Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ENDOTHELIUM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed2001

Role of endothelium in the action of isoflurane on vascular smooth muscle of isolated mesenteric resistance arteries.

BACKGROUND: It is believed that isoflurane decreases blood pressure predominantly by decreasing systemic vascular resistance with modest myocardial depression. Nevertheless, little information is available regarding the direct action of isoflurane on systemic resistance arteries. METHODS: With use of the isometric force recording method, the action of isoflurane on contractile response to norepinephrine, a neurotransmitter that plays a central role in sympathetic maintenance of vascular tone in vivo, was investigated in isolated rat small mesenteric arteries. RESULTS: In the endothelium-intact strips, the norepinephrine response was initially enhanced after application of isoflurane (2-5%), but it was subsequently almost normalized to the control level during exposure to isoflurane. However, the norepinephrine response was notably inhibited after washout of isoflurane. In the endothelium-denuded strips, the norepinephrine response was gradually inhibited during exposure to isoflurane (> or = 3%), and the inhibition was prolonged after wash-out of isoflurane. The isoflurane-induced enhancement of norepinephrine response was still observed after inhibitions of the nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase and lipoxygenase pathways, or after blockade of endothelin-1, angiotensin-II, and serotonin receptors; however, it was prevented by superoxide dismutase. CONCLUSIONS: In isolated mesenteric resistance artery, the action of isoflurane on contractile response to norepinephrine consists of two distinct components: an endothelium-dependent enhancing component and an endothelium-independent inhibitory component. During exposure to isoflurane, the former counteracted the latter, preventing the norepinephrine response from being strongly inhibited. However, only the endothelium-independent component persists after washout of isoflurane, causing prolonged inhibition of the norepinephrine response. Superoxide anions may be involved in the enhanced response to norepinephrine.

Acetylcholine↗
PubMed1988

Ageing suppresses endothelium-dependent relaxation and generates contraction mediated by the muscarinic receptors in vascular smooth muscle of normotensive Wistar-Kyoto and spontaneously hypertensive rats.

We evaluated the effects of ageing and hypertension on endothelium-dependent relaxation and contraction of vascular smooth muscles. Aortic rings with and without endothelium from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), divided into young, adult and old groups, were examined for relaxation in response to acetylcholine, adenosine triphosphate (ATP) and sodium nitroprusside. Relaxation responses to acetylcholine and ATP in SHR were either equal to or greater than those in WKY. Relaxations induced by ATP were not altered by ageing, while the degree of acetylcholine-induced endothelium-dependent relaxations was in an inverse order of age in both SHR and WKY. In old SHR and WKY and adult SHR, lower doses of acetylcholine caused relaxations, but increases in the dose of acetylcholine induced contraction. Acetylcholine-induced contractions were abolished by indomethacin or endothelium rubbing. We conclude that endothelium-dependent relaxations are not diminished by spontaneous hypertension but the relaxations mediated by the muscarinic receptors are reduced with ageing. Further, acetylcholine causes endothelium-dependent contractions by releasing cyclo-oxygenase products, not only in SHR but also in aged normotensive WKY.

Acetylcholine↗
PubMed1993

Phospholipid vesicles (liposomes) restore endothelium-dependent cholinergic relaxation in thoracic aorta from spontaneously hypertensive rats.

OBJECTIVE: The present study was designed to examine, using isolated preparations of thoracic aorta, the effects of artificial phosphatidylcholine vesicles (liposomes) on vascular endothelium-dependent responses in spontaneously hypertensive rats (SHR) compared with those in Wistar-Kyoto (WKY) normotensive rats. DESIGN: Phosphatidylcholine liposomes, which possess the ability to repair the plasma membrane of living cells, were used in these experiments. METHODS: Liposomes were prepared from egg phosphatidylcholine. A suspension of lipid was subjected to ultrasound treatment at 20 degrees C at a frequency of 44 kHz for 45 s. The contraction of vascular smooth muscle was recorded using a force-displacement transducer coupled with a physiograph. RESULTS: It was shown that aortic smooth muscle from SHR demonstrated a loss of endothelium-dependent relaxation in acetylcholine (10(-6) mol/l) compared with WKY rat aortic smooth muscle. Liposomes in a concentration of 100-125 micrograms/ml restored these endothelium-dependent responses more effectively than L-arginine (10(-5) to 10(-4) mol/l), which is known to be a precursor of endothelium-derived relaxing factor (EDRF). This effect was not observed in denuded aortic rings, and liposomes lost their ability of repairing endothelium-dependent vascular relaxant responses in the presence of methylene blue (5 x 10(-5) mol/l), which inhibits soluble guanylyl cyclase activation by nitric oxide (NO), and N omega-nitro-L-arginine (L-NNA, 5 x 10(-5) to 10(-4) mol/l), a potent and selective inhibitor of NO synthase. CONCLUSION: The present results suggest that the loss of vascular endothelium-dependent responses in SHR may be, at least partly, due to endothelial cells membrane damage, and that the phosphatidylcholine liposomes can repair the function of endothelial cells and restore synthesis or release, or both, of EDRF in hypertension.

Acetylcholine↗
PubMed1991

Nebivolol induces endothelium-dependent relaxations of canine coronary arteries.

Nebivolol is a new beta 1-antagonist that acutely reduces arterial blood pressure without depressing cardiac function. The present study was designed to determine the effect of nebivolol on coronary arteries. Rings of canine left anterior descending coronary (LAD) artery with or without endothelium were suspended in organ chambers and the isometric tension was recorded. In some experiments, the transmembrane potential of the smooth muscle cells was recorded by electrophysiological methods. During contractions to prostaglandin F2 alpha, nebivolol induced concentration-dependent relaxations of the coronary arteries. The enantiomer, l-nebivolol, also induced comparable relaxations; however, d-nebivolol induced smaller relaxations. The relaxations induced by nebivolol and its enantiomer were significantly larger in tissues with than in those without endothelium. The differences between tissues with and without endothelium were abolished by nitro-L-arginine (3 x 10(-5) M) or methylene blue (10(-5) M). The nebivolol-induced relaxations were not affected by indomethacin (10(-5) M), phentolamine (5 x 10(-6) M), propranolol (5 x 10(-6) M), or methysergide (3 x 10(-6) M). Nebivolol at a subthreshold concentration for inducing relaxation (3 x 10(-7) M) did not significantly affect endothelium-dependent relaxations to acetylcholine but potentiated ADP-induced endothelium-dependent relaxations. The potentiation is stereoselective for l-nebivolol. Nebivolol induced a small hyperpolarization of the coronary smooth muscle with endothelium (1 mV).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1992

Effects of chronic treatment with SQ29852 on spontaneous smooth muscle tone and endothelium-dependent relaxation in aorta of stroke-prone spontaneously hypertensive rats.

The effects of chronic treatment with SQ29852, an angiotensin-converting enzyme inhibitor, on spontaneous smooth muscle tone and endothelium-dependent relaxation of aorta from stroke-prone spontaneously hypertensive rats (SHRSP) were studied and compared with those of captopril. Endothelium-removed aorta from 16-week-old SHRSP exhibited a high amplitude of spontaneously developed active tension (active tone), whereas no active tone was observed in the preparation from control normotensive Wistar-Kyoto (WKY) rats. Treatment with SQ29852 or captopril at age 5-16 weeks prevented the development of hypertension. No active tone could be detected in the preparation from SQ29852-treated SHRSP. Endothelium-dependent relaxation was markedly reduced in the preparation from nontreated SHRSP compared with WKY rats. Treatment with SQ29852 prevented the impairment of endothelium-dependent relaxation. It was also shown that norepinephrine-induced contraction was markedly depressed in endothelium-intact aorta from SQ29852-treated rats. The effects of SQ29852 were more prominent than those of hydralazine when blood pressure was maintained at similar levels. It was suggested that SQ29852 exerts an action on both vascular smooth muscle and endothelium that is mediated by the inhibition of angiotension-converting enzyme in addition to indirect actions of SQ29852 that are brought about by blood pressure lowering.

Acetylcholine↗
PubMed1992

Endothelium-dependent contraction produced by acetylcholine and relaxation produced by histamine in monkey basilar arteries.

The present experiments were carried out to investigate the endothelium dependence of the responses to acetylcholine (ACh), arachidonic acid, and histamine in monkey basilar arteries. ACh and arachidonic acid caused endothelium-dependent contraction (EC) in both monkey and canine basilar arteries. The endothelium-derived contracting factor (EDCF) was probably thromboxane A2 (TxA2), as the EDC was attenuated by a cyclooxygenase inhibitor, TxA2 synthetase inhibitors, and TxA2 antagonists. On the other hand, histamine caused endothelium-dependent relaxation (EDR) in monkey and EDC in canine basilar arteries. The EDR in monkey basilar arteries was attenuated by a nitric oxide synthase inhibitor. The EDR and EDC were antagonized by tripelennamine but not by cimetidine, indicating that they are mediated by H1-receptors. From these results, we suggest that in the monkey basilar artery, either there are two types of endothelium (an EDCF type for ACh and arachidonic acid and an EDRF type for histamine) or there is a single type of endothelium with two types of signalling processes (one for EDC and one for EDR).

Acetylcholine↗
PubMed1993

Endothelium, mechanical compliance, and cGMP content in the carotid artery from spontaneously hypertensive rats.

An experimental model of in situ isolated carotid arteries has been used to evaluate the static mechanical properties of the arterial wall in 12-week-old Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). The effects of endothelium removal on the carotid compliance (CC) were compared to the effects of total abolition of the vascular smooth muscle tone by potassium cyanide (KCN). CC measured for pressures ranging from 50 to 175 mm Hg had maximal values (0.22 +/- 0.07 and 0.13 +/- 0.03 microliters/mm Hg, respectively, for WKY rats and SHRs, p < 0.001) for pressure close to the mean arterial pressure (operating pressures). Operating values of CC were increased by 35 and by 45% in WKY rats and SHRs, respectively, after KCN poisoning (p < 0.01). The endothelium removal induced a significant increase in CC compared to their control values (+37%, p < 0.01 and +25%, p < 0.01, respectively, in WKY rats and SHRs). With intact endothelium, carotid cGMP level was higher in SHRs than in WKY rats (30.3 +/- 3.7 vs. 19.7 +/- 2.3 fmol/mg tissue, p < 0.02). After endothelium removal, tissue cGMP was reduced by 28% in WKY rats (p < 0.02) and by 90% in SHRs (p < 0.001). The present results suggest that the mechanical properties of the wall of the carotid artery are endothelium-dependent. CC for operating pressure was significantly increased after endothelium removal in both strains. Furthermore, the cGMP pathway seems to be more activated in the carotid wall from SHRs than from WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Role of endothelium in hyperpolarization of coronary smooth muscle by adenosine and its analogues.

We studied the effects of adenosine (AD) and its analogues, 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD) on membrane potential of porcine coronary artery with an without endothelium, conducting experiments with addition of indomethacin (10(-5) M) to rule out involvement of prostanoids. Average resting membrane potential (RMP) in porcine coronary artery was -51.1 +/- 0.2 and -50.3 +/- 0.2 mV, with and without endothelium, respectively. AD agonists at 10(-5) M caused a significant increase in RMP to -69.5 +/- 0.2 mV for AD, to -82.2 +/- 0.3 mV for CAD, and to -81.2 +/- 0.3 mV for NECA in porcine coronary arteries with intact endothelium. Moreover, AD agonists at 10(-5) M caused a smaller but significant increase in RMP to -54.3 +/- 0.2 mV for AD, -56.1 +/- 0.1 mV for CAD, and -61.1 +/- 0.2 mV for NECA without endothelium. The average RMP for human coronary artery with and without endothelium was -66.1 +/- 0.5 and -64.0 +/- 0.4, respectively. Qualitatively, similar effects of AD and its analogues were observed in two human coronary arteries. The AD receptor antagonist, 8-sulfophenyltheophylline (8-SPT, 10(-5) M) blocked hyperpolarization caused by AD and its analogues with and without endothelium both in porcine and human coronary arteries. The hyperpolarization caused by CAD and NECA in porcine coronary artery was attenuated in part by the nitric oxide (NO) synthase inhibitors N-monomethyl-L-arginine (L-NMMA, 10(-5) M) and N-nitro-L-arginine methylester (L-NAME, 10(-5) M), and the effect of L-NAME was reversed by L-arginine (L-ARG, 10(-4) M).(ABSTRACT TRUNCATED AT 250 WORDS)

2-Chloroadenosine↗
PubMed1996

The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation.

Endothelium-dependent relaxations are achieved by a combination of endothelium-derived prostacyclin (PGI2), nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). However, it remains to be fully clarified whether the relative contribution of these three mechanisms to endothelium-dependent relaxations varies as a function of the vessel size. This study was designed to clarify this point. Acetylcholine (ACh)-induced endothelium-dependent relaxations were examined in isolated blood vessels taken from the aorta and the proximal and distal mesenteric arteries of the rat. The contributions of PGI2, NO, and EDHF were evaluated by the inhibitory effects of indomethacin, N omega-nitro-L-arginine methyl ester (L-NAME) in the presence of indomethacin, and KCl in the presence of indomethacin and L-NAME, respectively. The membrane potentials were recorded with microelectrodes. The expression of endothelial No synthase (eNOS) was examined by both immunostaining and immunoblotting. The contribution of PGI2 was negligible in three different-sized blood vessels. The contribution of NO was most prominent in the aorta, whereas that of EDHF was most prominent in the distal mesenteric arteries. The resting membrane potential was significantly deeper and the ACh-induced hyperpolarization was greater in the distal mesenteric arteries than those in the aorta. The expression of eNOS was the highest in the aorta and the lowest in the distal mesenteric arteries. These results indicate that the importance of EDHF increases as the vessel size decreases in endothelium-dependent relaxations in the rat mesenteric circulation.

Acetylcholine↗
PubMed1997

Short-term estrogen augments both nitric oxide-mediated and non-nitric oxide-mediated endothelium-dependent forearm vasodilation in postmenopausal women.

Estrogen is known to improve in the short term the impaired endothelium-dependent vasodilating responses in postmenopausal women, which may account in part for the beneficial cardiovascular effects of the female hormone. Endothelium-dependent vasodilation is achieved by combined effects of endothelium-derived prostacyclin, nitric oxide (NO), and hyperpolarizing factor. In this study, we investigated our hypothesis that short-term estrogen improves both NO-mediated and non-NO-mediated endothelium-dependent vasodilation in postmenopausal women. The study included 12 postmenopausal women (aged 64 +/- 3 years). The forearm blood flow was measured by strain-gauge plethysmography. The forearm vascular responses to the endothelium-dependent vasodilators, acetylcholine and substance P, were examined before and after intravenous administration of conjugated estrogen and subsequently after intraarterial infusion of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis. Short-term estrogen augmented the forearm vasodilating responses to both acetylcholine and substance P. The treatment with L-NMMA almost abolished the augmented response to acetylcholine but did not affect that to substance P. The forearm vascular response to sodium nitroprusside was unchanged by the estrogen administration. These results indicate that estrogen augments (in the short-term) both NO-mediated and non-NO-mediated endothelium-dependent forearm vasodilation in postmenopausal women. Thus the beneficial effect of estrogen on endothelial vasodilator function appears to extend to non-NO-dependent mechanism(s).

Aged↗
PubMed2004

Cross talk between angiotensin II and alpha 1 adrenergic receptors in rabbit aorta: role of endothelium.

Interaction between the renin-angiotensin system and the sympathetic nervous system has been proposed to be like a physiological regulation mechanism. The present work was designed to study the cross talk between angiotensin II and adrenergic receptors on the smooth muscle contractile response and the endothelium influence in this phenomenon. Homologous and endothelium independent desensitization of angiotensin II-contractile response was observed. Treatment with noradrenaline between two cumulative doses response curves (CDRC) to angiotensin II caused a rightward shift of the second CDRC in unrubbed arteries and increased the maximal response in rubbed arteries. Prazosin blocked these effects. No homologous desensitization of noradrenaline contractile response was found. Treatment with angiotensin II between two CDRC to noradrenaline caused a loss of affinity in the second CDRC in unrubbed arteries. Losartan was able to avoid this phenomenon. Maximal response was enhanced both in arteries with and without endothelium treated or not with angiotensin II. Results demonstrate homologous and endothelium-independent desensitization of the contractile response to angiotensin II but not to noradrenaline. In addition, heterologous and endothelium-dependent desensitization induced by noradrenaline and angiotensin II on the contractile response to each other was found. Furthermore, results provided the first evidence that there is an endothelium-dependent cross talk between alpha1-adrenergic and angiotensin II receptors in smooth muscle of rabbit aorta.

Animals↗
PubMed1982

Expression of RT1.A and RT1.B/D antigens on endothelium of rat kidneys.

The presence of major histocompatibility complex (MHC)-encoded antigens (RT1) on endothelium of rat kidneys was investigated using hyperimmune allogeneic rat sera (HIS) in an indirect immunofluorescence technique with kidney sections. Endothelial antigens detected with anti-MHC sera segregated in an F2 generation with the RT1 antigens on erythrocytes. The MHC specificity of the endothelial staining was established with kidneys from congenic strains. The existence of public and private determinants on endothelium was shown by absorption experiments with spleen cells from several strains. RT1.A antigens were demonstrated on the endothelium of arteries, capillaries, and veins, using purified anti-RT1.A antibodies. This was confirmed using the MHC-recombinant PVG.1R strain. RT1.B/D antigens were found on the endothelium of capillaries and veins of the same strain. Furthermore, red blood cell-absorbed HIS, monoclonal anti-Ia antibodies, and mouse alloantisera which cross-react with rat Ia-like antigens were used. Based on this cross-reactivity, it appeared that I-E/C-like but not I-A-like antigens were detected on endothelium. RT1.C region antigens were not detected. Antisera against RT2, Ag-F, Ag-S, and immunoglobulin allotypes did not bind to normal kidneys. We conclude that RT1.A and some RT1.B/D specificities are expressed on rat renal endothelium.

Animals↗
PubMed2005

Sepsis up-regulates the expression of connexin 40 in rat aortic endothelium.

OBJECTIVE: A distinctive feature of sepsis is a pleiotropic modification of membrane protein expression in the vascular endothelium, associated with diminished endothelium-dependent relaxation (endothelial dysfunction). In cultured endothelial cells, inflammatory stimuli alter expression of connexins (Cx), proteins that make up the gap junctions responsible for intercellular communication. In the present study, we tested whether the polymicrobial sepsis induced by cecal ligation and perforation in the rat alters the expression of the connexins present in the vascular endothelium (i.e., Cx37, Cx40, and Cx43). We also examined a possible association between such changes and endothelial dysfunction in this model. DESIGN: Animal study, with two parallel groups. SETTING: Animal research facility. SUBJECTS: One hundred four male adult Wistar rats. INTERVENTIONS: Rats underwent either cecal ligation and perforation to induce sepsis or a sham operation and were killed after a variable time, mostly 24 hrs. MEASUREMENTS AND MAIN RESULTS: Experiments designed to test for the impact of sepsis on connexin expression disclosed a three-fold increase in Cx40 messenger RNA and protein in the aorta, an effect that peaked at 24 hrs after cecal ligation and perforation, was specific to this connexin (i.e., levels of Cx37 and Cx43 did not vary), and was restricted to the aortic endothelium. Experiments designed to test the permeability of interendothelial gap junctions using the scrape-loading method did not show a change in function in the septic group. Finally, a time-course study was designed to test for a possible association of enhanced Cx40 expression with endothelial dysfunction. Endothelium-dependent relaxation was diminished in rings of aorta when harvested from septic rats before (6 hrs after surgery) but not at the time when enhanced Cx40 expression occurred (12 and 24 hrs). CONCLUSION: In this experimental model, recovery from an early transient dysfunction of the aortic endothelium is associated with an enhanced expression of aortic endothelial Cx40.

Animals↗
PubMed2005

Captopril restores endothelium-dependent relaxation induced by advanced oxidation protein products in rat aorta.

To explore whether advanced oxidation protein products (AOPP) can cause endothelial dysfunction in vitro, and whether captopril exerts beneficial effect on impaired endothelium-dependent relaxation induced by exogenous advanced oxidation protein products and to investigate the potential mechanisms. Both the Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside-induced endothelium-independent relaxation of aortic rings were measured by recording isometric tension after the rings were exposed to AOPP-BSA in the absence or presence of captopril to assess the injury effect of AOPP-BSA and the protective effect of captopril on the aortic endothelium, respectively. Co-incubation of aortic rings with AOPP-BSA (3 mmol/L) for 90 minutes resulted in a significant inhibition of EDR to ACh, but had no effects on endothelium-independent relaxation to SNP. After incubation of the rings in the co-presence of captopril (3 to 30 micromol/L) or enalaprilat (30 micromol/L) with AOPP-BSA (3 mmol/L) for 90 minutes, captopril significantly and enalaprilat only partly attenuated the inhibition of EDR induced by AOPP-BSA. This protective effect of captopril (30 micromol/L) was abolished by N-nitro-L-arginine methyl ester (10 micromol/L), an inhibitor of nitric oxide synthase. Furthermore, the superoxide anion scavenger superoxide dismutase (SOD, 200 U/mL), and the nitric oxide precursor L-arginine (3 mmol/L) also ameliorated the impaired EDR caused by AOPP-BSA. But D-arginine had no effect on the impaired EDR caused by AOPP-BSA. AOPP-BSA can trigger endothelial dysfunction and captopril can protect the endothelium against functional damage induced by AOPP-BSA in rat aorta, increase nitric oxide bioavailability. The mechanisms of endothelial dysfunction induced by AOPP-BSA may include the decrease of NO and the generation of oxygen-free radicals.

Animals↗
PubMed2006

Enhanced endothelium-dependent vasodilatation by dual endothelin receptor blockade in individuals with insulin resistance.

Insulin resistance is associated with endothelial dysfunction and increased production of the pro-inflammatory vasoconstrictor peptide endothelin-1 (ET-1). The aim of this study was to test the hypothesis that blockade of ET receptors results in enhanced endothelium-dependent vasodilatation (EDV) in individuals with insulin resistance. Twelve individuals with insulin resistance without any history of diabetes or cardiovascular disease and 8 age-matched controls with high insulin sensitivity, as determined by hyperinsulinemic-euglycemic clamp, were investigated on 2 separate occasions using forearm venous occlusion plethysmography. Endothelium-dependent and endothelium-independent vasodilatation was determined before and after selective ET(A) and dual ET(A)/ET(B) receptor blockade. A 60 minute intraarterial infusion of the ET(A) receptor antagonist BQ123 (10 nmol/min) combined with the ET(B) receptor antagonist BQ788 (5 nmol/min) evoked a significant increase in acetylcholine-mediated EDV (P < 0.01) in individuals with insulin resistance. The endothelium-independent vasodilator response to nitroprusside was not changed by dual ET(A)/ET(B) receptor blockade. Dual ET(A)/ET(B) receptor blockade did not affect the response to acetylcholine or nitroprusside in the insulin-sensitive group. Selective ET(A) receptor blockade did not evoke any changes in endothelium-dependent or endothelium-independent vasodilatation in either group. This study demonstrates that dual ET(A)/ET(B) receptor blockade, but not selective ET(A) blockade, enhances EDV in subjects with insulin resistance, suggesting that ET-1 is involved in the regulation of endothelial function in individuals with insulin resistance.

Endothelin A Receptor Antagonists↗
PubMed2006

Role of membrane potential in endothelium-dependent relaxation of isolated mouse main pulmonary artery.

The physiology of smooth muscle and endothelial cells of a particular vascular bed and from different species differs from each other. Acetylcholine causes an endothelium-dependent relaxation of preconstricted pulmonary arteries from the rat. This relaxation is mediated by nitric oxide (NO) plus a yet-unidentified endothelium-derived hyperpolarizing factor, which relaxes the smooth muscles by hyperpolarizing them. Our aim is to test whether these observations could be generalized to the smooth muscle cells from the mouse pulmonary artery. Smooth muscle or endothelial cell membrane potential of strips of murine pulmonary artery were measured simultaneously with the force developed by the strip. Acetylcholine hyperpolarized the endothelial cells. However, acetylcholine did not induce an endothelium-dependent hyperpolarization of the smooth muscle, while it relaxed the strip in an endothelium-dependent manner. This relaxation was abolished by an inhibitor of NO synthesis, nitro-L-arginine. Moreover, nitroglycerin relaxed the strips without changing the membrane potential of the smooth muscle cells. Injection of Lucifer yellow into the endothelial cells and the smooth muscle cells did not show heterocellular dye coupling. Furthermore, electron microscopy did not show gap junction plate at the myoendothelial junctions. We conclude that in the mouse main pulmonary artery, NO alone is responsible for the acetylcholine-induced endothelium-dependent vasodilatation, whereas the phenomenon called endothelium-derived hyperpolizing factor is not present. Therefore, caution should be taken when comparing different animal models to study pulmonary circulation and its reactivity.

Animals↗
PubMed1997

Cloning of the mouse laminin alpha 4 cDNA. Expression in a subset of endothelium.

Endothelial cells express a 400-kDa or 240-kDa laminin alpha chain, depending on their tissue of origin or physiological state [1, 2]. Using differential display and subsequent screening of a mouse endothelial cell cDNA library we here identify the gene coding for the 240-kDa laminin chain as the laminin alpha 4 gene. The complete mouse laminin alpha 4 cDNA sequence is reported and compared with other laminin alpha chains. In situ hybridization of embryonic and new born mouse tissues revealed expression of laminin alpha 4 mRNA in a subset of endothelium, in particular aortic endothelium, endocardium and endothelium of blood vessels in the skin and in the brain. Strong laminin alpha 4 expression by aortic endothelia was confirmed by data obtained from cultured bovine aortic endothelial cells (BAEC). Isolation of laminin from BAEC conditioned medium revealed a Y-shaped molecule in rotary shadowing. Subsequent sequencing of BAEC laminin resulted in laminin alpha 4, beta 1 and gamma 1 amino acid sequences, confirming that laminin alpha 4 is one of the major laminin alpha chains expressed by aortic endothelium not only in the mouse. In addition, strong laminin alpha 4 mRNA expression occurred in peripheral nerves, cardiac muscle, fat, the dermis of the skin and lung stroma of mouse tissues. The data demonstrate a cytokine and progesterone-regulated differential expression of laminin alpha 4 mRNA in mouse endothelium, suggesting a distinct functional role for this laminin chain in endothelium.

Amino Acid Sequence↗
PubMedDate not supplied

Role of endothelium-derived hyperpolarizing factor in endothelial dysfunction during diabetes.

1. Under normal conditions, the endothelium plays a major role in the maintenance of vasodilatory tone via the production of endothelium-derived vasodilator agents, such as prostacyclin, nitric oxide and endothelium-derived hyperpolarizing factor (EDHF). Inhibition of endothelium-dependent relaxation features prominently in a range of cardiovascular diseases, including hypertension, coronary artery disease and diabetes. 2. Endothelium-derived hyperpolarizing factor is a prominent vasodilator, particularly in smaller arteries and arterioles. There is now emerging evidence to suggest that EDHF may play a role in the endothelial dysfunction in diabetes. 3. Since the first description of endothelium-dependent hyperpolarization some 20 years ago, it has emerged that EDHF is heterogeneous in nature, consisting of diffusible factors and contact-mediated mechanisms. The specific identity of EDHF in any particular vascular bed may influence the impact of diabetes on vascular function. 4. There is accumulating evidence in diabetic rat models and humans showing impaired EDHF activity in small resistance vessels. In contrast, studies in mice suggest that EDHF activity is actually enhanced under diabetic conditions. 5. It is clear that alterations in EDHF activity may have an important contribution in diabetes, more specifically in contributing to microvascular complications observed under diabetic conditions.

Animals↗