5-HT in systemic hypertension: foe, friend or fantasy?

2005 ◽  
Vol 108 (5) ◽  
pp. 399-412 ◽  
Author(s):  
Stephanie W. WATTS
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Potential Role ◽  
Muscle Growth ◽  
Systemic Hypertension ◽  
Vascular Control ◽  
Arterial Contraction ◽  
Arterial Contractility ◽  
Cell Mitogen

Since its discovery by Erspamer in the 1930s and identification by Page in the 1950s, 5-HT (5-hydroxytryptamine; serotonin) has been an elusive candidate as a substance that plays a role in the disease of high blood pressure, also known as hypertension. In both animal and human hypertension, arterial contraction to 5-HT is profoundly enhanced. Additionally, 5-HT is a vascular smooth muscle cell mitogen. Because both increased arterial contractility and smooth muscle growth contribute to the disease of hypertension, it is logical to believe that 5-HT is a potential cause of disease, and thus a foe. However, decades of research have produced conflicting results as to the potential role of 5-HT in hypertension. This review will discuss historical findings which both support and refute the involvement of 5-HT in hypertension, and pose some new questions that may reveal novel ways for 5-HT to modify vascular control of blood pressure.

Role of vasoconstrictors in the systemic hypertension of rats acclimatized to hypoxia

1995 ◽  
Vol 79 (5) ◽  
pp. 1657-1667 ◽  
Author(s):  
Y. Moue ◽  
P. G. Smith ◽  
R. L. Clancy ◽  
N. C. Gonzalez
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Sodium Nitroprusside ◽  
Barometric Pressure ◽  
Systemic Hypertension ◽  
Ang Ii ◽  
Arterial Blood ◽  
Smooth Muscle Relaxant

Exposure to hypoxia (2–5 wk) results in systemic hypertension in rats and in humans. The possible mechanism(s) was investigated in rats acclimatized for 3 wk to barometric pressure of approximately 370 Torr (A) and in nonacclimatized littermates (NA) by administration of alpha-adrenergic [phentolamine (PHLM)], angiotensin II (ANG II), and arginine vasopressin (AVP V1) receptor antagonists. Both A and NA rats were studied in hypoxia (inspiratory O2 fraction = 0.10). Baseline mean arterial blood pressure (MABP) was higher in A than in NA rats: 126 +/- 4 vs. 101 +/- 2 mmHg (P < 0.05). Neither ANG II nor AVP V1 receptor antagonist influenced baseline MABP; however, both contributed to MABP recovery after PHLM. After simultaneous blockade of ANG II and AVP V1, PHLM lowered MABP by 65 +/- 2 and 45 +/- 3 mmHg in A and NA rats, respectively (P < 0.05). After combined blockade of the three systems, the smooth muscle relaxant sodium nitroprusside did not further modify MABP, which remained higher in A rats. It is concluded that 1) the hypertension in A rats is partly due to a higher alpha-adrenergic tone, 2) neither ANG II nor AVP contributes to the hypertension, but ANG II and AVP participate in MABP control after PHLM, 3) no other vasoconstrictor agents operate in either group, and 4) the higher MABP in A rats after sodium nitroprusside may reflect additional hypertensive mechanisms.

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.

Relationship between serum myostatin levels and carotid-femoral pulse wave velocity in healthy young male adolescents: the MACISTE study

2021 ◽  
Vol 130 (4) ◽  
pp. 987-992
Author(s):  
Giacomo Pucci ◽  
Stefano Ministrini ◽  
Elisa Nulli Migliola ◽  
Luisa Nunziangeli ◽  
Francesca Battista ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Pulse Wave ◽  
Early Stage ◽  
Muscle Growth ◽  
Young Male ◽  
Systemic Hypertension ◽  
Vascular Aging ◽  
Healthy Male ◽  
Male Adolescents

Serum myostatin, a proteic compound known to regulate skeletal muscle growth and production of extracellular matrix, is independently associated with increased aortic stiffness in healthy male adolescents. This result sheds lights on the potential novel role of myokines in the early development of systemic hypertension and early vascular aging, as well as on their inhibition as a hypothetical therapeutic strategy to counteract vascular aging at an early stage of physical development.

IL-4 and IL-13 upregulate arginase I expression by cAMP and JAK/STAT6 pathways in vascular smooth muscle cells

2000 ◽  
Vol 279 (1) ◽  
pp. C248-C256 ◽  
Author(s):  
Liu Hua Wei ◽  
Aaron T. Jacobs ◽  
Sidney M. Morris ◽  
Louis J. Ignarro
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Growth ◽  
Muscle Cells ◽  
Protein Levels ◽  
Ifn Γ ◽  
Arginase Ii ◽  
Arginase I

The objectives of this study were to determine whether rat aortic smooth muscle cells (RASMC) express arginase and to elucidate the possible mechanisms involved in the regulation of arginase expression. The results show that RASMC contain basal arginase I (AI) activity, which is significantly enhanced by stimulating the cells with either interleukin (IL)-4 or IL-13, but arginase II (AII) expression was not detected under any condition studied here. We further investigated the signal transduction pathways responsible for AI induction. AI mRNA and protein levels were enhanced by addition of forskolin (1 μM) and inhibited by H-89 (30 μM), suggesting positive regulation of AI by a protein kinase A pathway. Genistein (10 μg/ml) and sodium orthovanadate (Na3VO4; 10 μM) were used to investigate the role of tyrosine phosphorylation in the control of AI expression. Genistein inhibited, whereas Na3VO4enhanced the induction of AI by IL-4 or IL-13. Along with immunoprecipitation and immunoblot analyses, these data implicate the JAK/STAT6 pathway in AI regulation. Dexamethasone (Dex) and interferon (IFN)-γ were investigated for their effects on AI induction. Dex (1 μM) and IFN-γ (100 U/ml) alone had no effect on basal AI expression in RASMC, but both reduced AI induction by IL-4 and IL-13. In combination, Dex and IFN-γ abolished AI induction by IL-4 and IL-13. Finally, both IL-4 and IL-13 significantly increased RASMC DNA synthesis as monitored by [3H]thymidine incorporation, demonstrating that upregulation of AI is correlated with an increase in cell proliferation. Blockade of AI induction by IFN-γ, H-89, or genistein also blocked the increase in cell proliferation. These observations are consistent with the possibility that upregulation of AI might play an important role in the pathophysiology of vascular disorders characterized by excessive smooth muscle growth.

scholarly journals The Role of Uridine Adenosine Tetraphosphate in the Vascular System

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Rita C. Tostes ◽  
R. Clinton Webb
Keyword(s):  
Smooth Muscle ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Arterial Hypertension ◽  
Smooth Muscle Cells ◽  
Vascular Function ◽  
Purinergic Receptors ◽  
Potential Role ◽  
Vascular System

The endothelium plays a pivotal role in vascular homeostasis, and endothelial dysfunction is a major feature of cardiovascular diseases, such as arterial hypertension, atherosclerosis, and diabetes. Recently, uridine adenosine tetraphosphate (Up4A) has been identified as a novel and potent endothelium-derived contracting factor (EDCF). Up4A structurally contains both purine and pyrimidine moieties, which activate purinergic receptors. There is an accumulating body of evidence to show that Up4A modulates vascular function by actions on endothelial and smooth muscle cells. In this paper, we discuss the effects of Up4A on vascular function and a potential role for Up4A in cardiovascular diseases.

scholarly journals Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension

2011 ◽  
Vol 301 (2) ◽  
pp. H584-H591 ◽  
Author(s):  
Wei-Qi He ◽  
Yan-Ning Qiao ◽  
Cheng-Hai Zhang ◽  
Ya-Jing Peng ◽  
Chen Chen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Vascular Tone ◽  
Induced Hypertension ◽  
Basal Blood Pressure ◽  
Muscle Myosin

Vascular tone, an important determinant of systemic vascular resistance and thus blood pressure, is affected by vascular smooth muscle (VSM) contraction. Key signaling pathways for VSM contraction converge on phosphorylation of the regulatory light chain (RLC) of smooth muscle myosin. This phosphorylation is mediated by Ca2+/calmodulin-dependent myosin light chain kinase (MLCK) but Ca2+-independent kinases may also contribute, particularly in sustained contractions. Signaling through MLCK has been indirectly implicated in maintenance of basal blood pressure, whereas signaling through RhoA has been implicated in salt-induced hypertension. In this report, we analyzed mice with smooth muscle-specific knockout of MLCK. Mesenteric artery segments isolated from smooth muscle-specific MLCK knockout mice (MLCKSMKO) had a significantly reduced contractile response to KCl and vasoconstrictors. The kinase knockout also markedly reduced RLC phosphorylation and developed force. We suggest that MLCK and its phosphorylation of RLC are required for tonic VSM contraction. MLCKSMKO mice exhibit significantly lower basal blood pressure and weaker responses to vasopressors. The elevated blood pressure in salt-induced hypertension is reduced below normotensive levels after MLCK attenuation. These results suggest that MLCK is necessary for both physiological and pathological blood pressure. MLCKSMKO mice may be a useful model of vascular failure and hypotension.

The Potential Role of Catheter-Based Renal Sympathetic Denervation in Chronic and End-Stage Kidney Disease

2016 ◽  
Vol 21 (4) ◽  
pp. 344-352 ◽  
Author(s):  
Yusuke Sata ◽  
Markus P. Schlaich
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Kidney Disease ◽  
End Stage Renal Disease ◽  
Renal Denervation ◽  
Potential Role ◽  
Stage Renal Disease ◽  
End Stage ◽  
Renal Sympathetic

Sympathetic activation is a hallmark of chronic and end-stage renal disease and adversely affects cardiovascular prognosis. Hypertension is present in the vast majority of these patients and plays a key role in the progressive deterioration of renal function and the high rate of cardiovascular events in this patient cohort. Augmentation of renin release, tubular sodium reabsorption, and renal vascular resistance are direct consequences of efferent renal sympathetic nerve stimulation and the major components of neural regulation of renal function. Renal afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in blood pressure control via hypothalamic integration. Renal denervation of the kidney has been shown to reduce blood pressure in many experimental models of hypertension. Targeting the renal nerves directly may therefore be specifically useful in patients with chronic and end-stage renal disease. In this review, we will discuss the potential role of catheter-based renal denervation in patients with impaired kidney function and also reflect on the potential impact on other cardiovascular conditions commonly associated with chronic kidney disease such as heart failure and arrhythmias.

scholarly journals MicroRNA-143/-145 in Cardiovascular Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Wang Zhao ◽  
Shui-Ping Zhao ◽  
Yu-Hong Zhao
Keyword(s):  
Smooth Muscle ◽  
Cardiovascular Diseases ◽  
Vascular Smooth Muscle Cells ◽  
Essential Role ◽  
Recent Progress ◽  
Potential Role ◽  
Phenotypic Switching ◽  
Diagnostic Biomarkers ◽  
Potential Strategy

MicroRNAs (miRNAs) play an essential role in the onset and development of many cardiovascular diseases. Increasing evidence shows that miRNAs can be used as potential diagnostic biomarkers for cardiovascular diseases, and miRNA-based therapy may be a promising therapy for the treatment of cardiovascular diseases. The microRNA-143/-145 (miR-143/-145) cluster is essential for differentiation of vascular smooth muscle cells (VSMCs) and determines VSMC phenotypic switching. In this review, we summarize the recent progress in knowledge concerning the function of miR-143/-145 in the cardiovascular system and their role in cardiovascular diseases. We discuss the potential role of miR-143/-145 as valuable biomarkers for cardiovascular diseases and explore the potential strategy of targeting miR-143 and miR-145.

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