Cardiac transplantation and resistance artery myogenic tone

2004 ◽  
Vol 82 (10) ◽  
pp. 840-848 ◽  
Author(s):  
Farzad Moien-Afshari ◽  
Peter L Skarsgard ◽  
Bruce M McManus ◽  
Ismail Laher
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Contractile Function ◽  
Myogenic Tone ◽  
Resistance Arteries ◽  
Interstitial Edema ◽  
Functional Changes ◽  
Ventricular Compliance ◽  
Myogenic Regulation ◽  
Oxide Synthase

Transplantation is an effective treatment for end-stage heart disease; however, most grafts eventually fail by progressive cardiac failure. Primarily, failure is ischemic due to the occlusive nature of transplant vascular disease (TVD). Early after transplantation and preceding TVD, alterations in coronary physiology such as reduced vascular myogenic tone occur. Resistance arteries possess an inherent ability to constrict in response to transmural pressure; this constrictive response (myogenic tone) is important in fluid homeostasis. Recent evidence suggests that a decline in myogenic tone leads to deficits in cardiac contractility. Factors that reduce myogenic tone in transplantation include constitutive nitric oxide synthase and inducible nitric oxide synthase catalyzed, NO-mediated vasodilation as well as deficits in arterial contractile function. Reduced myogenic tone in allograft resistance arteries increases coronary blood flow such that hydrostatic pressure surpasses oncotic pressure, causing cardiac interstitial edema. This generalized edema decreases ventricular compliance leading to heart failure during the course of acute immune rejection of the graft. Cyclosporine A treatment reduces immune mediated dysregulation of myogenic tone, resulting in reduced interstitial edema and improved cardiac function. In this review, we discuss aspects of TVD and myogenic tone signaling mechanisms and how aberrations in myogenic regulation of arterial tone contribute to functional changes observed in cardiac transplant.Key words: myogenic tone, smooth muscle, nitric oxide, transplantation, edema.

Endothelin-1 ameliorates contractile depression by lipopolysaccharide in cardiac myocytes

1997 ◽  
Vol 273 (3) ◽  
pp. H1403-H1407 ◽  
Author(s):  
S. Yasuda ◽  
W. Y. Lew
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cardiac Myocytes ◽  
Contractile Function ◽  
Adult Rabbit ◽  
Nitric Oxide Synthase Inhibitor ◽  
Endothelin 1 ◽  
Cardiac Depression ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Lipopolysaccharide (LPS) induces cardiac depression by activating nitric oxide pathways to increase guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of nitric oxide. Endothelin-1 (ET-1) may interact with nitric oxide pathways. We hypothesized that ET-1 modulates LPS-induced contractile depression in cardiac myocytes. Adult rabbit cardiac myocytes exposed to LPS (10 ng/ml) developed decreased cell shortening after 6 h, with an increase in cardiac cGMP levels [606 +/- 36 (SE) fmol/mg protein] compared with control myocytes (360 +/- 26 fmol/mg protein, P < 0.05). LPS effects were completely blocked by coincubation with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (1 mM). Coincubation with ET-1 (10 nM) attenuated the contractile depression and increase in cGMP with LPS (482 +/- 28 fmol/mg protein, P < 0.05 vs. LPS alone). ET-1 alone did not alter cGMP levels (350 +/- 30 fmol/mg protein). ET-1 effects on contractile function were blocked by BQ-123 (10 microM), a selective ET-1 type A receptor antagonist. We conclude that ET-1 ameliorates LPS-induced contractile depression in cardiac myocytes by attenuating LPS effects on nitric oxide-cGMP pathways.

PKC mediates LPS- and phorbol-induced cardiac cell nitric oxide synthase activity and hypocontractility

1995 ◽  
Vol 269 (6) ◽  
pp. H1891-H1898 ◽  
Author(s):  
T. M. McKenna ◽  
S. Li ◽  
S. Tao
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cardiac Myocyte ◽  
Contractile Function ◽  
Dependent Manner ◽  
Cardiac Cell ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Myocyte Contractility ◽  
Rat Cardiac Myocytes

Lipopolysaccharide (LPS) treatment impairs cardiac myocyte contractility in a nitric oxide synthase (NOS)-dependent manner. The objective of this study was to assess whether protein kinase C (PKC) transduces the LPS signal into an enhanced NOS activity in rat cardiac myocytes. LPS (100 ng/ml) stimulated myocyte PKC activity, inducible NOS (iNOS) expression, and NOS activity in a time- and protein synthesis-dependent fashion. Directly activating PKC with beta-phorbol 12,13-dibutyrate (beta-PDB) also induced myocyte iNOS synthesis and NOS activity and reduced electrically stimulated contractility, while the inactive alpha-PDB was ineffectual. Contractility could be restored to beta-PDB-incubated cells by superfusion with the NOS inhibitor N omega-nitro-L-arginine methyl ester. PKC blockade with sphingosine, chelerythrine, or calphostin-C precluded LPS- and beta-PDB-induced increases in NOS activity and protected contractility. Depletion of PKC by 18 h of incubation with beta-PDB in the presence of chelerythrine also blocked acquisition of enhanced NOS activity and contractile dysfunction when the myocytes were subsequently exposed to LPS. These findings suggest that PKC is a significant intracellular mediator for the effects of LPS on cardiac cell NOS activity and contractile function.

Role of Neuronal Nitric Oxide Synthase in Modulating Microvascular and Contractile Function in Rat Skeletal Muscle

2011 ◽  
Vol 18 (6) ◽  
pp. 501-511 ◽  
Author(s):  
STEVEN W. COPP ◽  
DANIEL M. HIRAI ◽  
SCOTT K. FERGUSON ◽  
TIMOTHY I. MUSCH ◽  
DAVID C. POOLE
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Nitric Oxide Synthase ◽  
Contractile Function ◽  
Neuronal Nitric Oxide Synthase ◽  
Rat Skeletal Muscle ◽  
Oxide Synthase

l-NAME, a nitric oxide synthase inhibitor, diminishes oxidative damage in urinary bladder partial outlet obstruction

2006 ◽  
Vol 290 (2) ◽  
pp. F357-F363 ◽  
Author(s):  
William Conners ◽  
Catherine Whitebeck ◽  
Paul Chicester ◽  
Robert Legget ◽  
Alpha Dian-Yu Lin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Contractile Function ◽  
Outlet Obstruction ◽  
Cellular Damage ◽  
Ischemia And Reperfusion Injury ◽  
Free Radical Damage ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Partial bladder outlet obstruction (PBOO) results in cellular damage due to ischemia and reperfusion injury. Our study seeks to establish how early this damage can occur and the role that nitric oxide may play in its pathophysiology. Surgical PBOO (1, 3, and 7 days) were performed on male New Zealand White rabbits. Half of the animals were premedicated for 3 days with NG-nitro-l-arginine methyl ester(l-NAME), an inhibitor of nitric oxide synthase before obstruction. Bladder weight increased with duration of PBOO but was significantly lower at 3 and 7 days in animals treated with l-NAME compared with their untreated counterparts. Contractile function decreased progressively with PBOO duration. At 1 day postobstruction, bladder contractility was significantly lower in the l-NAME rabbits than in the untreated rabbits. At 3 and 7 days, contractility of the l-NAME bladders was equal or higher than the untreated bladders. The level of hypoxia at 1 day after obstruction was significantly higher in the l-NAME-treated animals than in the untreated controls but equal at 3 and 7 days obstruction. Increased nitrotyrosine was seen by Western blot in all obstructed animals. However, the amount was significantly less in the l-NAME-treated animals at 3 and especially at 7 days. Nerve density decreased progressively after obstruction; however, it decreased to a significantly lesser degree in the l-NAME-treated bladders than in the untreated groups. These results suggest that l-NAME pretreatment enhanced ischemic damage at 1 day after obstruction but protected the bladder from nitric oxide-generated free radical damage at the later time periods by inhibiting the generation of nitrotyrosine.

scholarly journals Displacement-encoded and manganese-enhanced cardiac MRI reveal that nNOS, not eNOS, plays a dominant role in modulating contraction and calcium influx in the mammalian heart

2012 ◽  
Vol 302 (2) ◽  
pp. H412-H419 ◽  
Author(s):  
Moriel H. Vandsburger ◽  
Brent A. French ◽  
Christopher M. Kramer ◽  
Xiaodong Zhong ◽  
Frederick H. Epstein
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cardiac Mri ◽  
Calcium Influx ◽  
Contractile Function ◽  
Dominant Role ◽  
Contractile Reserve ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Within cardiomyocytes, endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) are thought to modulate L-type calcium channel (LTCC) function and sarcoplasmic reticulum calcium cycling, respectively. However, divergent results from mostly invasive prior studies suggest more complex roles. To elucidate the roles of nNOS and eNOS in vivo, we applied noninvasive cardiac MRI to study wild-type (WT), eNOS−/−, and nNOS−/− mice. An in vivo index of LTCC flux (LTCCI) was measured at baseline (Bsl), dobutamine (Dob), and dobutamine + carbacholamine (Dob + CCh) using manganese-enhanced MRI. Displacement-encoded MRI assessed contractile function by measuring circumferential strain (Ecc) and systolic (dEcc/dt) and diastolic (dEcc/dtdiastolic) strain rates at Bsl, Dob, and Dob + CCh. Bsl LTCCI was highest in nNOS−/− mice ( P < 0.05 vs. WT and eNOS−/−) and increased only in WT and eNOS−/− mice with Dob ( P < 0.05 vs. Bsl). LTCCI decreased significantly from Dob levels with Dob + CCh in all mice. Contractile function, as assessed by Ecc, was similar in all mice at Bsl. With Dob, Ecc increased significantly in WT and eNOS−/− but not nNOS−/− mice ( P < 0.05 vs. WT and eNOS−/−). With Dob + CCh, Ecc returned to baseline levels in all mice. Systolic blood pressure, measured via tail plethysmography, was highest in eNOS−/− mice ( P < 0.05 vs. WT and nNOS−/−). Mice deficient in nNOS demonstrate increased Bsl LTCC function and an attenuated contractile reserve to Dob, whereas eNOS−/− mice demonstrate normal LTCC and contractile function under all conditions. These results suggest that nNOS, not eNOS, plays the dominant role in modulating Ca2+ cycling in the heart.

Sign in / Sign up

Export Citation Format

Share Document