries, caused a marked pressor response in the systemic circulation. The latent period became shorter with the shift of the site of the injection toward the ascending aorta. After injection into the descending aorta a "double peak" pressor response was obtained. These observations, together with the demonstration of a much less pronounced pressor effect after elimination of the aortic and carotid chemoreceptors, indicate participation of chemoreceptor stimulation in the systemic pressor response. In the pulmonary artery the pressure rose markedly and consistently. A rise in the pulmonary venous pressure without any significant change in the left atrial pressure was observed, indicating pulmonary venous constriction. Chemoreceptor stimulation was shown to play a part also in the rise of both the pulmonary arterial and pulmonary venous pressures.

Effect of inhibition of NO synthase on vascular reactivity in a rat model of hyperdynamic sepsis

1994 ◽  
Vol 267 (4) ◽  
pp. H1377-H1382 ◽  
Author(s):  
G. A. Fox ◽  
N. A. Paterson ◽  
D. G. McCormack
Keyword(s):  
Vascular Reactivity ◽  
Blood Pressure Response ◽  
Pressor Response ◽  
Cecal Ligation ◽  
Systemic Blood Pressure ◽  
Systemic Circulation ◽  
No Synthase ◽  
Sprague Dawley ◽  
Significant Augmentation ◽  
Synthase Inhibitor

To evaluate the role of nitric oxide (NO) in the attenuated vascular reactivity observed in sepsis, we utilized the specific NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Male Sprague-Dawley rats (n = 16) were randomized to either sepsis induced by cecal ligation and perforation (CLP; n = 8) or sham procedure (Sham; n = 8). Vascular reactivity was assessed by measuring the pulmonary pressor response to hypoxia (HPV) (fractional inspired O2 concentration = 0.08) and the pulmonary and systemic pressor response to an intravenous infusion of phenylephrine (1.5-6.0 micrograms.kg-1.min-1). Twenty-four hours after surgery, CLP animals had significantly attenuated HPV compared with Sham animals. In response to hypoxia the change in total pulmonary vascular resistance during hypoxia was 0.008 +/- 0.004 and 0.021 +/- 0.006 mmHg.min-ml-1 in CLP and Sham animals, respectively (P < 0.05). The pulmonary and systemic blood pressure response to phenylephrine was also attenuated in CLP compared with Sham animals. After L-NAME infusion (15 mg/kg), there was a significant augmentation of the HPV response in Sham animals. In contrast, the HPV response in CLP animals was unchanged after L-NAME. The attenuated pressor response to phenylephrine in neither the pulmonary nor the systemic circulation was changed after the administration of L-NAME. These data suggest that in rats, excess NO is not an important mediator of the attenuated vascular reactivity observed in sepsis.

ID: 123: ROLE OF MICRORNA-1 IN REGULATING PULMONARY VASCULAR REMODELING IN PULMONARY ARTERIAL HYPERTENSION

2016 ◽  
Vol 64 (4) ◽  
pp. 969.1-969 ◽  
Author(s):  
JR Sysol ◽  
J Chen ◽  
S Singla ◽  
V Natarajan ◽  
RF Machado ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Vascular Remodeling ◽  
Luciferase Reporter ◽  
Pulmonary Vascular Remodeling ◽  
Pulmonary Arterial ◽  
Pulmonary Artery Smooth Muscle

RationalePulmonary arterial hypertension (PAH) is a severe, progressive disease characterized by increased pulmonary arterial pressure and resistance due in part to uncontrolled vascular remodeling. The mechanisms contributing to vascular remodeling in PAH are poorly understood and involve rampant pulmonary artery smooth muscle cell (PASMC) proliferation. We recently demonstrated the important role of sphingosine kinase 1 (SphK1), a lipid kinase producing pro-proliferative sphingosine-1-phosphate (S1P), in the development of pulmonary vascular remodeling in PAH. However, the regulatory processes involved in upregulation of SphK1 in this disease are unknown.ObjectiveIn this study, we aimed to identify novel molecular mechanisms governing the regulation of SphK1 expression, with a focus on microRNA (miR). Using both in vitro studies in pulmonary artery smooth muscle cells (PASMCs) and an in vivo mouse model of experimental hypoxia-mediated pulmonary hypertension (HPH), we explored the role of miR in controlling SphK1 expression in the development of pulmonary vascular remodeling.Methods and ResultsIn silico analysis identified hsa-miR-1-3p (miR-1) as a candidate targeting SphK1. We demonstrate miR-1 is down-regulated by hypoxia in human PASMCs and in lung tissues of mice with HPH, coinciding with upregulation of SphK1 expression. PASMCs isolated from patients with PAH had significantly reduced expression of miR-1. Transfection of human PASMCs with miR-1 mimics significantly attenuated activity of a SphK1-3'-UTR luciferase reporter construct and SphK1 protein expression. miR-1 overexpression in human PASMCs also inhibited proliferation and migration under normoxic and hypoxic conditions, both important in pathogenic vascular remodeling in PAH. Finally, we demonstrated that intravenous administration of miR-1 mimics prevents the development of experimental HPH in mice and attenuates induction of SphK1 in PASMCs.ConclusionThese data demonstrate that miR-1 expression in reduced in PASMCs from PAH patients, is modulated by hypoxia, and regulates the expression of SphK1. Key phenotypic aspects of vascular remodeling are influenced by miR-1 and its overexpression can prevent the development of HPH in mice. These studies further our understanding of the mechanisms underlying pathogenic pulmonary vascular remodeling in PAH and could lead to novel therapeutic targets.Supported by grants NIH/NHLBI R01 HL127342 and R01 HL111656 to RFM, NIH/NHLBI P01 HL98050 and R01 HL127342 to VN, American Heart Association Predoctoral Fellowship (15PRE2190004) to JRS, and NIH/NLHBI NRSA F30 Fellowship (FHL128034A) to JRS.

Effect of hypoxia on pulmonary artery pressure of dogs

1964 ◽  
Vol 207 (6) ◽  
pp. 1314-1318 ◽  
Author(s):  
Benson R. Wilcox ◽  
W. Gerald Austen ◽  
Harvey W. Bender
Keyword(s):  
Pulmonary Artery ◽  
Arterial Pressure ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Arterial Pressure ◽  
Venous Pressure ◽  
Artery Pressure ◽  
Pulmonary Vasoconstriction ◽  
Systemic Hypoxia ◽  
Pump Output ◽  
Pulmonary Arterial

The mechanism by which the pulmonary artery pressure rises in response to hypoxia has never been clearly demonstrated. This problem was reinvestigated in experiments utilizing separate pulmonary and systemic perfusion systems. These vascular beds were perfused in such a fashion that a change in pulmonary artery pressure could only result from changes in vasomotor tone. Alveolar-pulmonary vein hypoxia was usually associated with a slight fall in pulmonary artery pressure. Systemic hypoxia resulted in elevation of pulmonary arterial pressure in 10 of the 12 animals tested with a constant-flow and constant-pulmonary venous pressure. In addition, all animals with systemic desaturation showed an increased venous return. When the "cardiac output" (pump output) was increased to match this return, the elevation in pulmonary artery pressure increased. It was concluded that the pulmonary arterial pressure elevation seen with hypoxia is the result of active pulmonary vasoconstriction coupled with an increased pulmonary blood flow.

Sex Differences in Right Ventricular-Vascular Coupling and Pulmonary Artery Impedance in Response to Chronic Hypoxia and Recovery

2012 ◽  
Author(s):  
Aiping Liu ◽  
Lian Tian ◽  
Diana M. Tabima ◽  
Naomi C. Chesler
Keyword(s):  
Pulmonary Artery ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Pulmonary Artery Hypertension ◽  
Vascular Impedance ◽  
Female Predominance ◽  
Collagen Accumulation ◽  
Dominant Disease ◽  
Pulmonary Arterial

Pulmonary artery hypertension (PAH) is a female dominant disease (the female-to-male ratio is 4:1), characterized by small distal pulmonary arterial narrowing and large proximal arterial stiffening, which increase right ventricle (RV) afterload and ultimately lead to RV failure [1,2]. Our recent studies have shown that collagen accumulation induced by chronic hypoxia increases the stiffness of the large extralobar pulmonary arteries (PAs) [3], and affects pulmonary vascular impedance (PVZ) [4]. The role of collagen in the female predominance in developing PAH has not been explored to date.

Prevalence of pulmonary hypertension in adults after atrial switch and role of ventricular filling pressures

Heart ◽  
2020 ◽  
pp. heartjnl-2020-317111
Author(s):  
William R Miranda ◽  
C Charles Jain ◽  
Heidi M Connolly ◽  
Hilary M DuBrock ◽  
Frank Cetta ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Diastolic Pressure ◽  
Atrioventricular Valve Regurgitation ◽  
Switch Operation ◽  
Atrial Switch ◽  
Pulmonary Arterial ◽  
Atrial Switch Operation ◽  
Ventricular Filling ◽  
Wedge Pressure

ObjectiveTo assess the prevalence of elevated systemic right ventricular (sRV) end-diastolic pressure and pulmonary arterial hypertension in adults with transposition of the great arteries (TGA) who have undergone atrial switch operation.MethodsForty-two adults (aged ≥18 years) with complete TGA and atrial switch palliation undergoing cardiac catheterisation between 2004 and 2018 at Mayo Clinic, MN, were identified. Clinical, echocardiographic and invasive haemodynamic data were abstracted from the medical charts and procedure logs.ResultsMean age was 37.6±7.9 years; 28 were male (67%). The Mustard operation was performed in 91% of individuals. Mean estimated sRV ejection fraction by echocardiography was 33.3%±10.9% and ≥moderate tricuspid (systemic atrioventricular valve) regurgitation was present in 15 patients (36%). Mean sRV end-diastolic pressure was 13.2±5.4 mm Hg. An sRV end-diastolic pressure >15 mm Hg was present in 35% of individuals whereas a pulmonary artery wedge pressure (PAWP) >15 mm Hg was seen in 59%. Mean pulmonary artery pressure ≥25 mm Hg was seen in 47.5% of patients with PAWP being >15 mm Hg in all but one patient.ConclusionIn adults after atrial switch, elevated sRV end-diastolic pressure was present in only one-third of patients whereas increased PAWP was seen in almost 60%. These findings are most likely related to a combination of decreased pulmonary atrial (functional left atrium) compliance and, in a subset of patients, pulmonary venous baffle obstruction. Elevation in pulmonary pressures was highly prevalent with concomitant elevation in PAWP being present in essentially all patients.

Treatment with 5-HT potentiates development of pulmonary hypertension in chronically hypoxic rats

1997 ◽  
Vol 272 (3) ◽  
pp. H1173-H1181 ◽  
Author(s):  
S. Eddahibi ◽  
B. Raffestin ◽  
I. Pham ◽  
J. M. Launay ◽  
P. Aegerter ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Ventricular Hypertrophy ◽  
Potential Role ◽  
Pressor Response ◽  
Acute Hypoxia ◽  
Synthesis Inhibitor ◽  
Pulmonary Arterial ◽  
Isolated Lungs ◽  
Dose Dependent

The aim of this study was to investigate the potential role of 5-hydroxytryptamine (5-HT) on development of pulmonary hypertension during chronic exposure to mild (15% O2) and severe (10% O2) hypoxia. In isolated lungs from normoxic rats preconstricted with U-46619, 5-HT (10(-12)-10(-8) M) induced dose-dependent vasodilation (n = 6), which was suppressed by the NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME, 10(-4) M, n = 5) and reduced by the 5-HT3-receptor antagonist MDL-7222 (10(-5) M, n = 6). The vasoconstriction that was observed with higher concentrations of 5-HT (10(-7)-10(-4) M) was inhibited by ketanserin (10(-5) M) and methiothepin (10(-5) M, n = 6 each). The vasodilator response to 5-HT was suppressed in lungs from rats exposed to 10% O2 but not 15% O2 (n = 6 each). In conscious rats, intravenous administration of 5-HT potentiated the pulmonary pressor response to acute hypoxia (10% O2, n = 5), an effect that remained unchanged after pretreatment with a 5-HT1 and a 5-HT2 antagonist (n = 4) but was attenuated after treatment with the cyclooxygenase inhibitor meclofenamate (n = 4). Treatment with 5-HT (5 nmol/h i.v. by osmotic pumps) for 2 wk in rats simultaneously exposed to 10% O2 increased pulmonary arterial pressure, right ventricular hypertrophy, and muscularization of pulmonary vessels in comparison with their hypoxic controls (n = 12 each). No changes occurred in 15% O2 hypoxic rats (n = 12 each). The present findings show that 5-HT potentiates development of pulmonary hypertension in rats exposed to chronic hypoxia.

Improved techniques for cardiovascular monitoring in rats as applied during endotoxemia

1988 ◽  
Vol 254 (1) ◽  
pp. H181-H186
Author(s):  
B. Biber ◽  
C. F. Schaefer ◽  
M. J. Smolik ◽  
M. R. Lerner ◽  
D. J. Brackett ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Vascular Resistance ◽  
Venous Pressure ◽  
Systemic Blood Pressure ◽  
Systemic Arterial Pressure ◽  
New Combination ◽  
Conscious Rat ◽  
Injection Model ◽  
Pulmonary Arterial ◽  
Wedge Pressure

We describe a new combination of techniques for measurements of systemic blood pressure, central venous pressure, pulmonary arterial (PA) pressure, PA wedge pressure, and cardiac output in the rat. Application of the method to the conscious rat in a septic shock (Escherichia coli endotoxin iv injection) model demonstrated a response pattern of decreased cardiac output and stroke volume, increased total peripheral vascular resistance and heart rate, and transiently decreased systemic arterial pressure. In the pulmonary circulation, a very brief hypertension and a sustained increase in pulmonary vascular resistance were observed, but changes in PA wedge pressure were small. The soft PA catheter (0.3 mm ID, 0.6 mm OD) had no undue effects on cardiovascular function. We suggest that this combined technique could be useful for many cardiovascular studies in the rat, not only as related to shock research.

scholarly journals Pathobiology of pulmonary artery hypertension: role of long non-coding RNAs

2020 ◽  
Vol 116 (12) ◽  
pp. 1937-1947 ◽  
Author(s):  
Kashif Rafiq Zahid ◽  
Umar Raza ◽  
Jidong Chen ◽  
Usha J Raj ◽  
Deming Gou
Keyword(s):  
Pulmonary Artery ◽  
Right Ventricular Dysfunction ◽  
Pulmonary Artery Hypertension ◽  
Endothelial Cell Proliferation ◽  
Vascular Remodelling ◽  
Mesenchymal Transition ◽  
Pulmonary Arterial ◽  
Non Coding Rnas

Abstract Pulmonary arterial hypertension (PAH) is a disease with complex pathobiology, significant morbidity and mortality, and remains without a cure. It is characterized by vascular remodelling associated with uncontrolled proliferation of pulmonary artery smooth muscle cells, endothelial cell proliferation and dysfunction, and endothelial-to-mesenchymal transition, leading to narrowing of the vascular lumen, increased vascular resistance and pulmonary arterial pressure, which inevitably results in right heart failure and death. There are multiple molecules and signalling pathways that are involved in the vascular remodelling, including non-coding RNAs, i.e. microRNAs and long non-coding RNAs (lncRNAs). It is only in recent years that the role of lncRNAs in the pathobiology of pulmonary vascular remodelling and right ventricular dysfunction is being vigorously investigated. In this review, we have summarized the current state of knowledge about the role of lncRNAs as key drivers and gatekeepers in regulating major cellular and molecular trafficking involved in the pathogenesis of PAH. In addition, we have discussed the limitations and challenges in translating lncRNA research in vivo and in therapeutic applications of lncRNAs in PAH.

Understanding the Molecular Origins of Pulmonary Hypertension: Role of MicroRNAs

2012 ◽  
Vol 11 (3) ◽  
pp. 132-132
Author(s):  
Sebastien Bonnet
Keyword(s):  
Pulmonary Artery ◽  
Vascular Remodeling ◽  
Premature Death ◽  
Right Heart Failure ◽  
Pulmonary Vasculature ◽  
Inflammatory Processes ◽  
Pulmonary Arterial ◽  
Pulmonary Artery Smooth Muscle ◽  
Pulmonary Artery Endothelial Cell

Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature, defined by an elevated pulmonary vascular resistance, leading to right heart failure and premature death. The cause remains unknown and available treatments are limited. PAH is characterized by enhanced pulmonary artery smooth muscle cell (PASMC) and pulmonary artery endothelial cell (PAEC) proliferation and suppressed apoptosis within the pulmonary artery wall. It has been shown that this phenotype is associated with mitochondrial hyperpolarization and enhanced glycolysis over glucose oxidation (Warburg effect), which are sustained over time by the activation of the transcription factors HIF-1 and NFAT. Nonetheless, the mechanisms accounting for these abnormalities remain unknown. A common feature to all vascular remodeling processes is that in early stages of the disease, a significant increase in oxidative stress and inflammatory processes are observed, causing irreversible DNA damage and cell death.

Sign in / Sign up

Export Citation Format

Share Document