Cultured smooth muscle approach in the study of hypertension

1992 ◽  
Vol 70 (4) ◽  
pp. 573-579 ◽  
Author(s):  
Stephen C. Pang ◽  
Shannon L. Venance
Keyword(s):  
Cell Culture ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Spontaneously Hypertensive Rat ◽  
Marked Change ◽  
Culture Technique ◽  
Mesenteric Arteries ◽  
Experimental Hypertension ◽  
In Vitro Techniques

The systemic vasculature is known to undergo marked change in both human and experimental hypertension. The in vitro study of individual cellular components from the blood vessel wall and the regulation of their intracellular biochemical processes will aid in developing an understanding of the pathogenesis of hypertension. Vascular smooth muscle cells derived from the aorta and mesenteric arteries of normotensive and hypertensive rats can be successfully maintained in culture, providing a system free of confounding variables such as blood pressure. To assist in fully understanding the pathophysiology of hypertension, this cell culture model can be used to examine interactions between receptor and ligand, the transduction of an associated signal, characterization of subsequent intracellular responses and ultimately, quantification of a physiological and functional consequence of these events, for example, proliferation. The application of in vitro techniques to hypertension research will continue to contribute new knowledge to increase our understanding of the mechanisms behind the hypertensive disease process.Key words: experimental hypertension, spontaneously hypertensive rat, vascular smooth muscle, aorta, mesenteric arteries, cell culture technique.

In Vitro Vascular Cell Culture Systems – Vascular Smooth Muscle

2010 ◽  
pp. 69-96 ◽  
Author(s):  
K.A. Martin ◽  
E.M. Rzucidlo ◽  
M. Ding ◽  
B.L. Merenick ◽  
Z. Kasza ◽  
...  
Keyword(s):  
Cell Culture ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular Cell ◽  
Culture Systems ◽  
Cell Culture Systems

Effects of chronic portal hypertension on agonist-induced actin polymerization in small mesenteric arteries

2006 ◽  
Vol 290 (5) ◽  
pp. H1915-H1921 ◽  
Author(s):  
Xuesong Chen ◽  
Kristin Pavlish ◽  
Hai-Ying Zhang ◽  
Joseph N. Benoit
Keyword(s):  
Smooth Muscle ◽  
Portal Hypertension ◽  
Vascular Smooth Muscle ◽  
Actin Polymerization ◽  
Smooth Muscle Contraction ◽  
Isometric Tension ◽  
Mesenteric Arteries ◽  
Dynamic Regulation ◽  
Force Development

The ability of arterial smooth muscle to respond to vasoconstrictor stimuli is reduced in chronic portal hypertension (PHT). Additional evidence supports the existence of a postreceptor defect in vascular smooth muscle excitation contraction coupling. However, the nature of this defect is unclear. Recent studies have shown that vasoconstrictor stimuli induce actin polymerization in smooth muscle and that the associated increase in F-actin is necessary for force development. In the present study we have tested the hypothesis that impaired actin polymerization contributes to reduced vasoconstrictor function in small mesenteric arteries derived from rats with chronic prehepatic PHT. In vitro studies were conducted on small mesenteric artery vessel rings isolated from normal and PHT rats. Isometric tension responses to incremental concentrations of phenylephrine were significantly reduced in PHT arteries. The ability to polymerize actin in portal hypertensive mesenteric arteries stimulated by phenylephrine was attenuated compared with control. Inhibition of cAMP-dependent protein kinase (PKA) restored agonist-induced actin polymerization of arteries from PHT rats to normal levels. Depolymerization of actin in arteries from normal rats reduced maximal contractile force but not myosin phosphorylation, suggesting a key role for the dynamic regulation of actin polymerization in the maintenance of vascular smooth muscle contraction. We conclude that reductions in agonist-induced maximal force development of PHT vascular smooth muscle is due, in part, to impaired actin polymerization, and prolonged PKA activation may underlie these changes.

scholarly journals Vascular smooth muscle desensitization in rabbit epigastric and mesenteric arteries during hemorrhagic shock

2016 ◽  
Vol 311 (1) ◽  
pp. H157-H167 ◽  
Author(s):  
P. H. Ratz ◽  
A. S. Miner ◽  
Y. Huang ◽  
C. A. Smith ◽  
R. W. Barbee
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Mechanical Analysis ◽  
Mesenteric Arteries ◽  
Signaling Systems ◽  
Epigastric Artery ◽  
Artery Segment ◽  
Vascular Hyporeactivity

The decompensatory phase of hemorrhage (shock) is caused by a poorly defined phenomenon termed vascular hyporeactivity (VHR). VHR may reflect an acute in vivo imbalance in levels of contractile and relaxant stimuli favoring net vascular smooth muscle (VSM) relaxation. Alternatively, VHR may be caused by intrinsic VSM desensitization of contraction resulting from prior exposure to high levels of stimuli that temporarily adjusts cell signaling systems. Net relaxation, but not desensitization, would be expected to resolve rapidly in an artery segment removed from the in vivo shock environment and examined in vitro in a fresh solution. Our aim was to 1) induce shock in rabbits and apply an in vitro mechanical analysis on muscular arteries isolated pre- and postshock to determine whether VHR involves intrinsic VSM desensitization, and 2) identify whether net VSM relaxation induced by nitric oxide and cyclic nucleotide-dependent protein kinase activation in vitro can be sustained for some time after relaxant stimulus washout. The potencies of phenylephrine- and histamine-induced contractions in in vitro epigastric artery removed from rabbits posthemorrhage were decreased by ∼0.3 log units compared with the control contralateral epigastric artery removed prehemorrhage. Moreover, a decrease in KCl-induced tonic, relative to phasic, tension of in vitro mesenteric artery correlated with the degree of shock severity as assessed by rates of lactate and K+ accumulation. VSM desensitization was also caused by tyramine in vivo and PE in vitro, but not by relaxant agents in vitro. Together, these results support the hypothesis that VHR during hemorrhagic decompensation involves contractile stimulus-induced long-lasting, intrinsic VSM desensitization.

A review of changes in vascular smooth muscle functions in hypertension: isolated tissue versus in vivo studies

1985 ◽  
Vol 63 (4) ◽  
pp. 355-365 ◽  
Author(s):  
C. R. Triggle ◽  
I. Laher
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Function ◽  
Spontaneously Hypertensive Rat ◽  
In Vivo Studies ◽  
Neuronal Uptake ◽  
Smooth Muscle Function

The role of altered vascular smooth muscle function in the etiology of essential hypertension has been extensively studied by a number of investigators. The results obtained from in vivo studies do not always correlate with results from in vitro studies and it is not always apparent whether the results reflect differences related to hypertension or to the genetic background of the animal model. In vitro and perfused vascular bed studies in our laboratory have utilized the spontaneously hypertensive rat (SHR), the normotensive Wistar Kyoto rat (WKY), genetically related crossbred rats (F1, F2, and BC1), and also Dahl salt-sensitive (DS) and salt-resistant (DR) rats. The role of altered smooth muscle function in relation to the development of the elevated blood pressure (BP) of the SHR or DS rat was studied and emphasis was placed on determining the role of altered neuronal uptake1 (U1) in hypertensives in masking elevated postsynaptic sensitivity to noradrenaline. In addition, the relationship between postsynaptic sensitivity to cations and BP was assessed. Such studies have indicated that alterations in postsynaptic sensitivity, U1 activity, and sensitivity to cations are not entirely consistent with the etiology of hypertension in the SHR and DS rat but may simply reflect genetic strain differences between the hypertensive and normotensive animals.

P4477Editing of myosin phosphatase as a novel approach for sensitization of vascular smooth muscle to vasodilators (NO/cGMP/ROS) and lowering of blood pressure in hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Fisher ◽  
J J Reho ◽  
M Meddeb ◽  
J Ursitti ◽  
M Htet
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
World Wide ◽  
Mesenteric Arteries ◽  
Smooth Muscle Relaxation ◽  
Myosin Phosphatase ◽  
Substantial Impact

Abstract Background Despite the many drugs for treatment of hypertension, it remains inadequately treated in >50% of patients and the number one contributor to cardiovascular mortality world-wide. Thus new targets and treatment strategies are badly needed. Myosin Phosphatase (MP) is a viable target: it is the primary effector of vascular smooth muscle relaxation and a critical mediator of signaling pathways regulating vessel tone. Purpose We are using complementary/ translatable approaches to test the hypothesis: editing of the Myosin Phosphatase Regulatory (Targeting) subunit (MYPT1), by shifting the expression of naturally occurring isoforms, will sensitize vascular smooth muscle to NO/cGMP/ROS mediated vasorelaxation and thereby lower BP in models of hypertension. A further goal is to determine mechanisms by which these signals activate MP thereby causing vasorelaxation. Methods LoxP sites were inserted in introns flanking alternative Exon24 (E24) of Mypt1. Mice were crossed with smMHCCreER mice and treated with Tamoxifen for smooth muscle specific deletion of E24 (SMcKO E24).Skipping E24 codes for a Mypt1 isoform that contains a C-terminal leucine zipper (LZ) motif required for cGMP-dependent protein kinase (cGK1) binding and NO/cGMP/ROS activation of MP. Second, we developed and tested guide RNAs for the purpose of AAV-CRISPR/CAS9 editing of Mypt1 E24 as a treatment for hypertension. Effect of editing is tested in otherwise normal mice and in the AngII sub-pressor model of hypertension. Results SMcKO E24 mice had mean BP that was 15+3 mmHg lower than control (n=5; p<0.05). Mesenteric arteries from these mice were significantly more sensitive to DEA/NO mediated relaxation (EC50: 2.1+0.5 nM vs 18.2+5.6 mM; n=5–6, p<0.05). Experiments testing response to AngII infusion are in progress and will be presented at the meeting. Preliminary biochemical assays support a 2-pool model, in which NO/cGMP/ROS activates the LZ+ pool, while contractile agonists inhibit the LZ- pool of MP, in the control of BP/ blood flow. We have generated a number of AAV Crispr/Cas9 gRNAs and validated their efficacy of editing of Mypt1 E24 in vitro. Experiments are in progress to test their efficacy and effect on BP in vivo. Conclusion These studies support that editing of Mypt1 E24 could be a novel strategy for vasodilator sensitization and effective lowering of blood pressure in humans with hypertension, thereby having a substantial impact on CV mortality world-wide. Acknowledgement/Funding NIH

NHE-1 Protein in Vascular Smooth Muscle and Lymphocytes From the Spontaneously Hypertensive Rat

Hypertension ◽  
1997 ◽  
Vol 30 (4) ◽  
pp. 880-885 ◽  
Author(s):  
Michael S. LaPointe ◽  
Minghao Ye ◽  
Robert Bacallao ◽  
Daniel Batlle
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat
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