摘要:

Endothelium plays a key role in modulating vascular tone through the production of vasodilator and vasoconstrictor substances. In animals, experimental hypertension is associated with endothelial dysfunction. In human hypertension, available evidence indicates the presence of a reduced basal production of nitric oxide and of an impaired vasodilation to the endothelium-dependent agonist acetylcholine or to the chemically related methacholine in the forearm and coronary vasculature. This abnormal response to endothelium-dependent agonists seems to be caused by the simultaneous presence of an alteration in the L-arginine-nitric oxide pathway and the production of cyclooxygenase-derived constrictor prostanoids. The reduced basal production of nitric oxide seems to be secondary to blood pressure increase while, at variance with observations in animals, it is possible that the impaired agonist-evoked endothelium-dependent vasodilation could be a primary phenomenon since it can be detected in young normotensive subjects with essential hypertensive parents. In addition aging can contribute to the endothelial dysfunction associated with essential hypertension. Finally, in essential hypertensive patients, non-pharmacological treatment through potassium administration seems to enhance endothelium-dependent vasodilation whereas, albeit scanty data are available, chronic effective pharmacological treatment, while restoring a normal basal production of nitric oxide, does not restore or at least improve the vascular response to endothelial agonists. Thus endothelial dysfunction is associated with essential hypertension and could play an important role in the pathophysiology and cardiovascular complications of the disease.

ISSN:1062-3329    

DOI:10.3109/10623329609024676

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Gram-negative (Salmonella typhimuriumporins and lipopolysaccharide-R), and Gram-positive bacterial components (lipoteichoic acid, muramic acid, muramyl-dipeptide, adjuvant peptide, protein A, toxic shock syndrome toxin-1,α-hemolysin) were tested for their ability to stimulate both the release of Granulocyte-Monocyte Colony Stimulating Factor (GM-CSF), soluble Intercellular Adhesion Molecule-1 (ICAM-1) and soluble E-selectin from human endothelial cells, and the surface expression of the adhesion molecules.Salmonella typhimuriumporins and lipopolysaccharide-R (LPS-R) were able to induce the release of GM-CSF, sE-selectin and sICAM-1 in a dose dependent fashion. The greatest release of these factors was obtained using pork at a concentration of 5μg/ml and LPS-R at a concentration of 1μg/ml. The kinetics of release showed that LPS-R was able to stimulate the production of these factors earlier than porins but at a lower rate. Porins and LPS-R was also able to up-regulate the surface expression of E-selectin and ICAM-1 on endothelial cells. Among the other bacterial components, onlyα-hemolysin was found to actively induce the release of sE-selectin in a dose dependent fashion; the maximal release of sE-selectin was obtained usingα-hemolysin at a concentration of 100 ng/ml. This toxin also increased the E-selectin expression, on the cell surface. Lipoteichoic acid, muramic acid, muramyl-dipeptide, adjuvant peptide, protein A, toxic shock syndrome toxin-1 showed no activity in our experimental conditions.

ISSN:1062-3329    

DOI:10.3109/10623329609024677

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

We investigated the actions of the two structurally similar but genetically distinct endothelium-derived vasoactive natriuretic peptides, C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP), upon isolated human internal mammary arteries and saphenous veins. Based upon previous studies in canine arteries and veins, we hypothesized that CNP would selectively cause relaxation of human veins while ANP would be selective for human arteries. Rings with and without endothelium of human internal mammary arteries and saphenous veins from patients under going coronary artery bypass grafting were suspended for measurement of isometric force in an organ chamber. CNP caused significant concentration-dependent relaxations in saphenous veins with and without endothelium contracted with phenylephrine (10−6M). In marked contrast, ANP caused no relaxation in saphenous veins either with or without endothelium. In rings of internal mammary arteries, ANP caused significant concentration-dependent relaxations in internal mammary arteries with and without endothelium contracted with phenylephrine (10−6M), while CNP induced relaxations which were less than those observed to ANP. These results demonstrate that CNP relaxes both human saphenous veins and internal mammary arteries. In contrast, ANP is a relaxing factor of isolated human internal mammary arteries but not of human saphenous veins. These studies are consistent with distinct biological roles for CNP and ANP in human vessels.

ISSN:1062-3329    

DOI:10.3109/10623329609024678

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

In coronary endothelium, bradykinin (BK) modulates production of vasodilators by stimulating Ca2+influx. To examine the ionic currents involved in this process, we applied BK (100 nM) to single bovine coronary venular endothelial cells (CVEC) while recording membrane potential (Em) or whole-cell current simultaneously with [Ca2+]i. The resting potential (Er) of unstimulated cells was bimodally distributed (-70±9 mV,n= 26; -15±8 mV,n= 30). Irrespective of Er, BK evoked a biphasic [Ca2+]iincrease simultaneously with a change in Em. When Erwas negative to -30 mV, depolarizations were typically observed. When Erwas positive to -30 mV, transient hyperpolarizations were typically observed. Under voltage clamp, [Ca2+], increased as the membrane hyperpolarized and the ratioΔ[Ca2+]i/ΔEmwas greater in the presence of BK than in unstimulated cells. Many, but not all, cells exhibited an outward K+current that appeared to be Ca2+dependent. When present, this current typically predominated over other currents and resulted in hyperpolarizations. When K+currents were small or blocked, two inward currents were recorded. The first was a large (-224±20 pA at -70 mV), rapidly activating current carried by Cl-. The second was a smaller (-81±9 pA at -70 mV) cationic current carried in part by Ca2+. These data suggest that BK activates at least three distinct currents in CVECs: a K+-current, a Cl−-current, and a nonselective cation current. The predominance of one or more of these currents in an individual cell presumably determines that cell's electrophysiological response to BK.

ISSN:1062-3329    

DOI:10.3109/10623329609024679

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Endothelin (ET)-1 and ET-3 elicited relaxations at 1 nM and contractions at 10 nM or higher, whereas IRL1620 induced only relaxation in dog pulmonary arteries. The relaxations by ET-1, ET-3 and IRL1620 were not affected by indomethacin, but were abolished by endothelium denudation or NG-nitro-L-arginine. The relaxations caused by ET-3 and IRL1620 were markedly suppressed by IRL1038. BQ123 potentiated ET-1-, ET-3- and IRL1620-induced relaxations and markedly suppressed ET-1- and ET-3-induced contractions. ET-1, ET-3 and IRL1620 produced only contraction in pulmonary venous strips; the order of potency was ET-1>ET-3>IRL1620. The contraction induced by ET-1 was markedly suppressed by BQ123. This ETAantagonist also suppressed the ET-3-induced contraction. Under ETAreceptor blockade, EŤ-3 (30 nM) produced endothelium-independent relaxation, which was abolished by indomethacin. IRL1038 suppressed the IRL1620-induced contraction. It is concluded that pulmonary arterial and venous responses to ET can be attributed mainly to activation of ETAand ETBreceptors; ETAreceptors located in the smooth muscle mediate contractions in the arteries and veins. It appears that ETBreceptors located in the arterial endothelium mediate relaxations via release of EDRF/NO, whereas those located in venous smooth muscle mediate contractions. Non ETA/non ETBreceptors in the venous smooth muscle are likely to participate in prostaglandin-mediated relaxation.

ISSN:1062-3329    

DOI:10.3109/10623329609024680

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Vascular endothelial cells release bradykinin (BK), which acts in an autocrine manner to raise intracellular calcium concentrations ([Ca2+]i) and release NO, effects which can be modified by angiotensin-converting enzyme (ACE) inhibitors. Little is known of the effects of BK and ACE inhibitors on endocardial endothelium however. In this study, we investigated the effects of the ACE inhibitors captopril and ramiprilat on (a) BK-degrading activity, (b) resting Ca2+homeostasis and (c) BK-induced changes in [Ca2+]i and cGMP in bovine aortic endothelial (BAE) and right ventricle endocardial (BRVE) cells. Captopril and ramiprilat inhibited the BK-degrading activity of both cell types. Resting levels of [Ca2+]i and cGMP were significantly higher in BRVE than in BAE. Captopril or ramiprilat did not alter resting [Ca*+]i, but caused significant increases in resting cGMP which were reduced by the NO synthase inhibitor L-nitroarginine benzyl ester and the B2-kinin receptor antagonist HOE 140. Captopril and ramiprilat enhanced the peak Ca2+reponses to exogenous BK in both cell types, while having no effect on BK-induced increases in cGMP. These data demonstrate that endocardial endothelial cells, like vascular endothelial cells, possess ACE activity which may modulate the activity of endogenous kinins.

ISSN:1062-3329    

DOI:10.3109/10623329609024681

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

A porphyrinic sensor was developed and used to monitor the release of nitric oxide (NO) by a fetal bovine aorta endothelial (FBAE) cell culture and a primary bovine aorta endothelial (BAE) cell culture, with populations of several thousand cells. The sensor consisted of either a platinum mesh or reticulated vitreous carbon support covered with several layers of a p-type semiconducting metalloporphyrin and a cation exchanger, Nafion. Tissue and cell cultures can be grown directly on the surface of the sensor and NO release can be measured by amperometric or differential pulse voltammetry methods. The detection limit of the sensor deposited on reticulated vitrous carbon and platinum mesh support is 10 nM and 0.1μM respectively. The response time is about one millisecond and precision 5-6%. The peak NO concentration released from FBAE cells was 190±20 nM and 70±20 nM when agonized by calcium ionophore (A23187) and bradykinin respectively. The maximum NO concentration released from the primary culture BAE cells was 770±50 nM and 400±50 nM when agonized by angiotensin II and bradykinin respectively.

ISSN:1062-3329    

DOI:10.3109/10623329609024682

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

There is evidence that long-term changes in the innervation of vascular smooth muscle alters the flow-stimulated release of vasoactive substances from the endothelium. To investigate the endothelial content of these substances following chronic sensory denervation, the distribution of endotheli-1 (ET-l), substance P (SP) and arginine vasopressin (AVP) in mature rat pulmonary artery endothelial cells was examined after neonatal treatment with the selective sensory neurotoxin, capsaicin. After immunolabelling with antibodies to the vasoactive peptides, Häutchen preparations of sheets of endothelial cells were observed and the percentage of immunopositive cells recorded. Preparations from capsaicin-treated rats displayed significantly more cells immunopositive to SP than controls (36%±3, n = 4 versus 9%±4, n = 4, P<0.01) and less cells immunopositive to ET-1 (36%±4, n = 4 versus 56%±3, n = 4, P<0.01). The distribution of vasopressin-immunopositive cells was unchanged by capsaicin treatment (10%±4, n = 4). Increased expression of SP and decreased expression of ET-1 in endothelial cells as a consequence of long-term sensory denervation may be a compensatory mechanism within the vessel to maintain an appropriate vascular tone.

ISSN:1062-3329    

DOI:10.3109/10623329609024683

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor