Vascular Biology |
| Abstract |
|---|
|
|
|---|
Key Words: myogenic tone shear stress resistance arteries endothelin hypertension
| Introduction |
|---|
|
|
|---|
Endothelial cells stimulated by hormonal14 or mechanical15 16 17 factors can produce endothelin-1 (ET-1). Mechanical factors such as pressure or wall stretch increase ET-1 gene expression and ET-1 production.16 17 Flow, or shear stress, exerts a flow ratedependent effect on the production of ET-1. A low flow rate or a short-term increase in flow would enhance ET-1 production, whereas a high flow rate or a long-term decrease in flow would diminish ET-1 production.15 Endothelin-1 might be involved in several pathological situations such as preeclampsia,18 renal dysfunction,19 20 sepsis,21 heart failure,22 atherosclerosis,16 cerebral vasospasm,23 24 and aging.25 In spontaneous hypertension, the role of ET-1 is still a matter of debate. No role for ET-1 was found in spontaneously hypertensive rats (SHRs) by Li et al,26 although in mesenteric resistance arteries from SHRs, ETA receptor activation led to higher increases in intracellular calcium.27 Blockade of ETA receptors decreases blood pressure in SHRs.28 In experimental hypertension the importance of ET-1 is better understood. In deoxycorticosterone acetate salthypertensive rats, ET-1 is a determinant of hypertension.26 29 Angiotensin IIinduced hypertension30 as well as the hypertension due to the chronic inhibition of NO synthesis31 is counteracted by the blockade of ETA receptors. Nevertheless, no study has yet clearly determined the consequences of a chronic increase in ET-1 on vascular reactivity. In the different pathological situations given above, ET-1 is involved in a pathological context in which its specific role is difficult to distinguish. Thus, we used a model of chronic infusion of ET-1 in rats to determine the specific effect of ET-1 on basal vascular tone in mesenteric resistance arteries. Because pressure and flow are important in ET-1 production,15 16 we hypothesized that a chronic infusion of ET-1 might interact with pressure-induced (myogenic) tone and flow-induced dilation. Furthermore, both responses to flow and to ET-132 33 involve NO and COX derivatives. Thus, chronic ET-1 might change the proportion of NO and/or COX products in response to flow. We also used hypertensive rats, in which flow-induced dilation in mesenteric resistance arteries involves minimal NO and vasodilator COX derivatives.13 Thus, the effect of chronic ET-1 was investigated under conditions in which NO and COX derivatives were involved (Wistar-Kyoto rats [WKYs]) and under conditions in which NO and COX derivatives were not involved (SHRs).
| Methods |
|---|
|
|
|---|
100 µm in internal
diameter was isolated, cannulated at both ends, and mounted in a
video-monitored perfusion system.33 The artery was bathed
in a 5-mL organ bath containing a physiological
salt solution of the following composition (in mmol/L): 135.0
NaCl, 15.0 NaHCO3, 4.6 KCl, 1.5
CaCl2, 1.2 MgSO4, 11.0
glucose, and 5.0 HEPES. The pH was 7.4, the
PO2 160 mm Hg, and the
PCO2 37 mm Hg. The bath
solution was changed continuously at a rate of 4 mL/min. Perfusion of
the artery with a similar physiological salt
solution was set at a rate ranging from 0 to 150 µL ·
min-1 (under a pressure of 75 mm Hg). The
pressure in both ends of the artery segment was monitored by pressure
transducers (Figure 1
|
Diameter values measured in normal physiological
salt solution were considered as diameter under active tone, or
"active diameter."13 34 35 36 Pressure and diameter
measurements were collected by a Biopac data acquisition system (Biopac
MP 100), recorded, and analyzed on a computer (Apple) using
the Acqknowledge software (Biopac). Results are given in
micrometers or as normalized diameter (percent of passive
diameter under 100 mm Hg). Passive diameter was determined in the
absence of Ca2++EGTA (2 mmol/L)+sodium
nitroprusside (10 µmol/L). Flow-induced relaxation was expressed as
increases in diameter (micrometers) as a function of shear
stress due to flow in vessels subjected to an intraluminal pressure of
75 mm Hg, thus developing an optimal level of myogenic tone.
Shear stress was calculated for each individual segment of artery as
previously described13 :
=4
Q/
r3, where
is viscosity (poise=dyn · s/cm2),
Q is flow (mL/s), and r is radius (cm).
The viability of each vessel was tested before the experimental protocol. The responsiveness of the smooth muscle was assessed by testing the constrictor effect of KCl (80 mmol/L) and phenylephrine (0.1 µmol/L). The presence of the endothelium was assessed by testing the vasodilator effect of acetylcholine (1 µmol/L) after preconstriction of the mesenteric arteries with phenylephrine (0.1 µmol/L), under an intraluminal pressure of 50 mm Hg. Vessels that did not fully contract to KCl (80 mmol/L) and did not fully relax on application of acetylcholine (1 µmol/L) were excluded.
The procedure followed in the care and euthanasia of the rats was in accordance with the European Community standards on the care and use of laboratory animals (Ministère de l'agriculture, France, authorization No. 00577).
Histomorphological Study
The morphometric analysis of the mesenteric resistance
arteries was performed as previously described.36 In
brief, segments of artery, adjacent to those used in the functional
study, were mounted in the arteriograph as described above, and
pressure was set at 100 mm Hg. Vessels were then fixed in 10%
formaldehyde in saline solution for 30 minutes and sectioned
(10-µm-thick sections). Morphometric analysis was performed
with an automated image processor (NS 15000, Microvision). The total
surface area and area of the lumen were measured. This allowed the
calculation of the area of the media.36
Drugs
HEPES, L-NAME, indomethacin, EGTA,
phenylephrine, and acetylcholine were purchased from Sigma
Chemical Co. SQ 29548 was purchase from Biomol. Other reagents were
purchased from Prolabo.
Statistical Analysis
Results are expressed as mean±SEM. Significance of the
differences between the different groups was determined by ANOVA
(1-factor ANOVA or 2-factor ANOVA for consecutive measurements). Means
were compared by a Dunnett's test when appropriate. Probability values
<0.05 were considered to be significant.
| Results |
|---|
|
|
|---|
In isolated mesenteric resistance arteries, stepwise increases in
pressure induced the development of myogenic tone (Figure 1
).
Myogenic tone was higher in SHRs than in WKYs (Figure 1
).
Myogenic tone was not significantly affected by chronic ET-1 in both
strains (not shown). Passive arterial diameter (Figure 1
)
ranged from 78±9 to 169±4 µm in WKYs and from 62±6
to 149±7 µm in SHRs (P<0.001 versus WKYs) for
pressure values ranging from 10 to 150 mm Hg. Chronic ET-1 had no
significant effect on passive diameter in both strains (data not
shown).
Stepwise increases in flow, under a pressure of 75 mm Hg,
significantly attenuated myogenic tone in mesenteric resistance
arteries (Figure 2
). Flow-induced
dilation was significantly lower in SHRs than in WKYs (Figure 2
). The NO synthesis blocker L-NAME (100 µmol/L)
significantly attenuated flow-induced dilation in WKYs (Figures 3
and 4
).
L-NAME (100 µmol/L) had a significantly lower effect on
flow-induced dilation in SHRs than WKYs (Figure 4
). The COX
inhibitor indomethacin (3 µmol/L)
significantly attenuated flow-induced dilation in WKYs (Figure 3
) and SHRs (Figure 5
). Chronic
ET-1 significantly increased flow-induced dilation in SHRs (Figure 2
),
without significantly affecting the response to flow in WKYs
(Figure 2
). In both WKYs (Figure 4
) and SHRs (Figure 6
), chronic ET-1 increased the proportion
of flow-induced dilation sensitive to L-NAME. The proportion of
flow-induced dilation sensitive to indomethacin (Figure 6
)
was also increased by chronic ET-1 in SHRs (with no effect in
WKYs; not shown).
|
|
|
|
|
The thromboxane
A2PGH2 receptor blocker
SQ 29548 (1 µmol/L) significantly increased flow-induced
dilation in mesenteric resistance arteries from SHRs (Figure 7
). In WKYs, SQ 29548 (1 µmol/L)
had no significant effect on flow-induced dilation (Figure 7
).
The chronic treatment of rats with ET-1 did not significantly affect SQ
29548 (1 µmol/L)-dependent, flow-induced dilation in either strain
(Figure 7
).
|
The presence of the endothelium was confirmed by testing the vasodilator effect of acetylcholine (1 µmol/L) after preconstriction of the mesenteric resistance arteries with phenylephrine (0.1 µmol/L). Phenylephrine (0.1 µmol/L at 50 mm Hg) induced a decrease in diameter from 121±12 to 44±8 µm (n=8) in WKYs and from 112±10 to 40±9 µm (n=8) in SHRs. The further addition of acetylcholine (1 µmol/L) induced an increase in diameter from 44±8 to 138±11 µm (n=8) in WKYs and from 40±9 to 103±10 µm (n=8) in SHRs (P<0.05 versus WKYs). Phenylephrine (0.1 µmol/L)-induced tone and acetylcholine (1 µmol/L)-induced dilation were not significantly affected by chronic ET-1 in either WKYs or SHRs (not shown). The constrictor effect of KCl (80 mmol/L) was not significantly affected by chronic ET-1 in both SHRs and WKYs (not shown).
Sodium nitroprusside induced a dilation that was not significantly affected by chronic ET-1. In all groups, the maximal dilation was 100%. In WKYs, the IC50 was 2.6±0.33 nmol/L in controls and 1.5±0.27 nmol/L in the chronic ET-1 group. In SHRs, the IC50 was 5.1±1.1 nmol/L in controls and 4.2±1.0 nmol/L in the chronic ET-1 group.
The histomorphometric analysis of the mesenteric resistance arteries showed that chronic ET-1 significantly increased the thickness of the media tunica (5.7±0.5 versus 7.8±0.7 µm, n=9, in WKYs, P<0.01; and 6.9±0.4 versus 8.5±0.6 µm, n=9, in SHRs, P<0.03). The media to lumen ratio was also significantly higher in ET-1treated rats (0.19±0.04 versus 0.33±0.04, n=9, in WKYs, P<0.05; and 0.32±0.05 versus 0.48±0.06, n=9, in WKYs, P<0.05).
| Discussion |
|---|
|
|
|---|
In mesenteric resistance arteries isolated from SHRs, we found a higher myogenic tone and a lower response to flow, compared with WKYs. This result is in agreement with previous studies.12 13 36 37 38 In addition, in SHRs the response to flow depends less on the production of NO (vide infra and References 12 and 1312 13 ). In SHRs, the production of COX derivatives in response to flow has been shown to be higher in resistance arteries from gracilis muscle12 and lower in mesenteric resistance arteries.13 In mesenteric resistance arteries from SHRs, we have previously shown a lower production of vasodilator COX products and a higher production of vasoconstrictor COX products.12 In the present study, indomethacin-sensitive, flow-induced dilation was increased by chronic ET-1 in SHRs but not in WKYs. Different type of COX products are involved in flow-induced dilation in SHRs, as previously shown.13 This could explain the difference between the 2 strains. Moreover, ET-1 has been shown to activate COX derivative production. The production of vasodilator prostanoids is activated by ET-1 in the rat aorta,39 lung vessels,40 mesenteric arteries,41 and afferent arterioles,42 whereas vasoconstrictor prostanoids are involved in ET-1induced contraction in the rat aorta43 and in afferent arterioles from SHRs.42 We found an increased sensitivity of flow-induced dilation to indomethacin in SHRs chronically treated with ET-1. Thus, in SHRs, chronic ET-1 might either activate the production of vasodilator COX derivatives or downregulate vasoconstrictor COX product(s). Nevertheless, this latter possibility may not apply, since the increase in flow-induced dilation due to the thromboxanePGH2 receptor blocker SQ 29548 in SHR arteries was not affected by chronic ET-1.
The participation of NO in flow-induced dilation was higher after chronic ET-1. This might be a response to the increased tone due to ET-1. Because ET-1 can participate in the response to flow as a contractile factor,44 an increased NO production might counterbalance the ET-1induced tone. In addition, we found that the relaxation to the NO donor sodium nitroprusside was not affected by chronic ET-1. Thus, a nonspecific effect of chronic ET-1 on the cGMP pathway can be excluded.
Finally, chronic ET-1 increased (in SHRs) or did not change (in WKYs) the amplitude of flow-induced dilation, despite an increase in blood pressure in both strains. This increase was significant in SHRs for shear stress values equal to 20 dyn/cm2 and higher. In resistance arteries, shear stress may vary greatly, as flow may locally change rapidly from low to high values (up to 100 dyn/cm2 and even to negative values if flow reverses.45 In all other animal models of hypertension, a decreased endothelium-dependent dilation has been described. Both flow-induced dilation12 13 34 46 and agonist-induced dilation47 are affected in hypertensive animals. This emphasizes that the change in NO and prostanoid production in response to flow is specific to ET-1. Another possibility is that flow-induced dilation may not necessarily be a determinant of blood pressure. In agreement with this possibility, we have shown in mice lacking the gene for vimentin that flow-induced dilation was decreased despite a normal blood pressure.35 Nevertheless, chronic ET-1 increased the wall to lumen ratio in mesenteric arteries, which is a characteristic of a vascular adaptation to a high blood pressure.36
The duration of the treatment with ET-1 (2 weeks) and the dose used (5 ng · kg-1 · min-1) were validated in previous work.32 48 49 A 1-week-long treatment with concentrations of ET-1 ranging from 1 to 5 ng · kg-1 · min-1 induced a doubling of the plasma ET-1 concentration. Such an increase in plasma ET-1 has been described in several pathological situations.50 51 52 53 54
In conclusion, the main effect of chronic ET-1 was to increase L-NAMEsensitive, flow-induced dilation in mesenteric resistance arteries in WKYs and SHRs. In addition, in SHRs the dilator response to flow was improved after chronic ET-1.
| Acknowledgments |
|---|
Received June 24, 1998; accepted January 25, 1999.
| References |
|---|
|
|
|---|
2.
Kuo L, William MC, Davis MJ. Interaction of
pressure-and flow-induced responses in porcine coronary
resistance vessels. Am J Physiol. 1991;261:H1706H1715.
3. Johnson PC. The myogenic response. In: Bevan JA, Halpern W, Mulvany MJ, eds. The Resistance Vasculature. Totowa, NJ: Humana Press; 1991:159168.
4. Osol G. Myogenic properties of blood vessels in vitro. In: Bevan JA, Halpern W, Mulvany MJ, eds. The Resistance Vasculature. Totowa, NJ: Humana Press; 1991:143157.
5.
D'Angelo G, Meininger GA. Transduction mechanisms
involved in the regulation of myogenic tone activity.
Hypertension. 1994;23:10961105.
6. Bevan JA, Henrion D. Pharmacological implications of the influence of intraluminal flow on smooth muscle tone. Annu Rev Pharmacol Toxicol. 1994;34:173190.[Medline] [Order article via Infotrieve]
7.
Segal SS. Cell-to-cell communication coordinates blood
flow control. Hypertension. 1991;23:11131120.
8.
Smiesko V, Johnson PC. The arterial lumen
is controlled by flow-related shear stress. News Physiol
Sci. 1993;8:3438.
9.
Kuo L, Davis MJ, Chillian WM.
Endothelial modulation of arteriolar tone. News
Physiol Sci. 1992;7:59.
10.
Hecker M, Mulsch A, Bassenge E, Busse R.
Vasoconstriction and increased flow: two principal mechanisms of shear
stress-dependent endothelial autacoid release.
Am J Physiol. 1993;265:H828H833.
11.
Koller A, Sun D, Kaley G. Role of shear stress and
endothelial prostaglandins in flow and
viscosity induced dilation of arterioles in vitro. Circ Res. 1993;72:12761284.
12.
Koller A, Huang A. Impaired nitric oxide-mediated
flow-induced dilation in arterioles of spontaneously hypertensive rats.
Circ Res. 1994;74:416421.
13.
Matrougui K, Maclouf J, Lévy BI, Henrion D.
Impaired nitric oxide and prostaglandin-mediated response
to flow in resistance mesenteric arteries of hypertensive rats.
Hypertension. 1997;30:942947.
14. Chen L, McNeil R, Wilson TW, Gopalakrisnan V. Differential effects of phosphoramidon on contractile responses to angiotensin II in rat blood vessels. Br J Pharmacol. 1995;114:15991604.[Medline] [Order article via Infotrieve]
15.
Kuchan MJ, Frangos JA. Shear stress regulates
endothelin-1 release via protein kinase C and cGMP in cultured
endothelial cells. Am J Physiol. 1993;264:H150H156.
16.
Hasdai D, Holmes DR Jr, Garratt KN, Edwards WD, Lerman
A. Mechanical pressure and stretch release endothelin-1 from human
atherosclerotic coronary arteries in vivo.
Circulation. 1997;95:357362.
17.
Hishikawa K, Nakaki T, Marumo T, Suzuki H, Kato R,
Saruta T. Pressure enhances endothelin-1 release from cultured human
endothelial cells. Hypertension. 1995;25:449452.
18.
Lüscher TF, Seo B, Bühler FR. Potential
role of endothelin in hypertension. Hypertension. 1993;21:752757.
19.
Karam H, Heudes D, Bruneval P, Gonzales MF,
Löefler BM, Clozel M, Clozel JP. Endothelin antagonism in
end-organ damage of spontaneously hypertensive rats.
Hypertension. 1996;28:379385.
20. Rabelink TJ, Kaasjager KA, Stroes ES, Koomans HA. Endothelin in renal pathophysiology: from experimental to therapeutic application. Kidney Int. 1996;50:18271833.[Medline] [Order article via Infotrieve]
21. Sharma AC, Motew SJ, Farias S, Alden KJ, Bosmann HB, Law WR, Ferguson JL. Sepsis alters myocardial and plasma concentrations of endothelin-1 and nitric oxide in rats. J Mol Cell Cardiol. 1997;29:14691477.[Medline] [Order article via Infotrieve]
22. Goto K, Hama H, Kasuya Y. Molecular pharmacology and pathophysiological significance of endothelin. Jpn J Pharmacol. 1996;72:261290.[Medline] [Order article via Infotrieve]
23. Cosentino F, Katusic ZS. Does endothelin-1 play a role in the pathogenesis of cerebral vasospasm? Stroke. 1994;25:904908.[Abstract]
24.
Zuccarello M, Boccaletti R, Tosun M, Rapoport RM. Role
of extracellular Ca2+ in subarachnoid
hemorrhage-induced spasm of the rabbit basilar artery.
Stroke. 1996;27:18961902.
25. Battisteslli S, Manasse G, Gaudio R, Borgogni T, Forconi S. Circulating endothelin immunoreactivity in the elderly. Clin Haemorheol. 1996;16:653660.
26.
Li JS, Larivière R, Schiffrin EL. Effect of a
non-selective endothelin antagonist on vascular remodeling
in DOCA-salt hypertensive rats. Hypertension. 1994;24:183188.
27. Sharifi AM, Schiffrin EL. Endothelin receptors mediating vasoconstriction in rat pressurized small arteries. Can J Physiol Pharmacol. 1996;74:934939 .[Medline] [Order article via Infotrieve]
28. Ohlstein EH, Douglas SA, Ezekiel M, Gellai M. Antihypertensive effects of the endothelin receptor antagonist BQ-123 in conscious spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1993;22(suppl 8):S321S324.
29. Schiffrin EL, Lariviere R, Li JS, Sventek P. Enhanced expression of the endothelin-1 gene in blood vessels of DOCA-salt hypertensive rats: correlation with vascular structure. J Vasc Res. 1996;33:235248.[Medline] [Order article via Infotrieve]
30.
d'Uscio LV, Moreau P, Shaw S, Takase H, Barton M,
Luscher TF. Effects of chronic ETA-receptor blockade in
angiotensin II-induced hypertension.
Hypertension. 1997;29:435441.
31. Richard V, Kaeffer N, Hogie M, Tron C, Blanc T, Thuillez C. Role of endogenous endothelin in myocardial and coronary endothelial injury after ischaemia and reperfusion in rats: studies with bosentan, a mixed ETA-ETB antagonist. Br J Pharmacol. 1994;113:869876.[Medline] [Order article via Infotrieve]
32.
Mortensen LH, Pawloski CM, Kanagy NL, Fink GD. Chronic
hypertension produced by infusion of endothelin in rats.
Hypertension. 1990;15:729733.
33. Halpern W, Osol G, Coy GS. Mechanical behavior of pressurized in vitro prearteriolar vessels determined with a video system. Ann Biomed Eng. 1994;12:463479.
34. Henrion D, Dechaux E, Dowell FJ, Maclouf J, Samuel JL, Lévy BI, Michel JB. Alteration of flow-induced dilation in mesenteric resistance arteries of L-NAME treated rats is partially associated to induction of cyclooxygenase-2. Br J Pharmacol. 1997;121:8390.[Medline] [Order article via Infotrieve]
35. Henrion D, Terzi F, Matrougui K, Boulanger C, Duriez M, Boulanger C, Colucci-Guyon E, Babinet C, Briand P, Friedlander G, Poitevin P, Lévy BI. Impaired flow-induced dilation in mesenteric resistance arteries from mice lacking vimentin. J Clin Invest. 1997;100:29092914.[Medline] [Order article via Infotrieve]
36. Lévy BI, Benessiano J, Henrion D, Caputo L, Heymes C, Duriez M, Poitevin P, Samuel JL. Chronic blockade of AT2-subtype receptors prevents the effect of angiotensin II on the rat vascular structure. J Clin Invest. 1996;98:418425.[Medline] [Order article via Infotrieve]
37.
Falcone JC, Granger HJ, Meininger GA. Enhanced myogenic
activation in skeletal muscle arterioles from spontaneously
hypertensive rats. Am J Physiol. 1993;265:H1847H1855.
38.
Antony I, Lerebours G, Nitenberg A. Loss of
flow-dependent coronary artery dilation in patients with
hypertension. Circulation. 1995;91:16241628.
39.
Wright HM, Malik KU. Prostacyclin synthesis elicited by
endothelin-1 in rat aorta is mediated by an ETA receptor via influx of
calcium and is independent of protein kinase C.
Hypertension. 1995;26:10351040.
40. Lal H, Woodward B, Williams KI. Investigation of the contributions of nitric oxide and prostaglandins to the actions of endothelins and sarafotoxin 6c in rat isolated perfused lungs. Br J Pharmacol. 1996;118:19311938.[Medline] [Order article via Infotrieve]
41.
Dohi Y, Lüscher TF. Endothelin in hypertensive
resistance arteries: intraluminal and extraluminal dysfunction.
Hypertension. 1991;18:543549.
42. Gonzalez MR, Villa E, Garcia-Robles R, Angulo J, Peiro C, Marin J, Sanchez-Ferrer CF. Effects of indomethacin and iloprost on contraction of the afferent arterioles by endothelin-1 in juxtamedullary nephron preparations from normotensive Wistar-Kyoto and spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1996;28:809816.[Medline] [Order article via Infotrieve]
43.
Taddei S, Vanhoutte PM. Role of
endothelium in endothelin-evoked contractions in the
rat aorta. Hypertension. 1993;21:915.
44. Matrougui K, Lévy BI, Henrion D. Involvement of angiotensin II type 2 and endothelin-1 type A receptor stimulation in response to shear stress in rat resistance arteries in situ (abstract). Circulation. 1997;96(suppl I):I-478.
45. Davies PF. Flow-mediated endothelial mechanotransduction. Physiol Rev. 1995;75:519560.
46.
Boegehold MA. Effect of dietary salt on arteriolar
nitric oxide in striated muscle of normotensive rats. Am J
Physiol. 1993;264:H1810H1816.
47. Noll G, Tschudi M, Nava E, Lüscher TF. Endothelium and high blood pressure. Int J Microcirc Clin Exp. 1997;17:273279.[Medline] [Order article via Infotrieve]
48.
Thorin E, Cernacek P, Dupuis J. Endothelin-1 regulates
tone of isolated small arteries in the rat: effect of
hyperendothelinemia. Hypertension. 1998;31:10351041.
49.
Wilkins FC Jr, Kassab S, Kato T, Mizelle HL, Opgenorth
TJ, Granger JP. Chronic endothelin-induced pressor and renal actions in
conscious dogs do not require altered ANG II formation. Am J
Physiol. 1995;268:R395R402.
50. Hoffmann E, Assennato P, Donatelli M, Colletti I, Valenti TM. Plasma endothelin-1 levels in patients with angina pectoris and normal coronary angiograms. Am Heart J. 1998;135:684688.[Medline] [Order article via Infotrieve]
51. Letizia C, Iannaccone A, Cerci S, Santi G, Cilli M, Coassin S, Pannarale MR, Scavo D. Circulating endothelin-1 in non-insulin-dependent diabetic patients with retinopathy. Horm Metab Res. 1997;29:247251.[Medline] [Order article via Infotrieve]
52.
Vlachojannis J, Tsakas S, Petropoulou C, Kurz P.
Increased renal excretion of endothelin-1 in nephrotic patients.
Nephrol Dial Transplant. 1997;12:470473.
53.
Filep JG, Bodolay E, Sipka S, Gyimesi E, Csipo I,
Szegedi G. Plasma endothelin correlates with
antiendothelial antibodies in patients with mixed
connective tissue disease. Circulation. 1995;92:29692974.
54.
Wieczorek I, Haynes WG, Webb DJ, Ludlam CA, Fox KA.
Raised plasma endothelin in unstable angina and non-Q wave myocardial
infarction: relation to cardiovascular outcome.
Br Heart J. 1994;72:436441.
This article has been cited by other articles:
![]() |
N. Kleinstreuer, T. David, M. J. Plank, and Z. Endre Dynamic myogenic autoregulation in the rat kidney: a whole-organ model Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1453 - F1464. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Liu, S. Mather, Y. Huang, C. J. Garland, and X. Yao Extracellular ATP facilitates flow-induced vasodilatation in rat small mesenteric arteries Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1688 - H1695. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Besnard, J. Bakouche, Y. Lemaigre-Dubreuil, J. Mariani, A. Tedgui, and D. Henrion Smooth Muscle Dysfunction in Resistance Arteries of the Staggerer Mouse, a Mutant of the Nuclear Receptor ROR{alpha} Circ. Res., April 19, 2002; 90(7): 820 - 825. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. B. Taner, S. R. Severson, P. J. M. Best, A. Lerman, and V. M. Miller Treatment with endothelin-receptor antagonists increases NOS activity in hypercholesterolemia J Appl Physiol, March 1, 2001; 90(3): 816 - 820. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Loufrani, K. Matrougui, D. Gorny, M. Duriez, I. Blanc, B. I. Levy, and D. Henrion Flow (Shear Stress)-Induced Endothelium-Dependent Dilation Is Altered in Mice Lacking the Gene Encoding for Dystrophin Circulation, February 13, 2001; 103(6): 864 - 870. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Besnard, J. Bakouche, Y. Lemaigre-Dubreuil, J. Mariani, A. Tedgui, and D. Henrion Smooth Muscle Dysfunction in Resistance Arteries of the Staggerer Mouse, a Mutant of the Nuclear Receptor ROR{alpha} Circ. Res., April 19, 2002; 90(7): 820 - 825. [Abstract] [Full Text] [PDF] |
||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
ATVB Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 1999 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |