ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Mohammed Amrani
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kelsall, C. J.
Right arrow Articles by Singer, D. R.J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kelsall, C. J.
Right arrow Articles by Singer, D. R.J.

Ann Thorac Surg 2005;80:1347-1351
© 2005 The Society of Thoracic Surgeons

Original article: Cardiovascular

C-Type Natriuretic Peptide Relaxes Human Coronary Artery Bypass Grafts Preconstricted by Endothelin-1

Christopher J. Kelsall, PhD a , * , Adrian H. Chester, PhD a , Mohammed Amrani, FRCS a , Donald R.J. Singer, MD b

a Department of Cardiothoracic Surgery, Heart Science Centre and Harefield Hospital, Harefield, Middlesex, United Kingdom
b Leicester-Warwick Medical School, University of Warwick, Coventry, United Kingdom

Accepted for publication January 28, 2005.

* Address reprint requests to Dr Kelsall, Department of Cardiothoracic Surgery, Heart Science Centre, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK (Email: c.kelsall{at}imperial.ac.uk).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: Endothelin is implicated in graft spasm after coronary artery bypass grafting. We assessed reversal by the endothelium-derived vasodilator C-type natriuretic peptide of prior contraction of radial artery and other vessels commonly used for coronary artery bypass surgery.

METHODS: Segments of human radial artery, saphenous vein, and internal mammary artery were mounted in organ baths after removal from patients undergoing cardiac surgery (n = 34; 64 ± 2 years). Effects of increasing concentrations of C-type natriuretic peptide (with or without aprotinin, 1,000 U/mL) on endothelin-induced contraction were compared with acetylcholine, sodium nitroprusside, and papaverine.

RESULTS: C-type natriuretic peptide relaxed endothelin precontraction in all vessels (F = 17.8, 36.3, and 48.4, respectively; p < 0.001), with maximum relaxations of 44%, 54%, and 66% in saphenous vein, internal mammary artery, and radial artery, respectively. Aprotinin did not affect relaxation to C-type natriuretic peptide. Acetylcholine relaxed the saphenous vein weakly, with maximal relaxation of 9% at 10–6M. However, the radial artery and internal mammary artery relaxed strongly to acetylcholine. The highest concentration of papaverine completely relaxed all vessels, but responses were less sensitive than to sodium nitroprusside or acetylcholine.

CONCLUSIONS: C-type natriuretic peptide reverses endothelin-induced constriction in arterial and venous conduits used for coronary artery bypass, particularly the radial artery. Proteolytic breakdown of C-type natriuretic peptide by local vascular enzymes appears of little importance in vitro. This signals the therapeutic potential of using C-type natriuretic peptide as an antagonist of graft vasospasm after coronary artery bypass surgery.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Coronary artery bypass graft (CABG) operations improve the health and quality of life of many patients with ischemic heart disease. A continuing problem, however, is that clinical benefits of the procedure can be compromised by perioperative or postoperative vasospasm, which may lead to arrhythmias, cardiac ischemia, and infarction. Vasoconstriction of the graft vessel may be influenced by risk factors for cardiovascular disease [1] and is associated with a disruption in the balance of vasodilator and vasoconstrictor influences. During surgery, the endogenous release of vasoconstrictors such as thromboxane A2, angiotensin II, and endothelin may increase, while there may also be impaired release of endothelial-derived dilators as a result of endothelial dysfunction in the graft [2].

A number of pharmacologic strategies have been adopted to dilate the vessel wall prior to and during grafting. Vasospasm has previously been treated by perioperative or postoperative targeted infusion of vasodilators [3] and by use of papaverinized blood, calcium channel antagonists, nitric oxide donors, angiotensin-converting enzyme inhibitors, and irreversible antagonists of adrenoceptors [3–6]. However, much of the dilator action of papaverine is lost within 8 hours [7] and receptor antagonism of endogenous vasoconstriction requires the use of a multiple number of drugs. An alternative approach to address the problem of postoperative vasospasm is to consider whether making use of an endogenous vasodilator could effectively prevent vasospasm.

C-type natriuretic peptide (CNP) is produced by human vascular endothelial cells, and is released ablumenally to mediate vasodilation by increasing levels of cyclic guanosine monophosphate (cGMP), via natriuretic peptide B receptors (NPRB) on the vascular smooth muscle. The natriuretic peptide system is considered important for counteracting the chronic vasoconstrictor effects of the renin-angiotensin system and vasopressin in the maintenance of vascular tone [8].

Vasospasm may also occur because of greater responsiveness to vasoconstrictors, among which endothelin is an important candidate. Endothelin is capable of acting as a potent vasoconstrictor of the saphenous vein [9], the internal mammary artery (IMA) [10], and the radial artery (RA) [11]. Circulating and artery tissue levels of endothelin are increased during and after CABG [12–15], which may be as a consequence of ischemia-reperfusion injury [12] and may be increased by cardiovascular risk factors [15, 16]. Increases in endothelin immunoreactivity in biopsies of graft artery are associated with a greater incidence of localized transient ischemic events after CABG [15] and with venous and artery graft damage [17]. Endothelin may also be able to potentiate constrictor effects of other vasoconstrictor stimuli [18].

The aims of this study were to examine the ability of CNP to reverse endothelin-induced constriction of the radial artery in comparison with other graft vessels and to compare the efficacy of CNP against that of other important vasodilators. In addition, we investigated the extent to which any relaxant effects of CNP on endothelin constriction are modified in vitro by neutral endopeptidase inhibition.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Acknowledgments
 References
 
Vascular Tissue
We studied segments of vessels obtained from patients undergoing CABG surgery who had given written informed consent. This study complies with the Declaration of Helsinki. Local ethical committee approval was given for use of human tissue. A total of 86 vessel segments were removed from 34 patients (age 64 ± 2 years, standard error of the mean [SEM]) at the time of CABG. The radial artery, saphenous vein (SV), and internal mammary artery were collected in sterile Hank's solution containing 25 mm 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid (HEPES) buffer and dissected free of surrounding tissue. Some specimens were stored for up to 24 h at 4°C prior to use in organ bath experiments. None of the measured parameters indicated any difference in tissue function between grafts used immediately after surgery and those stored for 24 h prior to use.

Organ bath studies were carried out as published previously [19]. Briefly, segments (3–5 mm in length) of SV, IMA, or RA were mounted between two metal hooks in individual organ baths containing modified Tyrode's solution (NaCl 136.9 mM, NaHCO3 11.9, KCl 2.7, NaH2PO4 0.4, MgCl2 2.5, CaCl2 2.5, glucose 11.1, and disodium ethylenediaminetetraacetic acid [EDTA] 0.04), which was maintained at 37°C while being gassed with 95% O2–5% CO2. Each segment was given an initial pretension of 40 to 50 milliNewtons (mN), then allowed to relax completely over a period of 30 to 60 minutes. This was followed by addition of 90 mm KCl to depolarize the vessel segments. Once a stable contraction had been attained, the KCl was washed out with Tyrode's solution. When a stable baseline had been reestablished, vessel segments were stretched and then depolarized with KCl again. This was done to assess tissue viability and to attain consistent responses from each vessel segment.

Each vessel segment was then contracted by adding endothelin to the bath to achieve a concentration of 3 x 10–8M. If this was insufficient to induce a sustained contraction (10 minute plateau response), the bath concentration of endothelin was increased to 10–7M, such that the contraction was equivalent to approximately 50% to 80% of that of 90 mm KCl.

After contraction with endothelin, vessel segments were exposed to increasing concentrations of vasorelaxing drugs: C-type natriuretic peptide (Bachem, UK), with or without the neutral endopeptidase inhibitor aprotinin (Ferring Pharmaceuticals, Langley, UK); acetylcholine (ACh; Sigma); papaverine (Sigma); and the nitric oxide donor sodium nitroprusside (SNP; Sigma). All drugs were applied in 1/2log10 units, from 10–9M for all drugs up to 10–6M for CNP, 10–5M for SNP, and 10–4M for ACh and papaverine. The responses were measured in stepwise relaxations; after the effects of each concentration had leveled off (5–10 minutes after application), the next concentration was added to the bath. Responses to ACh were used to determine whether endothelial damage had occurred as a result of surgical manipulation or preexperimental preparation of the tissue. Aprotinin, which is used clinically to inhibit neutral endopeptidase-dependent metabolism of natriuretic peptides in plasma, was added to the bath (where applicable) 5 minutes prior to addition of CNP, to achieve a bath concentration of 1,000 kallikrein units/mL. Aprotinin caused a slight, transient relaxation on occasion, but in every instance this effect had recovered within 5 minutes. After maximal relaxation had been achieved in each vascular ring, 10–5M SNP was added to the bath to elicit the maximal relaxation achievable by each individual segment. Concentration-response curves for a given vessel segment were not repeated, and did not involve use of more than one vasorelaxing drug.

Analysis
Relaxation responses to CNP, ACh, and papaverine were expressed as a percentage of maximal relaxation by SNP (10–5M, 100%), for each vascular ring, and pEC50 (concentration producing a 50% inhibition of the maximal contractile response; current terminology for drug potency, replacing pD2) values were calculated for all response curves except CNP and papaverine, which did not achieve a true maximum response at the highest concentration used. All Emax and pEC50 values are presented as mean ± SEM. Comparisons of pEC50 values were made using one way analysis of variance (ANOVA). Comparisons of CNP and CNP + aprotinin dose response curves were made by 2-way repeated measures ANOVA (analysis by concentration, analysis by treatment). All ANOVA were followed by Scheffe's posthoc test. These statistics were performed using SPSS 11.5 for Windows (SPSS, Chicago, IL).


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Acknowledgments
 References
 
Vascular Tension
Addition of 90 mm KCl to each segment induced an average contraction from resting tension of 91 ± 7 mN in SV (n = 30), 30 ± 4 mN in IMA (n = 29), and 93 ± 12 mN in RA (n = 27). Endothelin (10–7M) induced a potent contraction in rings of the saphenous vein (44 ± 7 mN, n = 30), the internal mammary artery (23 ± 2 mN, n = 29), and the radial artery (44 ± 6 mN, n = 27). Sodium nitroprusside relaxed precontracted vascular rings to a level below the baseline tone preceding the contraction to endothelin (SV: 171 ± 30%, n = 5; IMA: 145 ± 22%, n=5; RA: 113 ± 3%, n = 5).

C-Type Natriuretic Peptide Responses
C-type natriuretic peptide induced a concentration-dependent relaxation of endothelin-induced precontraction in SV (F = 17.8, p < 0.001 by concentration; Fig 1), in IMA (F = 36.3, p < 0.001; Fig 2), and in RA (F = 48.4, p < 0.001; Fig 3), resulting in relaxations at 10–6M CNP of 44%, 54%, and 66% of SNP-induced relaxation, respectively. The presence of aprotinin in the bath did not significantly affect the dose response curve for CNP in SV (F = 0.012, p = 0.92; by treatment), IMA (F = 0.79, p = 0.42), or RA (F = 2.06, p = 0.25).



View larger version (18K):
[in this window]
[in a new window]
  		Fig 1. Responses to vasodilators in rings of saphenous vein preconstricted by 10–7 M endothelin-1. Number in parentheses. {blacksquare} = CNP (5); {square} = CNP + aprotinin (6); {blacktriangleup} = SNP (5); x = ACh (4); {circ} = papaverine (6). (ACh = acetylcholine; CNP = C-type natriuretic peptide; SNP = sodium nitroprusside.)

 


View larger version (20K):
[in this window]
[in a new window]
  		Fig 2. Responses to vasodilators in rings of internal mammary artery segments preconstricted by 10–7 M endothelin-1. Number in parentheses. {blacksquare} = CNP (5); {square} = CNP + aprotinin (6); {blacktriangleup} = SNP (5); x = ACh (6); {circ} = papaverine (6). (ACh = acetylcholine; CNP = C-type natriuretic peptide; SNP = sodium nitroprusside.)

 


View larger version (22K):
[in this window]
[in a new window]
  		Fig 3. Responses to vasodilators in rings of radial artery segments preconstricted by 10–7 M endothelin-1. Number in parentheses. {blacksquare} = CNP (6); {square} = CNP + aprotinin (6); {blacktriangleup} = SNP (5); x = ACh (6); {circ} = papaverine (4). (ACh = acetylcholine; CNP = C-type natriuretic peptide; SNP = sodium nitroprusside.)

 
Acetylcholine Responses
Acetylcholine relaxed SV very weakly, with concentrations greater than 10–6 M tending to cause recontraction. The greatest relaxation was 9 ± 16% of the SNP response (Fig 1). In contrast, acetylcholine caused a markedly greater maximum relaxation in IMA (67%, Fig 2) and in RA (71%, Fig 3). Furthermore, a significant difference in potency is expressed clearly by the difference in pEC50 values (6.7 ± 0.4 for SV compared to 7.9 ± 0.3 [p < 0.05 vs SV] and 8.0 ± 0.1 [p < 0.05 vs SV] for IMA and RA, respectively).

Papaverine Responses
Papaverine caused a complete relaxation in all vessel types at 10–4M (Figs 1–3), as did SNP at 10–5M (Figs 1–3). In all cases, the potency of the papaverine response appeared markedly lower than for SNP.


   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Acknowledgments
 References
 
CNP in Human Studies
The present study is the first to report on the potent reversal of contraction by C-type natriuretic peptide in the human radial artery, an increasingly popular graft in CABG operations. Direct effects of CNP on tone in other human vessels have been studied previously; CNP reversed endothelin-induced constriction of human resistance coronary arteries to a similar degree to that seen in the present study [20]. The ability of CNP to reverse endothelin-induced constriction has also been investigated in SV and IMA from CABG patients [21], using the same maximum concentration of CNP as in the present study. While the above response in IMA supports our observations, there is a disparity with respect to relaxation of SV by CNP. Protter and colleagues [21] were able to elicit only approximately 35% relaxation of endothelin-induced constriction by CNP, normalized to papaverine responses, in SV, compared against 60% in IMA. Hence, in the current study, there was a more equal relaxation to CNP between IMA and SV. The reasons for these differences are not clear, but Protter and colleagues apparently acquired tissue from cases other than CABG, and specimens for each study group were derived from only 3 patients. Their use of relaxation to papaverine to normalize responses to CNP is another potentially confounding factor, given that CNP and SNP both cause relaxation via guanylate cyclase/cGMP, while papaverine is thought to act directly on Ca2+ channels to elicit smooth muscle relaxation.

A limitation of an in vitro study is that the results cannot take account of the complex counterbalancing biochemical pathways in vivo, which will reflect the relative roles of all vasodilators and vasoconstrictors in the circulation. Therefore, measuring the ability of one natriuretic peptide to counter the constrictor effects of one endogenous vasoconstrictor is limited in scope. However, human forearm blood flow studies have also demonstrated the ability of CNP to show potent vasodilation in vivo [22] and to counter vasoconstrictor influences [23]. In addition, such studies have shown that CNP may be important, relative to other natriuretic peptides, in preserving vasorelaxation in pathophysiological conditions such as congestive heart failure [24]. The ability of CNP to reverse endothelin-induced constriction in vitro relates to the ability of CNP to alter basal tone in vivo, where endothelin is one of the major constrictor influences on vascular tone.

A second limitation of this study is that the physiological concentrations of CNP to which vascular smooth muscle is exposed in vivo cannot be measured. C-type natriuretic peptide in the human circulation is normally approximately 6 pg/mL plasma [25], but this does not accurately reflect the effective concentration of a peptide that is released predominantly in the ablumenal direction from endothelium to smooth muscle. However, the localized concentration of CNP at the site of effect is likely to be significantly greater than in circulation. The receptor-signaling pathway for autocrine CNP-induced relaxation may be complex; CNP relaxation is endothelium-independent in pig coronary artery [26] and dog femoral vein [27], possibly acting via cGMP and calcium-activated potassium channels [27]. However, CNP has also been shown to act as a natriuretic peptide receptor C (NPRc)-dependent hyperpolarizing factor in rat coronary flow [28], but its capacity to function in the absence of endothelium was not tested. The NPRc is not coupled to guanylate cyclase, so its activation cannot produce cGMP. These different pathways for smooth muscle relaxation by CNP require elucidation in a single model.

Gene Transfer of CNP
The paracrine activity of CNP in vivo is unique among endogenous vasodilators, but in order to take advantage of this clinically, vasospasm in patients might be treated by a localized gene transfer approach. A number of studies have explored effects of gene-transferring CNP into vascular tissue, under both normal and disease conditions. Gene-transferred CNP has been shown to promote angiogenesis in ischemic muscle without apparent adverse effects [29], and to increase the rate of reendothelialization of denuded jugular vein from rabbits [30]. In addition, CNP gene transfer in rat aortic or carotid smooth muscle prevents smooth muscle cell proliferation and neointimal formation [31, 32]. While gene transfer may not be entirely practical under surgical conditions, it has been applied via an infiltrator angioplasty balloon catheter in a pig coronary balloon injury model [33]; stenosis and loss of cGMP levels were prevented at the site of CNP transfer. Therefore, the potential benefits of gene transfer of CNP in complementing surgery should be considered.

Comparative Relaxation
The reduced relative relaxant responses to acetylcholine in the vein compared with the artery in the present study are supported by observations of comparatively poor relaxation by ACh in SV compared with IMA [34]. Clearly, while ACh is an endogenous vasodilator, its use as a means of preventing vasospasm in SV conduits used for CABG would be limited.

The value of pretreatment of vascular conduits by papaverine is limited by its short duration of relaxing effects. The present study suggests that CNP is a more potent vasodilator than papaverine. Although it was not possible to calculate pEC50 for CNP or papaverine, where concentration response curves to CNP overlapped with that for papaverine there was a greater relaxation to CNP.

Stability of CNP In Vitro
The absence of any modulating effect on CNP-induced vasorelaxation by aprotinin suggests that biologically significant proteolytic breakdown of CNP by local enzymes does not occur in vitro. However, this does not preclude the possibility that such breakdown might occur in situ, especially with respect to CNP associated with the vessel wall rather than in circulation, or that breakdown of CNP might occur by enzymes unaffected by aprotinin, which is a nonspecific antagonist of neutral endopeptidases. Nor does this study consider long-term effects of neutral endopeptidases on the breakdown of CNP; it is likely that the brief duration of the experiments did not allow significant metabolism of the exogenous CNP.

Conclusions
In summary, this study demonstrates the ability of C-type natriuretic peptide to reverse endothelin-induced constriction of artery and vein grafts from patients undergoing CABG. This signals the therapeutic potential of using CNP as an antagonist of graft vasospasm after CABG.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
References
 
We are grateful to the surgeons of Harefield Hospital Cardiac Theatre for providing the human vascular tissue used in this study. This study was supported by the British Heart Foundation (PG2001058) and the Magdi Yacoub Institute.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Pompilio G, Rossoni G, Alamanni F, et al. Comparison of endothelium-dependent vasoactivity of internal mammary arteries from hypertensive, hypercholesterolemic, and diabetic patients Ann Thorac Surg 2001;72:1290-1297.[Abstract/Free Full Text]
  2. Downing SW, Edmunds LH. Release of vasoactive substances during cardiopulmonary bypass Ann Thorac Surg 1992;54:1236-1243.[Abstract]
  3. Drossos GE, Toumpoulis IK, Katritsis DG, et al. Is vitamin C superior to diltiazem for radial artery vasodilation in patients awaiting coronary artery bypass grafting? J Thorac Cardiovasc Surg 2003;125:330-335.[Abstract/Free Full Text]
  4. Myers MG, Fremes SE. Prevention of radial artery graft spasma survey of Canadian surgical centres. Can J Cardiol 2003;19:677-681.[Medline]
  5. Nussmeier NA, Slogoff S. Verapamil treatment of intraoperative coronary artery spasm Anesthesiology 1985;62:539-541.[Medline]
  6. Harvey WR, Monk CR. A study of the combined haemodynamic effects of dobutamine and enoximone in patients taking beta adrenoceptor antagonists Anaesth Intensive Care 1995;23:673-677.[Medline]
  7. Harrison WE, Mellor AJ, Clark J, Singer DR. Comparison of effects of phenoxybenzamine vs papaverine on norepinephrine-induced contraction in vitro Eur Heart J 2001;22:2209-2216.[Abstract/Free Full Text]
  8. Schmitt M, Cockcroft JR, Frenneaux MP. Modulation of the natriuretic peptide system in heart failurefrom bench to bedside?. Clin Sci 2003;105:141-160.[Medline]
  9. He G-W, Yang C-Q, Starr A. Overview of the nature of vasoconstriction in arterial grafts for coronary operations Ann Thorac Surg 1995;59:676-683.[Abstract/Free Full Text]
  10. Maguire JJ, Davenport AP. PD156707a potent antagonist of endothelin-1 in human diseased coronary arteries and vein grafts. J Cardiovasc Pharm 1998;31(suppl)S239–240.
  11. He G-W, Yang C-Q. Radial artery has higher receptor-mediated contractility but similar endothelial function compared with mammary artery Ann Thorac Surg 1997;63:1346-1352.[Abstract/Free Full Text]
  12. Carlucci F, Tabucchi A, Biagioli B, et al. Cardiac surgerymyocardial energy balance, antioxidant status and endothelial function after ischaemia-reperfusion. Biomed Pharmacother 2002;56:483-491.[Medline]
  13. Roth-Isigkeit A, Dibblet L, Eichler W, Schumacher J, Schmucker P. Blood levels of atrial natriuretic peptide, endothelin, cortisol and ACTH in patients undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass J Endocrinol Invest 2001;24:777-785.[Medline]
  14. Matheis G, Haak T, Beyersdorf F, Baretti R, Polywka C, Winkelmann BR. Circulating endothelin in patients undergoing coronary artery bypass grafting Eur J Cardiothorac Surg 1995;9:269-274.[Abstract]
  15. Göbel H, Ihling C, Dentz J, Schaefer HE, Zeiher AM, Fraedrich G. Increased tissue endothelin-1 like immunoreactivity in the internal mammary artery of patients with diabetes or hypercholesterolemia modulates the graft flow in the peri-operative period Eur J Cardiothorac Surg 1998;14:367-372.[Medline]
  16. Verma S, Maitland A, Weisel RD, et al. Increased endothelin-1 production in diabetic patients after cardioplegic arrest and reperfusion impairs coronary vascular reactivityreversal by means of endothelin antagonism. J Thorac Cardiovasc Surg 2002;123:1031-1034.[Free Full Text]
  17. Brody JI, Capuzzi DM, Fink GB. In situ endothelin in coronary artery disease Angiology 1996;47:1027-1032.
  18. Yang ZH, Richard V, von Segesser L, et al. Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteriesa new mechanism of vasospasm?. Circulation 1990;82:188-195.[Abstract/Free Full Text]
  19. Chester AH, Allen SP, Tadjkarimi S, Yacoub MH. Interaction between thromboxane A2 and 5-hydroxytryptamine receptor subtypes in human coronary arteries Circulation 1993;87:874-880.[Abstract/Free Full Text]
  20. Wiley KE, Davenport AP. Physiological antagonism of endothelin-1 in human conductance and resistance coronary artery Br J Pharmacol 2001;133:568-574.[Medline]
  21. Protter AA, Wallace AM, Ferraris VA, Weishaar RE. Relaxant effect of human brain natriuretic peptide on human artery and vein tissue Am J Hypertens 1996;9:432-436.[Medline]
  22. Honing ML, Smits P, Morrison PJ, Burnett Jr JC, Rabelink TJ. C-type natriuretic peptide-induced vasodilation is dependent on hyperpolarization in human forearm resistance vessels Hypertension 2001;37:1179-1183.[Abstract/Free Full Text]
  23. Davidson NC, Barr CS, Struthers AD. C-type-natriuretic peptide. An endogenous inhibitor of vascular angiotensin-converting enzyme activity Circulation 1996;93:1155-1159.[Abstract/Free Full Text]
  24. Nakamura M, Arakawa N, Yoshida H, Makita S, Hiramori K. Vasodilatory effects of C-type natriuretic peptide on forearm resistance vessels are distinct from those of atrial natriuretic peptide in chronic heart failure Circulation 1994;90:1210-1214.[Abstract/Free Full Text]
  25. Stingo AJ, Clavell AL, Heublein DM, et al. Presence of C-type natriuretic peptide in cultured human endothelial cells and plasma Am J Physiol Heart Circ Physiol 1992;263:1318-1321.
  26. Barton M, Beny JL, d'Uscio LV, et al. Endothelium-independent relaxation and hyperpolarization to C-type natriuretic peptide in porcine coronary arteries J Cardiovasc Pharmacol 1998;3:377-383.
  27. Banks M, Wei C-M, Kim CH, et al. Mechanism of relaxations to C-type natriuretic peptide in veins Am J Physiol Heart Circ Physiol 1996;271:1907-1911.
  28. Hobbs A, Foster P, Prescott C, et al. Natriuretic peptide receptor-C regulates coronary blood flow and prevents myocardial ischemia/reperfusion injurynovel cardioprotective role for endothelium-derived C-type natriuretic peptide. Circulation 2004;110:1231-1235.[Abstract/Free Full Text]
  29. Yamahara K, Itoh H, Chun TH, et al. Significance and therapeutic potential of the natriuretic peptides/cGMP/cGMP-dependent protein kinase pathway in vascular regeneration Proc Natl Acad Sci USA 2003;100:3404-3409.[Abstract/Free Full Text]
  30. Ohno N, Itoh H, Ikeda T, et al. Accelerated reendothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide Circulation 2002;105:1623-1626.[Abstract/Free Full Text]
  31. Doi K, Itoh H, Ikeda T, et al. Adenovirus-mediated gene transfer of C-type natriuretic peptide causes G1 growth inhibition of cultured vascular smooth muscle cells Biochem Biophys Res Commun 1997;239:889-894.[Medline]
  32. Ueno H, Haruno A, Morisaki N, et al. Local expression of C-type natriuretic peptide markedly suppresses neointimal formation in rat injured arteries through an autocrine/paracrine loop Circulation 1997;96:2272-2279.[Abstract/Free Full Text]
  33. Morishige K, Shimokawa H, Yamawaki T, et al. Local adenovirus-mediated transfer of C-type natriuretic peptide suppresses vascular remodeling in porcine coronary arteries in vivo J Am Coll Cardiol 2000;35:1040-1047.[Abstract/Free Full Text]
  34. Costello KB, Stewart DJ, Baffour R. Endothelin is a potent constrictor of human vessels used in coronary revascularization surgery Eur J Pharmacol 1990;186:311-314.[Medline]



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
S. Attaran, L. John, and A. El-Gamel
Clinical and Potential Use of Pharmacological Agents to Reduce Radial Artery Spasm in Coronary Artery Surgery
Ann. Thorac. Surg., April 1, 2008; 85(4): 1483 - 1489.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
H. Morawietz, S. Erbs, J. Holtz, A. Schubert, M. Krekler, W. Goettsch, O. Kuss, V. Adams, K. Lenk, F. W. Mohr, et al.
Endothelial Protection, AT1 Blockade and Cholesterol-Dependent Oxidative Stress: The EPAS Trial
Circulation, July 4, 2006; 114(1_suppl): I-296 - I-301.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
G. Pompilio and L. Sironi
Invited commentary
Ann. Thorac. Surg., October 1, 2005; 80(4): 1351 - 1352.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Mohammed Amrani
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kelsall, C. J.
Right arrow Articles by Singer, D. R.J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kelsall, C. J.
Right arrow Articles by Singer, D. R.J.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS