Systemic hemodynamic effects of endothelin in rats

1990 ◽  
Vol 258 (3) ◽  
pp. H787-H792 ◽  
Author(s):  
A. J. King ◽  
J. M. Pfeffer ◽  
M. A. Pfeffer ◽  
B. M. Brenner
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Early Phase ◽  
Late Phase ◽  
Peripheral Resistance ◽  
Resistance Index ◽  
Right Atrial ◽  
Ang Ii ◽  
Hemodynamic Effects ◽  
Systemic Hemodynamic

Endothelin type 1 (ET-1) is an endothelial cell-derived 21-amino acid peptide with potent contractile effects on isolated vascular smooth muscle. The systemic hemodynamic effects of bolus intravenous injections of ET-1 and angiotensin II (ANG II, 300 pmol) were examined in anesthetized male Munich-Wistar rats by measurements of mean arterial (AP) and right atrial (RAP) blood pressures and cardiac index (CI, electromagnetic flowmetry) over a 60-min period. ET-1 induced a biphasic pressure response: transient hypotension occurred in the early phase with all doses, followed by a more prolonged dose-dependent elevation of blood pressure in the late phase. Because CI was unchanged during the early phase, the hypotension resulted from systemic vasodilation. On the other hand, the marked rise in AP produced by 300 pmol of ET-1 in the late phase was associated with a significant fall in CI, and thus total peripheral resistance index (TPRI) increased profoundly. A fall in right atrial pressure and significant hemoconcentration were associated with this pronounced vasoconstrictor effect, suggesting that a contraction of plasma volume contributed to the reduction of CI. Additionally, stroke and minute work indexes and peak flow velocity became significantly reduced in the late phase for the 300-pmol dose of ET-1. When compared with an equimolar dose of ET-1, 300 pmol of ANG II produced a prompt, more marked, but shorter-lived rise in AP with minimal changes in CI, TPRI, RAP, and hematocrit. These results raise the intriguing possibility that endothelin may play a role in both the control of normal vascular smooth muscle tone and in the pathogenesis of vasospastic disorders.

Systemic hemodynamic effects of leukotrienes C4 and D4 in the rat

1983 ◽  
Vol 244 (4) ◽  
pp. H628-H633 ◽  
Author(s):  
M. A. Pfeffer ◽  
J. M. Pfeffer ◽  
R. A. Lewis ◽  
E. Braunwald ◽  
E. J. Corey ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Right Atrial ◽  
Moderate Pressure ◽  
Hemodynamic Effects ◽  
Systemic Hemodynamic ◽  
Leukotriene D4

Although local administration of the sulfidopeptide leukotrienes into cutaneous and coronary vascular beds indicates that these naturally occurring metabolites of arachidonic acid are vasoconstrictors, their systemic administration has produced both pressor and depressor responses. The systemic hemodynamic effects of intravenous leukotriene C4 (LTC4) and leukotriene D4 (LTD4) were assessed in ether-anesthetized rats and compared with the effects produced by equimolar doses (2 X 10(-10) to 4 X 10(-8) mol/kg) of norepinephrine and angiotensin. Mean arterial pressure, right atrial pressure, and cardiac output (electromagnetic flowmetry) were recorded during bolus administrations of these vasoactive compounds. LTC4 and LTD4 had similar hemodynamic effects that were characterized by moderate pressure elevations produced by dose-dependent increases in total peripheral resistance, since cardiac output declined. Although the peak mean arterial pressure levels produced by LTC4 and LTD4 (135 +/- 7 and 129 +/- 5 mmHg, respectively) were less than those by norepinephrine (157 +/- 3 mmHg) and angiotensin (174 +/- 5 mmHg), the peak total peripheral resistance values of LTC4 and LTD4 (2.23 +/- 0.32 and 1.86 +/- 0.17 mmHg X ml-1 X min-1, respectively) were between those of the well-known vasopressors, norepinephrine (1.50 +/- 0.09) and angiotensin (2.72 +/- 0.41). The pressor response to LTC4 and LTD4 was less marked than that to norepinephrine and to angiotensin because of the concomitant reduction in cardiac output. These results indicate that LTC4 and LTD4 are systemic vasoconstrictors with potencies similar to those of norepinephrine and angiotensin.

Angiotensin II modulates frizzled-2 receptor expression in rat vascular smooth muscle cells

2005 ◽  
Vol 108 (6) ◽  
pp. 523-530 ◽  
Author(s):  
Giovanna CASTOLDI ◽  
Serena REDAELLI ◽  
Willy M. M. van de GREEF ◽  
Cira R. T. di GIOIA ◽  
Giuseppe BUSCA ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Ang Ii ◽  
Aortic Smooth Muscle

Ang II (angiotensin II) has multiple effects on vascular smooth muscle cells through the modulation of different classes of genes. Using the mRNA differential-display method to investigate gene expression in rat aortic smooth muscle cells in culture in response to 3 h of Ang II stimulation, we observed that Ang II down-regulated the expression of a member of the family of transmembrane receptors for Wnt proteins that was identified as Fzd2 [Fzd (frizzled)-2 receptor]. Fzds are a class of highly conserved genes playing a fundamental role in the developmental processes. In vitro, time course experiments demonstrated that Ang II induced a significant increase (P<0.05) in Fzd2 expression after 30 min, whereas it caused a significant decrease (P<0.05) in Fzd2 expression at 3 h. A similar rapid up-regulation after Ang II stimulation for 30 min was evident for TGFβ1 (transforming growth factor β1; P<0.05). To investigate whether Ang II also modulated Fzd2 expression in vivo, exogenous Ang II was administered to Sprague–Dawley rats (200 ng·kg−1 of body weight·min−1; subcutaneously) for 1 and 4 weeks. Control rats received normal saline. After treatment, systolic blood pressure was significantly higher (P<0.01), whereas plasma renin activity was suppressed (P<0.01) in Ang II- compared with the saline-treated rats. Ang II administration for 1 week did not modify Fzd2 expression in aorta of Ang II-treated rats, whereas Ang II administration for 4 weeks increased Fzd2 mRNA expression (P<0.05) in the tunica media of the aorta, resulting in a positive immunostaining for fibronectin at this time point. In conclusion, our data demonstrate that Ang II modulates Fzd2 expression in aortic smooth muscle cells both in vitro and in vivo.

scholarly journals Angiotensin II, Hypercholesterolemia, and Vascular Smooth Muscle Cells: A Perfect Trio for Vascular Pathology

2020 ◽  
Vol 21 (12) ◽  
pp. 4525
Author(s):  
Amanda St. Paul ◽  
Cali B. Corbett ◽  
Rachael Okune ◽  
Michael V. Autieri
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Vascular Diseases ◽  
Reduce Blood Pressure ◽  
Vascular Pathology ◽  
Lipid Lowering ◽  
Ang Ii

Cardiovascular disease is the leading cause of morbidity and mortality in the Western and developing world, and the incidence of cardiovascular disease is increasing with the longer lifespan afforded by our modern lifestyle. Vascular diseases including coronary heart disease, high blood pressure, and stroke comprise the majority of cardiovascular diseases, and therefore represent a significant medical and socioeconomic burden on our society. It may not be surprising that these conditions overlap and potentiate each other when we consider the many cellular and molecular similarities between them. These intersecting points are manifested in clinical studies in which lipid lowering therapies reduce blood pressure, and anti-hypertensive medications reduce atherosclerotic plaque. At the molecular level, the vascular smooth muscle cell (VSMC) is the target, integrator, and effector cell of both atherogenic and the major effector protein of the hypertensive signal Angiotensin II (Ang II). Together, these signals can potentiate each other and prime the artery and exacerbate hypertension and atherosclerosis. Therefore, VSMCs are the fulcrum in progression of these diseases and, therefore, understanding the effects of atherogenic stimuli and Ang II on the VSMC is key to understanding and treating atherosclerosis and hypertension. In this review, we will examine studies in which hypertension and atherosclerosis intersect on the VSMC, and illustrate common pathways between these two diseases and vascular aging.

scholarly journals Nox5 in Vascular Smooth Muscle Cells Mediates Ang II‐Induced Renal Fibrosis and Inflammation

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Augusto Montezano ◽  
Francisco Rios ◽  
Livia Camargo ◽  
Roberto Palacios‐Ramirez ◽  
Antoine Tarjus ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Renal Fibrosis ◽  
Muscle Cells ◽  
Ang Ii

Acute and chronic angiotensin hypertension: neural and nonneural components, time course, and dose dependency

1996 ◽  
Vol 271 (1) ◽  
pp. R200-R207 ◽  
Author(s):  
Q. Li ◽  
W. E. Dale ◽  
E. M. Hasser ◽  
E. H. Blaine
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Time Course ◽  
Blood Pressure Reduction ◽  
Chronic Administration ◽  
Hypotensive Effect ◽  
Chronic Hypertension ◽  
Neural Pathways ◽  
Ang Ii ◽  
Chronic Infusion

We examined the mechanisms mediating hypertension in conscious rats during acute and chronic infusion of angiotensin II (ANG II) at pressor doses (50, 100, and 200 ng.kg-1.min-1). Trimethaphan-induced blood pressure reduction was inversely related to the acute dose of ANG II, consistent with a constrictor action of ANG II on vascular smooth muscle and withdrawal of sympathetic tone. During chronic ANG II infusion, the entire increase in mean arterial pressure (MAP) was inhibited by trimethaphan, consistent with neural mediation. During acute ANG II hypertension, the AT1-specific receptor blocker losartan induced a large fall in MAP (64 +/- 4 mmHg) in ganglion-blocked (chlorisondamine) rats, whereas, during chronic ANG II hypertension, losartan had only a small hypotensive effect (11 +/- 3 mmHg). To determine the time course of the change from vascular smooth muscle action to neural action, we measured MAP in response to trimethaphan during the first 24 h of ANG II infusion. After 5 h, the minimal MAP in response to trimethaphan was significantly higher than that before ANG II. After 10 h of infusion, trimethaphan decreased MAP to pre-ANG II levels. That is, the neural component was fully active after only 10 h of infusion in rats. Finally, chronic administration of ANG II resulted in a dose-related increase in MAP that, at all doses, was completely inhibited by trimethaphan. These findings are consistent with ANG II acting primarily on vascular smooth muscle during acute infusion and via neural pathways during chronic treatment. The transition from direct smooth muscle to indirect neural action is rapid in rats (< 10 h), and the MAP and neural responses to ANG II are dose related during chronic hypertension.

K depletion alters angiotensin II receptor expression in vascular smooth muscle cells

1990 ◽  
Vol 258 (5) ◽  
pp. C849-C854 ◽  
Author(s):  
S. L. Linas ◽  
R. Marzec-Calvert ◽  
M. E. Ullian
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Receptor Expression ◽  
Ang Ii ◽  
Surface Receptors ◽  
K Depletion

Dietary K depletion (KD) results in increases in the number of angiotensin II (ANG II) receptors and prevents ANG II-induced downregulation of ANG II receptors in membrane preparations of vessels from KD animals. Because dietary KD results in changes in factors other than K, we K depleted vascular smooth muscle cells (VSMC) in culture to determine the specific effects of KD on ANG II receptor expression and processing. Scatchard analysis of ANG II uptake at 4 degrees C revealed that the number of surface receptors was increased by 37% in cells in which K had been reduced by 45%. This increase also occurred in the presence of cycloheximide. To determine the effect of KD on receptor processing, we measured the number of surface receptors after exposure to ANG II in concentrations sufficient to cause down-regulation. After 30-min exposure to ANG II, the number of surface receptors was reduced by 63% in control cells but only 33% in KD cells. Thirty minutes after withdrawing ANG II, surface binding returned to basal levels in control cells but was still reduced by 20% in KD cells. To determine the functional significance of impaired receptor processing, we measured ANG II uptake at 21 degrees C. Uptake at 21 degrees C depends on the functional number of receptors, i.e., the absolute number of surface receptors and the rate at which receptors are recycled to the surface after ANG II binding. ANG II uptake at 21 degrees C was reduced by 50% in KD cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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