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S U Sys

Publications and source records attributed to S U Sys.

At least 37 records · Page 2Linked to original sources
PubMed1998

Ca2+ channel-blocking activity of propranolol and betaxolol in isolated bovine retinal microartery.

The relaxant action of the standard beta-blocker propranolol was compared with betaxolol, a beta-blocker with established vasorelaxant properties. Ring segments of bovine retinal microartery (n=36, theta=237 microm), which lacks adrenergic nerves and beta-adrenoceptors, were mounted in an organ bath for isometric force recording. l-, d-, dl-Propranolol and betaxolol were equally effective in relaxing tonic K+-induced contractions. The median effective dose (ED50) value was approximately 10(-5) M for both beta-blockers. The relaxation by both beta-blockers was unaffected by endothelium removal. Like verapamil, both beta-blockers induced smaller relaxation of tonic prostaglandin F2alpha (PGF2alpha)-induced force, which depended less on Ca2+ influx than did K+-induced force: K+-, but not PGF2alpha-induced contractions were abolished in Ca2+-free medium. The minor betaxolol-induced relaxation of tonic PGF2alpha-induced force was blocked in Ca2+-free medium. With repeated exposures to PGF2alpha in Ca2+-free medium, initial phasic PGF2alpha-induced force declined less with every exposure than did subsequent tonic force. When the preparations were briefly equilibrated with K+- and Ca2+-rich solution before every exposure to PGF2alpha phasic force did not decline, indicating that phasic force primarily depended on Ca2+ released from intracellular stores. Both beta-blockers failed to relax phasic PGF2alpha-induced force. Thus propranolol and betaxolol are equipotent vasorelaxant drugs in retinal microartery, both probably acting via Ca2+ channel blockade. This activity (that shows no stereospecificity) thus appears to be a more general property of beta-blockers. Microarteries might be more sensitive to this activity than are conductance arteries.

Adrenergic beta-Antagonists↗
PubMed1998

Vascular endothelial dysfunction contributes to myocardial depression in ischemia-reperfusion in the rat.

Endocardial and vascular myocardial capillary endothelium has been shown to modulate the contractile characteristics of myocardium by altering myofibrillar affinity for calcium. Although the release of endothelial-derived substances that modify myocardial contractility has been shown to be altered in certain physiologic and pathologic situations, until now no study has evaluated whether the direct modulatory effects of endothelium on its subjacent myocardium were altered in pathologic situations and contributed to loss of contractile function. This study was designed to evaluate whether the direct contractile modulatory effects of endocardial and (or) vascular endothelium were altered and whether these alterations contributed to contractile dysfunction in a model of ischemia-reperfusion. Sixty-two perfused rat hearts as Langendorff preparations were randomized to no intervention, intracoronary Triton X100 injection (to render vascular endothelium dysfunctional), ischemia (30 min)-reperfusion (20 min), and ischemia-reperfusion followed by intracoronary Triton X100 injection. Coronary endothelial-dependent vascular reactivity and vascular smooth muscle reactivity were assessed by serotonin and sodium nitroprusside, respectively. Myocardial damage was assessed by coronary effluent creatine phosphokinase and by morphologic studies. Papillary muscles were then excised and contractile characteristics evaluated at varying extracellular calcium concentration prior to and after endocardial endothelial removal with Triton X100. All three interventions eliminated all coronary vascular response to serotonin but did not modify response to nitroprusside. Creatine phosphokinase values rose only in hearts with ischemia-reperfusion, and only minor morphologic changes occurred, mostly in hearts with ischemia-reperfusion. Papillary muscles from hearts with intracoronary Triton X100 injection had lower contractile indices compared with normal controls (total tension 4.0 vs. 4.6 g/mm2, p < 0.01) and an abbreviation of contraction duration. Increasing extracellular calcium concentration from to 0.7 to 3.25 mM eliminated these differences. Similar but more marked decreases in contractile indices and twitch duration were noted in the two ischemia-reperfusion groups, but consistent with some myocardial damage being present, increasing extracellular calcium concentration to 3.25 or 7 mM did not fully eliminate these differences. In both ischemia-reperfusion groups and the intracoronary Triton X100 group, the relative increase in total tension with increasing extracellular calcium concentrations was similar (35 to 38%) and greater than that of the control group (25%), consistent with dysfunction of vascular endothelium contributing to myocardial dysfunction in the three intervention groups. Endocardial endothelial removal had a similar effect in all four groups, suggesting that dysfunction of endocardial endothelium does not play a role in this model. We conclude that vascular but not endocardial endothelial dysfunction contributes to the myocardial dysfunction that occurs during ischemia-reperfusion injury.

Animals↗
PubMed1997

Aminoguanidine reverses aortic hyporeactivity to noradrenaline in portal vein-ligated rats.

To evaluate the role of the inducible and endothelial constitutive nitric oxide synthase in vascular hyporeactivity to vasopressors in portal hypertension, in vitro experiments were performed on intact and endothelium-denuded isolated thoracic aortic rings from portal vein-ligated and sham-operated rats in control conditions, in the presence of aminoguanidine alone, considered to be a selective inhibitor of the inducible nitric oxide synthase, and of aminoguanidine and the nonselective nitric oxide synthase inhibitor N(G)-nitro-L-arginine. In control conditions, hyporeactivity to noradrenaline was observed in both rings with and without endothelium from portal hypertensive versus sham-operated rats. In the rings with endothelium, aminoguanidine reverted this hyporeactivity in portal hypertensive rats. N(G)-Nitro-L-arginine caused an additional shift to the left of the concentration-response curves to noradrenaline in portal hypertensive and a similar shift in sham-operated rats. In the endothelium-denuded rings, aminoguanidine caused no significant changes in portal hypertensive rats, whereas a significant shift to the right in the sham-operated rats was noted, however similar as the shift in the time controls not preincubated with aminoguanidine. No significant further changes were observed after preincubation with the two inhibitors. The endothelium-dependent relaxations to acetylcholine were attenuated in portal hypertensive versus sham-operated rats; addition of aminoguanidine shifted the relaxation curves to the left in portal hypertensive but not in sham-operated rats. These results provide indirect evidence for an increased activity of the inducible nitric oxide synthase in the intact aortic rings but not in the endothelium-denuded rings from portal vein-ligated rats, where other factors seem to be responsible for the observed hyporeactivity to noradrenaline. The endothelial constitutive nitric oxide synthase in rings from portal vein-ligated rats shows a reduced activity which is alleviated after inhibition of the inducible enzyme by aminoguanidine.

Acetylcholine↗
PubMed1997

K+ and Cl- contribute to resting membrane conductance of cultured porcine endocardial endothelial cells.

The conventional whole cell patch-clamp technique was used to measure the resting membrane conductance and membrane currents of single, nonstimulated, cultured endocardial endothelial cells of the porcine right ventricle in different ionic conditions. All cells displayed the barium-sensitive, inwardly rectifying potassium (K+) current (I(Ki)). In 65% of the cells, I(Ki) was the predominant membrane current. The mean zero-current potential (V0) was -61.0 +/- 12.5 mV (+/- SD, n = 45). In 35% of the cells, I(Ki) was superposed on an outwardly rectifying (OR) current. V0 of these cells was more depolarized (-33.5 +/- 22.0 mV, n = 26). High intracellular Cl- (122 instead of 52 mmol/l) activated or increased the OR current and shifted V0 in the direction of the equilibrium potential for Cl-. In cells displaying the OR current, V0 was dependent on extracellular Cl-, indicating the contribution of an OR Cl- current in setting V0. At low intracellular Cl- (6 instead of 52 mmol/l), the OR current was decreased and V0 shifted in the direction of the equilibrium potential for K+. In cells not displaying the OR current, V0 was dependent on extracellular K+ but not on Cl-, indicating major permeability to K+ in these conditions. Block of the OR current by the Cl(-)-channel blockers anthracene-9-carboxylic acid (1 mmol/l), flufenamic acid (100-500 micromol/l), and Zn2+ (100-200 micromol/l) provided further evidence for the anionic nature of the OR current. After inhibition of I(Ki) and the OR Cl- current, a third current component was observed in 50% of the cells. The pharmacology and voltage dependence of this current suggested the presence of Ca2+-activated K+ channels in endocardial endothelial cells. We concluded that the resting membrane conductance of nonstimulated endocardial endothelial cells is mainly determined by the combined activity of inwardly rectifying K+, OR Cl-, and Ca2+-activated K+ channels.

Animals↗
PubMed1997

Endocardial endothelium in the avascular heart of the frog: morphology and role of nitric oxide.

Endocardial endothelial morphology and the physiological modulatory role of nitric oxide (NO) were studied in an in vitro preparation of the working intact heart of the frog Rana esculenta, which lacks coronary vasculature and is thus devoid of a coronary vascular endothelium. En face confocal scanning laser microscopy of samples of perfused fixed hearts demonstrated the presence of NO synthase as a cytoplasmic constituent of the endocardial endothelial cells. Stroke volume (as a measure of performance in paced frog hearts) and stroke work (as an index of systolic function) increased by approximately 5 % after inhibition of the NO-cGMP pathway with 10(-4 )mol l-1 NG-nitro-l-arginine methyl ester and by approximately 8 % after inhibition with 10(-6 )mol l-1 Methylene Blue. In contrast, stroke volume and stroke work decreased by approximately 22 % after activation of the NO-cGMP pathway with sodium nitroprusside (10(-4 )mol l-1), while 3-morpholinosydnonimine (5x10(-8) to 10(-5 )mol l-1) caused a decrease of between 15 and 30 % and 8-bromo-cGMP (10(-6 )mol l-1) a decrease of approximately 8 %. These responses were significantly attenuated after exposure of the ventricular luminal to Triton X-100 (0.05 %, 0.1 ml), which itself increased performance (by over 10 %) without detectable morphological changes. These results show that the endocardial endothelium of Rana esculenta produces amounts of NO sufficient to modulate ventricular performance.

Animals↗
PubMed1996

Simultaneous coronary pressure and flow velocity measurements in humans. Feasibility, reproducibility, and hemodynamic dependence of coronary flow velocity reserve, hyperemic flow versus pressure slope index, and fractional flow reserve.

BACKGROUND: To assess coronary lesion severity in the catheterization laboratory, several guide wire-based methods have been proposed. The purpose of the present study was to compare the feasibility and the reproducibility of coronary flow velocity reserve (CFVR), instantaneous hyperemic diastolic velocity-pressure slope index (IHDVPS), and pressure-derived myocardial fractional flow reserve (FFRmyo). METHODS AND RESULTS: From distal coronary pressure and flow velocity signals (0.014-in guide wires), CFVR, IHDVPS, and FFRmyo were computed in 15 stenoses (13 patients) under the four following pairs of conditions: (1) twice under baseline conditions; (2) during atrial pacing at 80 and 110 bpm; (3) before and during intravenous infusion of nitroprusside; and (4) before and during intravenous infusion of dobutamine. A total of 104 measurements were obtained. Both CFVR and FFRmyo could be calculated in all cases. IHDVPS could be calculated in only 79% of cases. The mean value of CFVR did not change between the two baseline measurements and during infusion of nitroprusside but decreased from 1.85 +/- 0.41 to 1.66 +/- 0.45 (P < .05) during atrial pacing and from 1.90 +/- 0.50 to 1.41 +/- 0.28 (P < .05) during dobutamine infusion. The mean values of IHDVPS and FFRmyo remained similar, whichever the changes in hemodynamic conditions. The coefficient of variation between two consecutive measurements was significantly lower for FFRmyo (4.2%) than for CFVR (17.7%) and for IHDVPS (24.7%). CONCLUSIONS: CFVR is easy to measure but sensitive to hemodynamic changes. IHDVPS can be measured only in < 80% of cases and is highly variable even without changes in hemodynamic conditions. FFRmyo is easy to measure and almost independent of hemodynamic changes.

Aged↗
PubMed1996

Myocardial contractile response to nitric oxide and cGMP.

BACKGROUND: Cardiac endothelium releases a number of factors that may modulate performance of underlying cardiac muscle. Nitric oxide (NO), which accounts for the biological activity of the vascular endothelium-derived relaxing factor and relaxes vascular smooth muscle by elevating intracellular cGMP, may be involved in this cardiac modulation. METHODS AND RESULTS: We examined the myocardial contractile effects of the NO-releasing nitrovasodilators sodium nitroprusside (SNP), 3-morpholino-sydnonimine (SIN-1), and S-nitroso-N-acetyl-penicillamine (SNAP); of a cGMP analogue, 8-bromo-cGMP; and of the cGMP-phosphodiesterase inhibitor zaprinast in isolated cat papillary muscle. Modulation of these effects by endocardial endothelium (EE) and by cholinergic and adrenergic stimulation was also investigated. Concentration-response curves with addition of NO-releasing nitrovasodilators (SNP, SIN-1, SNAP) and 8-bromo-cGMP resulted in a biphasic inotropic response. Although administration of low concentrations induced a positive inotropic effect, higher concentrations induced a negative inotropic effect. Both NO-induced positive and negative inotropic effects were attenuated by methylene blue, suggesting a role for cGMP. The response to high concentrations of 8-bromo-cGMP was shifted to the right in muscles with damaged EE, whereas cholinergic stimulation shifted the curve leftward. Zaprinast caused a monophasic concentration-dependent positive inotropic effect; damaging the EE shifted the terminal portion of the curve upward. Concomitant cholinergic or adrenergic stimulation modified the response to zaprinast into a negative inotropic response. CONCLUSIONS: NO and cGMP induced a concentration-dependent biphasic contractile response. The myocardial contractile effects of NO and cGMP were modulated by the status of EE and by concomitant cholinergic or adrenergic stimulation.

Animals↗
PubMed1996

Personality as independent predictor of long-term mortality in patients with coronary heart disease.

BACKGROUND: Emotional distress has been related to mortality in patients with coronary heart disease (CHD), but little is known about the role of personality in long-term prognosis. We postulated that type-D personality (the tendency to suppress emotional distress) was a predictor of long-term mortality in CHD, independently of established biomedical risk factors. METHODS: We studied 268 men and 35 women with angiographically documented CHD, aged 31-79 years, who were taking part in an outpatient rehabilitation programme. All patients completed personality questionnaire at entry to the programme. We contacted them 6-10 years later (mean 7-9) to find out survival status. The main endpoint was death from all causes. FINDINGS: At follow-up, 38 patients had died; there were 24 cardiac deaths. The rate of death was higher for type-D patients than for those without type-D (23 [27%]/85 vs 15 [7%]/218; p < 0.00001). The association between type-D personality and mortality was still evident more than 5 years after the coronary event and was found in both men and women. Mortality was also associated with impaired left ventricular function, three-vessel disease, low exercise tolerance, and the lack of thrombolytic therapy after myocardial infarction. When we controlled for these biomedical predictors in multiple logistic regression analysis, the impact of type-D remained significant (odds ratio 4.1 [95% CI 1.9-8.8]; p = 0.0004). In this group of CHD patients, type-D was an independent predictor of both cardiac and non-cardiac mortality. Social alienation and depression were also related to mortality, but did not add to the predictive power of type-D. INTERPRETATION: We found that type-D personality was a significant predictor of long-term mortality in patients with established CHD, independently of biomedical risk factors. Personality traits should be taken into account in the association between emotional distress and mortality in CHD.

Adult↗
PubMed1996

Abnormal systolic intraventricular flow velocities after valve replacement for aortic stenosis. Mechanisms, predictive factors, and prognostic significance.

BACKGROUND: Dynamic intraventricular flow velocities after valve replacement for aortic stenosis have been associated with high in-hospital morbidity and mortality. The aims of the present study were to determine the mechanisms and preoperative predictors of abnormal flow velocity (AFV) after valve replacement for aortic stenosis and to assess the clinical course of patients with AFV after surgery. METHODS AND RESULTS: One hundred consecutive patients with pure aortic stenosis were studied prospectively before operation by cardiac catheterization and Doppler echocardiography. After surgery, intraventricular flow was studied by Doppler echocardiography at rest, during nipride infusion, and during dobutamine infusion. AFV (defined as a systolic dagger-shaped Doppler spectrum > 2 m/s) occurred in 14 patients at rest and in 27 patients during nipride and/or dobutamine infusion. In most patients, AFV was associated with left ventricular cavity squeezing. Left ventricular end-diastolic diameter, preoperative intraventricular flow velocity and septal-to-posterior wall thickness ratio by Doppler echocardiography, and mean transvalvular pressure gradient and ejection fraction by catheterization emerged as predictors of resting postoperative AFV. Patients with resting AFV had a higher incidence of dyspnea or hypotension (64% versus 21%, P < .01) and a longer hospital stay (13.1 +/- 5.8 versus 11.1 +/- 2.5, P < .05) than patients without AFV. In contrast, at a 1-year follow-up, no patient with resting AFV died. CONCLUSIONS: First, AFV occurs in 14% of patients at rest after valve replacement for aortic stenosis and can be provoked or worsened by ventricular unloading or inotropic stimulation. Second, AFV is related more frequently to cavity squeezing than to systolic anterior motion of the mitral valve apparatus. Third, a typical pattern (small, hyperdynamic, and asymmetrically hypertrophied ventricle) is predictive for postoperative AFV and should be taken into account for the postoperative management. Finally, the presence of AFV at rest is associated with high in-hospital morbidity but good long-term prognosis.

Adult↗
PubMed1996

Dobutamine-induced wall motion abnormalities: correlations with myocardial fractional flow reserve and quantitative coronary angiography.

OBJECTIVES: This study evaluated both the relation between dobutamine-induced wall motion abnormalities and the physiologic and morphologic features of epicardial coronary artery stenoses and the impact of the extent of the area at risk on the sensitivity of dobutamine echocardiography. BACKGROUND: The accuracy of dobutamine echocardiography has traditionally been assessed by comparing results with stenosis geometry. Myocardial fractional flow reserve is a functional index of coronary stenosis severity that takes into account both antero-grade and collateral flow and may therefore be a more appropriate standard for comparison. METHODS: Seventy-five patients with normal left ventricular function, good echocardiographic images and an isolated coronary stenosis underwent, within 6 h, dobutamine echocardiography, quantitative coronary angiography and intracoronary pressure measurements. Myocardial fractional flow reserve was calculated as the ratio of mean hyperemic distal coronary to aortic pressure. RESULTS: The degree of dobutamine-induced dyssynergy correlated significantly with percent diameter stenosis (r = 0.68), area stenosis (r = 0.68) and minimal lumen diameter (r = -0.60) and markedly better with myocardial fractional flow reserve (r = -0.77). However, marked dispersion of the individual data was observed. The sensitivity of dobutamine echocardiography in detecting lesions with a minimal lumen diameter < or = 1 mm and diameter stenosis > or = 50% was 83% and 80%, respectively. All but one patient with a myocardial fractional flow reserve >0.75 had a normal stress test result. Among patients with a myocardial fractional flow reserve < or = 0.75, the sensitivity of dobutamine echocardiography was significantly lower for lesions in vessels with a reference diameter < or = 2.6 mm than for lesions in larger vessels (58% vs. 90%, p = 0.008). CONCLUSIONS: 1) The magnitude of wall motion abnormalities induced by dobutamine infusion correlates with angiographic and, more closely, with functional indexes of stenosis severity, even though a wide scatter is observed. 2) In patients with a functionally significant stenosis, the amount of myocardium at risk is a critical determinant of the accuracy of dobutamine echocardiography.

Coronary Angiography↗
PubMed1996

Endocardial endothelial dysfunction and heart failure.

Like vascular endothelium, the EE plays a role in transendothelial transport, in coagulant and thrombotic processes, and in interactions with inflammatory cells. In addition, EE is involved in the modulation of cardiac performance of subjacent myocardium. EE dysfunction includes insufficient as well as excessive performance of any of its multiple functions. Dysfunction can progress from a disturbed modulation of myocardial performance and an imbalance in the release of growth factors to changes in EE cytoskeletal organization, with concomitant changes in transendothelial permeability, and in extreme cases, to loss of endothelial integrity and frank denudation. Structural and functional impairment of EE and of endocardial interstitial cells may be primary or secondary to the disease. Mechanical stress, various hormones and cytokines can initiate EE dysfunction. EE dysfunction may influence the development of cardiac failure in endo(myo)cardial fibrosis (Loeffler's endocarditis and carcinoid syndrome) and in dilated cardiomyopathy. Although Bouillaud, in 1836, was referring to endocarditis when stating: (quote: see text) his statement may presently find a much broader field of applicability in cardiology.

Animals↗
PubMed1996

Role of the endocardial endothelium in the negative inotropic effects of thiopental.

BACKGROUND: Myocardial function is regulated by endocardial endothelium (EE). Several studies have demonstrated the involvement of vascular endothelium in regulating the vasoactive effects of anesthetic agents. Because vascular endothelium and EE form a contiguous layer, it was postulated that EE might also be involved in regulating the inotropic effects of anesthetics. The effects of thiopental on isolated feline papillary muscle with and without EE were examined. METHODS: The study was performed on isolated cat papillary muscles (n = 48). The effects of increasing doses of thiopental (1.5, 3, 6, 9, 12, and 24 micrograms/ml) on isometric and isotonic muscle contraction parameters were evaluated in three protocols under different experimental conditions. In the first protocol, the effects of thiopental were studied in the muscles with an intact EE (group A, n = 8) and muscles in which the EE was selectively damaged by a 1-s immersion in 0.5% Triton X-100 (group B, n = 8). In the second protocol, cumulative concentration responses for thiopental were obtained in muscles with (group C, n = 8) and without (group D, n = 8) EE, pretreated with 10(-3) M of the blocking NG-nitro-L-arginine methyl ester (L-NAME). In the third protocol, the same cumulative concentration responses were obtained for thiopental in muscles with (group E, n = 8) and without (group F, n = 8) EE after pretreatment with 5 x 10(-4) M L-arginine. RESULTS: In the presence of an intact EE, thiopental induced a dose-dependent decrease in myocardial function. With the EE removed, low doses of thiopental (1.5 to 6 micrograms/ml) no longer altered myocardial function. Pretreatment of the muscles with L-NAME inhibited the negative inotropic effects of low doses of thiopental and mimicked the response obtained after EE was removed. Pretreatment with L-arginine slightly accentuated the negative inotropic effects of low doses of thiopental. CONCLUSIONS: The negative inotropic actions of small doses of thiopental depend on the presence of an intact EE. Pretreatment of the muscles with L-NAME inhibited the negative inotropic effects of low doses of thiopental, suggesting possible involvement of the nitric oxide pathway.

Anesthetics, Intravenous↗
PubMed1995

Relation between myocardial fractional flow reserve calculated from coronary pressure measurements and exercise-induced myocardial ischemia.

BACKGROUND: Myocardial fractional flow reserve (FFRmyo) is a functional index of stenosis severity that can be derived from intracoronary pressure measurements performed during maximal vasodilatation. It is defined as the maximal myocardial perfusion during hyperemia in the presence of a stenosis in the epicardial artery expressed as a fraction of its normal maximal expected value. To determine threshold values of FFRmyo, of hyperemic translesional pressure gradient (delta P(max)), and of resting translesional pressure gradient (delta P(rest)) that are uniformly associated with exercise-induced ischemia, we studied the relation between these pressure-derived indexes and the results of exercise ECG. METHODS AND RESULTS: We studied 60 patients with an isolated lesion in one major epicardial coronary artery, normal left ventricular function, and no left ventricular hypertrophy. Maximal exercise ECG (off anti-ischemic medication) was performed within 6 hours before catheterization. Intracoronary pressure measurements were taken at rest and during hyperemia with a pressure monitoring guide wire. ST-segment depressions at peak exercise (considered abnormal when > or = 0.1 mV) were compared with FFRmyo, delta P(max), and delta P(rest). Thirty-seven patients had an abnormal and 23 patients a normal exercise ECG. A significant linear correlation was found between the magnitude of ST-segment depressions and both FFRmyo and delta P(max) (r = -.75, SEE = 0.53; r = .71, SEE = 0.56). A weaker correlation was noted between ST-segment depressions and delta P(rest) (r = .53, SEE = 0.67). Sensitivity and specificity curves were constructed for the prediction of an abnormal exercise ECG for the three pressure-derived indexes. The values that most accurately predicted an abnormal exercise ECG were 66% for FFRmyo, 31 mm Hg for delta P(max), and 12 mm Hg for delta P(rest). No patient with a FFRmyo value > 72% showed an abnormal exercise ECG. In addition, receiver operating characteristic curves demonstrated a greater accuracy of FFRmyo and of delta P(max) than of delta P(rest) for predicting the results of the exercise ECG. CONCLUSIONS: In the present study, cutoff values of FFRmyo and translesional pressure gradients are established from the relation between intracoronary pressure-derived indexes and ECG signs of myocardial ischemia during maximal exercise. These values can be helpful for clinical decision making in cases with dubious angiographic results. Furthermore, our data support the concept that stenosis physiology is better reflected by hyperemic than by basal measurements.

Adult↗
PubMed1995

Role of nitric oxide in hyporeactivity to noradrenaline of isolated aortic rings in portal hypertensive rats.

To test the hypothesis that induction of nitric oxide synthase causes systemic vascular hyporesponsiveness to vasopressors in portal hypertension, we performed in vitro experiments on isolated thoracic aortic rings from partial portal vein ligated or sham operated rats at 3 weeks postoperatively. The concentration-response curves to noradrenaline of intact and endothelium-denuded aortic rings from portal hypertensive rats were significantly shifted to the right as compared to those from sham operated animals. Maximal contractions did not significantly differ. Addition of NG-nitro-L-arginine, a specific inhibitor of nitric oxide synthase, shifted the curves to the left in both sham operated and portal hypertensive rats, so that in intact rings, the concentrations of noradrenaline producing half-maximal response did not significantly differ any more between sham operated and portal vein ligated rats. In endothelium-denuded rings, a hyporeactivity to noradrenaline persisted in portal vein ligated rats. Furthermore, NG-nitro-L-arginine induced an additional significant increase in the maximal response to noradrenaline in sham operated as compared to portal hypertensive rats. The endothelium-dependent relaxations to acetylcholine were attenuated in portal hypertensive rats as compared to sham operated animals. From these results, it can be concluded that increased nitric oxide production in the vascular wall of thoracic aorta of portal hypertensive rats is involved in their hyporesponsiveness to noradrenaline. Our findings in endothelium-denuded rings indicate the involvement of the inducible nitric oxide synthase in the smooth muscle layer. Involvement of an inducible nitric oxide synthase in the endothelium cannot be excluded. The endothelial constitutive nitric oxide synthase, however, seems to be suppressed in portal vein ligated rats.

Acetylcholine↗
PubMed1995

Mechanisms of endocardial endothelium modulation of myocardial performance.

The endocardial endothelium (EE) modulates the performance of the subjacent myocardium and plays an important role in regulation of cardiac function. This modulation has been confirmed in a number of different species and in both in vitro and in vivo conditions. The mechanisms of EE modulation of myocardial performance are still under investigation and the possibilities include the role of EE as a transendothelial physico-chemical barrier and/or the release of various chemical messengers by the EE.

Animals↗