Cardiovascular effects and cardiopulmonary plasma gradients following intravenous infusion of neuropeptide Y in humans: negative dromotropic effect on atrioventricular node conduction

2002 ◽  
Vol 103 (6) ◽  
pp. 535-542 ◽  
Author(s):  
Bengt ULLMAN ◽  
John PERNOW ◽  
Jan M. LUNDBERG ◽  
Hans ÅSTRÖM ◽  
Lennart BERGFELDT
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Neuropeptide Y ◽  
Bolus Injection ◽  
Plasma Concentrations ◽  
Systemic Blood Pressure ◽  
Cardiac Conduction ◽  
Systemic Blood ◽  
Av Node

Neuropeptide Y (NPY) is co-released with noradrenaline from sympathetic nerves, has a strong vasoconstrictive action, and causes an attenuation of parasympathetic action in animal experiments. The plasma level of NPY is greatly elevated in patients with congestive heart failure, but the clinical relevance of this finding is unclear. Central haemodynamic effects, cardiac conduction system electrophysiology and coronary sinus blood flow were therefore studied in two sets of experiments, each carried out on seven healthy men. In the first series, NPY was given intravenously at doses of 3, 10 and 30pmolμmin-1μkg-1, and in the second it was given as a bolus injection of 90, 200 or 900pmol/kg, which resulted in plasma concentrations similar to those seen in heart failure patients. During continuous infusion of NPY, systemic blood pressure increased slightly, but myocardial perfusion, cardiac output, pulmonary arterial pressure, cardiac conduction intervals and atrioventricular (AV) node functional measures remained unchanged. In contrast, the bolus injection of NPY evoked prolongation and block (in four out of seven subjects) of AV node conduction, but did not affect haemodynamic variables, apart from a minor increase in systemic blood pressure. Impaired AV node conduction is a novel observation, which might reflect a baroreceptor-mediated vagal reflex, or–more likely–an NPY-induced direct negative dromotropic effect, caused by a reduction of the L-type calcium current as observed in vitro, or a combination of the two.

Methylprednisolone on circulating eicosanoids and vasomotor tone after endotoxin

1986 ◽  
Vol 61 (1) ◽  
pp. 185-191 ◽  
Author(s):  
C. A. Hales ◽  
R. D. Brandstetter ◽  
C. F. Neely ◽  
M. B. Peterson ◽  
D. Kong ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Resistance ◽  
Systemic Blood Pressure ◽  
Physiological Effect ◽  
High Dose ◽  
Systemic Blood ◽  
Eicosanoid Production ◽  
Circulating Levels

Acute pulmonary and systemic vasomotor changes induced by endotoxin in dogs have been related, at least in part, to the production of eicosanoids such as the vasoconstrictor thromboxane and the vasodilator prostacyclin. Steroids in high doses, in vitro, inhibit activation of phospholipase A2 and prevent fatty acid release from cell membranes to enter the arachidonic acid cascade. We, therefore, administered methylprednisolone (40 mg/kg) to dogs to see if eicosanoid production and the ensuing vasomotor changes could be prevented after administration of 150 micrograms/kg of endotoxin. The stable metabolites of thromboxane B2 (TxB2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were measured by radioimmunoassay. Methylprednisolone by itself did not alter circulating eicosanoids but when given 2.5 h before endotoxin not only failed to inhibit endotoxin-induced eicosanoid production but actually resulted in higher circulating levels of 6-keto-PGF1 alpha (P less than 0.05) compared with animals receiving endotoxin alone. Indomethacin prevented the steroid-enhanced concentrations of 6-keto-PGF1 alpha after endotoxin and prevented the greater fall (P less than 0.05) in systemic blood pressure and systemic vascular resistance with steroid plus endotoxin than occurred with endotoxin alone. Administration of methylprednisolone immediately before endotoxin resulted in enhanced levels (P less than 0.05) of both TxB2 and 6-keto-PGF1 alpha but with a fall in systemic blood pressure and vascular resistance similar to the animals pretreated by 2.5 h. In contrast to the early steroid group in which all of the hypotensive effect was due to eicosanoids, in the latter group steroids had an additional nonspecific effect. Thus, in vivo, high-dose steroids did not prevent endotoxin-induced increases in eicosanoids but actually increased circulating levels of TxB2 and 6-keto-PGF1 alpha with a physiological effect favoring vasodilation.

Abstract 066: The Undescribed Protein Caskin2 Is a Novel Regulator of eNOS Phosphorylation and Systemic Blood Pressure

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Sarah B Mueller ◽  
Susan B Gurley ◽  
Christopher D Kontos
Keyword(s):  
Blood Pressure ◽  
Molecular Mechanisms ◽  
Systemic Blood Pressure ◽  
Regulatory Subunit ◽  
Systemic Blood ◽  
Homologous Expression ◽  
Ongoing Work ◽  
Inducing Factors

Disruptions in the function of the quiescent endothelial cells (ECs) that line mature vessels can both result in and contribute to the progression of numerous cardiovascular diseases including hypertension, atherosclerosis, and disorders of vascular permeability. Despite recent attention, the signaling pathways that are active in quiescent ECs remain poorly characterized relative to those that regulate EC activation. In an effort to provide mechanistic insight into these pathways, we have characterized the previously undescribed protein Caskin2, which we hypothesize is a novel regulator of EC quiescence. Caskin2 is expressed in ECs throughout the vasculature, including the aorta, coronary arteries, and renal glomeruli. In vitro, Caskin2 promotes a quiescent EC phenotype characterized by decreased proliferation and increased resistance to apoptosis-inducing factors. Caskin2 knockout mice are viable and fertile. However, preliminary radiotelemetry measurements indicate that Caskin2 knockout (KO) mice have mildly elevated systemic blood pressure (BP). Compared to wild type (WT) littermates (n=8), Caskin2 KO mice (n=7) had increased mean arterial pressure (119+/-1 vs. 113+/-1, p=0.012), systolic BP (138+/-2 vs. 132+/-2, p=0.023), and diastolic BP (99+/-1 vs. 93+/-1, p=0.014) at baseline. To explore the molecular mechanisms of Caskin2’s effects, we used mass spectrometry to identify interacting proteins. Among the 67 proteins identified were the Ser/Thr phosphatase protein phosphatase 1 (PP1) and eNOS. Using standard in vitro biochemical techniques, we demonstrated that Caskin2 acts as a PP1 regulatory subunit. Interestingly, homologous expression of Caskin2 in vitro resulted in a marked increase in phosphorylation of eNOS on S1177, which is known to promote eNOS activity, and a decrease in phosphorylation on T495, which is associated with eNOS inhibition. Finally, PP1 has been shown to dephosphorylate eNOS T495 in vitro, suggesting a molecular mechanism for our in vivo findings. Ongoing work aims to determine if the interaction of Caskin2 and PP1 is required for the Caskin2-induced increase in activating phosphorylation of eNOS and to characterize the physiological mechanisms responsible for Caskin2’s effects on BP in more detail.

NaCl modulates captopril effects on glomerular prostaglandin synthesis and glomerular filtration

1990 ◽  
Vol 258 (2) ◽  
pp. F382-F387
Author(s):  
M. Rathaus ◽  
E. Podjarny ◽  
A. Pomeranz ◽  
J. Bernheim
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Specific Effect ◽  
Systemic Blood Pressure ◽  
Prostaglandin Synthesis ◽  
Volume Loading ◽  
Systemic Blood

Captopril stimulates glomerular prostaglandin (PG) synthesis and increases glomerular filtration rate (GFR) in Na-repleted rats, whereas, in Na-depleted rats, it fails to stimulate PG synthesis and decreases GFR. In the present work the influence of chronic and acute NaCl loading on PG synthesis and renal function was studied in Na-depleted rats receiving captopril (LNC rats). Glomerular PGE2 and 6-keto-PGF1 alpha were not increased in LNC rats and were significantly lower than in Na-depleted rats (LN). Na repletion, while continuing captopril, increased PG synthesis above control levels. Addition of captopril in vitro to the incubation medium stimulated PGE2 synthesis in glomeruli of control rats, whereas it depressed it in LN rats. Acute loading with NaCl in LNC rats increased inulin and PAH clearances to values significantly greater than in control rats and similar to those of normal rats receiving captopril. Comparable volume loading with isotonic mannitol or 3% albumin increased inulin and PAH clearances only to control values. The specific effect of NaCl in acute loading was prevented by cyclooxygenase inhibition and was not mediated by increased systemic blood pressure. The results provide evidence that the effects of captopril on glomerular PG synthesis and renal function depend on the state of Na balance.

scholarly journals Oh, the places you'll go! My many colored serotonin (apologies to Dr. Seuss)

2016 ◽  
Vol 311 (5) ◽  
pp. H1225-H1233 ◽  
Author(s):  
Stephanie W. Watts
Keyword(s):  
Blood Pressure ◽  
Systemic Blood Pressure ◽  
Systemic Blood ◽  
Chronic Infusion ◽  
History Of ◽  
Normotensive Subjects ◽  
Arterial Tone ◽  
Venous Vasculature

Serotonin [5-hydroxytryptamine (5-HT)] has a truly fascinating history in the cardiovascular world. Discovered in the blood, 5-HT has long been appropriately regarded as a vasoconstrictor. A multitude of in vitro studies of isolated vessels support that addition of 5-HT causes vascular contraction. In only a few cases was 5-HT a vasodilator. Moreover, the potency and threshold of 5-HT causing contraction is increased in arteries from hypertensive vs. normotensive subjects, both animal and human. As such, we and others have hypothesized that 5-HT would contribute to hypertension by elevating arterial tone. In stark contrast to these decades of findings, we observed that a chronic infusion of 5-HT into conscious rats caused a reduction in blood pressure and nearly normalized blood pressure of experimentally hypertensive rats. Going back to the early work of Irvine Page, one of the scientists who discovered 5-HT, reveals an early recognized but never understood ability of 5-HT to reduce systemic blood pressure. Our laboratory, in collaboration with colleagues around the world, has dedicated itself to understanding the mechanisms of 5-HT-induced reduction in blood pressure. This manuscript takes you through a brief history of the discovery of 5-HT, in vitro serotonergic pharmacology of blood vessels, in vivo work with 5-HT and our studies that suggests the venous vasculature, potentially in combination with small arterioles, may be important to the actions of 5-HT in reducing blood pressure. 5-HT has certainly ended up in a place I never expected it to go.

scholarly journals Hypoxia-induced small extracellular vesicle proteins regulate proinflammatory cytokines and systemic blood pressure in pregnant rats

2020 ◽  
Vol 134 (6) ◽  
pp. 593-607 ◽  
Author(s):  
Suchismita Dutta ◽  
Andrew Lai ◽  
Katherin Scholz-Romero ◽  
Muhammad J. A. Shiddiky ◽  
Yusuke Yamauchi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
Oxygen Tension ◽  
Systemic Blood Pressure ◽  
Extravillous Trophoblast ◽  
Low Oxygen ◽  
Systemic Blood ◽  
Pregnant Rats ◽  
Differentially Abundant Proteins

Abstract Small extracellular vesicles (sEVs) released from the extravillous trophoblast (EVT) are known to regulate uterine spiral artery remodeling during early pregnancy. The bioactivity and release of these sEVs differ under differing oxygen tensions and in aberrant pregnancy conditions. Whether the placental cell-derived sEVs released from the hypoxic placenta contribute to the pathophysiology of preeclampsia is not known. We hypothesize that, in response to low oxygen tension, the EVT packages a specific set of proteins in sEVs and that these released sEVs interact with endothelial cells to induce inflammation and increase maternal systemic blood pressure. Using a quantitative MS/MS approach, we identified 507 differentially abundant proteins within sEVs isolated from HTR-8/SVneo cells (a commonly used EVT model) cultured at 1% (hypoxia) compared with 8% (normoxia) oxygen. Among these differentially abundant proteins, 206 were up-regulated and 301 were down-regulated (P < 0.05), and they were mainly implicated in inflammation-related pathways. In vitro incubation of hypoxic sEVs with endothelial cells, significantly increased (P < 0.05) the release of GM-CSF, IL-6, IL-8, and VEGF, when compared with control (i.e. cells without sEVs) and normoxic sEVs. In vivo injection of hypoxic sEVs into pregnant rats significantly increased (P < 0.05) mean arterial pressure with increases in systolic and diastolic blood pressures. We propose that oxygen tension regulates the release and bioactivity of sEVs from EVT and that these sEVs regulate inflammation and maternal systemic blood pressure. This novel oxygen-responsive, sEVs signaling pathway, therefore, may contribute to the physiopathology of preeclampsia.

Nonselective ETA/ETB-receptor blockade increases systemic blood pressure of Bio 14.6 cardiomyopathic hamstersThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

2008 ◽  
Vol 86 (6) ◽  
pp. 394-401 ◽  
Author(s):  
Jean-Claude Honoré ◽  
Émilie Carrier ◽  
Marie-Hélène Fecteau ◽  
Carlos R. Tirapelli ◽  
Ghassan Bkaily ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Congestive Heart Failure ◽  
Systemic Blood Pressure ◽  
Left Ventricular ◽  
Receptor Blockade ◽  
Receptor Antagonists ◽  
Systemic Blood ◽  
Receptor Antagonism ◽  
Cardiomyopathic Hamsters

To examine the role of endothelin ETA and ETB receptors in congestive heart failure due to cardiomyopathy, the effect of chronic treatment with selective ETA- and ETB-receptor antagonists (atrasentan and A-192621, respectively), alone and in combination, was assessed on functional and biochemical parameters of 52-week-old Bio 14.6 cardiomyopathic hamsters. Compared with control animals, cardiomyopathic hamsters treated for 9 weeks with atrasentan showed no variation in MAP; however, selective ETB- and combined nonselective ETA- and ETB-receptor antagonists increased systemic blood pressure. After selective ETB-receptor blockade, plasma endothelin levels were augmented. Importantly, this increase was highly enhanced (more than 8-fold) by concomitant ETA-receptor antagonism. Furthermore, the left ventricle : body weight ratio of cardiomyopathic hamsters treated with A-192621, alone or in combination with atrasentan, was significantly increased. On the other hand, decreased left ventricular end-diastolic pressure was observed in cardiomyopathic hamsters after selective ETA- or combined nonselective ETA/ETB-receptor antagonism, while only selective ETA-receptor blockade reduced left ventricular endothelin levels. Our results suggest that, in congestive heart failure, ETB receptors are essential to limit circulating endothelin levels, which may argue for improved cardiac benefits after long-term treatment with highly selective ETA-receptor antagonists.

Decreasing systemic blood pressure impairs cerebral vascular reserves in patients with steno-occlusive cerebral vascular diseases: A repeated I-123 split dose spect study

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S404-S404
Author(s):  
Yasuyuki Kimura ◽  
Naohiko Oku ◽  
Katsufumi Kajimoto ◽  
Hiroki Kato ◽  
Makiko Tanaka ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Diseases ◽  
Systemic Blood Pressure ◽  
Systemic Blood ◽  
Split Dose ◽  
Cerebral Vascular

scholarly journals Pressure constrained mitral annular dysfunction determines severity of regurgitation in Barlow's disease – a 3D echocardiographic study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.A Dumont ◽  
R Persson ◽  
J.P Kvitting ◽  
R Lundblad ◽  
R Haaverstad ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Aortic Valve ◽  
Mitral Regurgitation ◽  
Surface Area ◽  
Systemic Blood Pressure ◽  
Funding Source ◽  
Healthy Controls ◽  
Systemic Blood ◽  
Barlow’S Disease ◽  
3D Echo

Abstract Background Barlow's disease provides both diagnostic and therapeutic challenges. The impact of systemic blood-pressure on severity of regurgitation is still unclear. Purpose We hypothesized that mitral annulus behaves passively with enlargement during ventricular systole, and secondly, we tested the hypothesis that severity of regurgitation correlates to systemic blood-pressure (BP) of the patient. Methods Ten patients with Barlow's disease were compared with 10 healthy controls. Brachial blood-pressure was measured according to guidelines. Transthoracic 3D echo was obtained from an apical view (38.6±8.2 frames per second). Data was analyzed using a holographic display. We measured commissure width (CW), septallateral length (SL) and mitral annular surface area throughout the cardiac cycle. Aortic flow ejection time was derived from continuous Doppler across the aortic valve. Timing of aortic valve closure was visually assessed by 3D echo. Onset and end of mitral regurgitation was derived from continuous wave Doppler of transmitral flow. Results Systolic BP in controls and patients were 122±5 and 133±12 mmHg, respectively (p<0.05). Enddiastolic volume was 87±7 ml/m2 (controls) and 100±14 ml/m2 (Barlow), p<0.02. Left ventricular EF in controls and patients were 59±5 and 62±5%, respectively, p=NS. Barlow patients had moderate or severe late systolic regurgitation with mean regurgitation volume of 51±18 ml. Annular surface area, CW and SL behaved passively with enlargement during ventricular systole (Figure 1). Peak systolic surface area, CW and SL in healthy controls and Barlow patients were 8.7±0.5 vs 20.7±3.2 cm2 (p<0.001), 30.1±1.5 vs 49.5±4.9 mm (p<0.001) and 30.9±1.5 vs 44.9±3.3 mm (p<0.001). Peak annular surface area and regurgitation volume in patients showed a positive correlation with systolic BP (y = 0.156x − 0.077, r=0.60 and y = 1.136x − 99.7, r=0.80, respectively). Conclusions We have demonstrated pressure constrained mitral annular dysfunction in Barlow's disease, indicating that systemic blood pressure may modify the severity of regurgitation. The study provides novel insights into mechanisms of mitral regurgitation and potential therapeutic actions in the future. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Grieg Foundation

PS 02-65 ASSOCIATION BETWEEN POSTPRANDIAL AND SLEEPING SYSTEMIC BLOOD PRESSURE CHANGES IN THE NON-DIABETIC ELDERLY

2016 ◽  
Vol 34 (Supplement 1) ◽  
pp. e121
Author(s):  
Fernando Garcia ◽  
Beatriz Fidale ◽  
Sebastião Ferreira-Filho
Keyword(s):  
Blood Pressure ◽  
Systemic Blood Pressure ◽  
Systemic Blood ◽  
Pressure Changes
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