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Biomedical subjects

M Boros

Publications and source records attributed to M Boros.

At least 37 records · Page 2Linked to original sources
PubMed1999

Endothelin-A receptor antagonism improves small bowel graft perfusion and structure after ischemia and reperfusion.

BACKGROUND: We hypothesized that endothelin-A (ET-A) receptor activation plays a central role in intestinal ischemia-reperfusion-induced hemodynamic changes and may trigger the process of mucosal barrier destruction. Our aims were to investigate and compare the effects of systemic and intragraft ET-A receptor antagonist therapy during the early revascularization phase of small bowel transplants. METHODS: In Groups 1, 2, and 3 orthotopic small bowel autotransplants were performed in anesthetized dogs. Group 4 served as sham-operated control. Group 2 was treated i.v. with the ET-A receptor antagonist ETR-p1/fl peptide at the onset of reperfusion. In Group 3, intragraft infusion of the ETR-p1/fl peptide was applied during cold ischemia. The mucosal myeloperoxidase activity and the free radical-producing capacity of the granulocytes passing the intestinal graft were determined, and the systemic hemodynamic features were recorded. The extent of the mucosal injury was determined from tissue biopsies taken after 4 hr of reperfusion. RESULTS: Reperfusion progressively decreased the mesenteric blood flow, increased the mesenteric vascular resistance, and enhanced the accumulation and free radical production capacity of the leukocytes. These changes were significantly inhibited in Group 2 with systemic (i.v.) administration of the ET-A receptor antagonist. The local, intragraft treatment improved the mesenteric hemodynamic changes and decreased the accumulation but not the activation of the circulating leukocytes. The structural injury of the graft was prevented in both treated groups. CONCLUSIONS: Endothelins are involved in the hemodynamic events leading to structural injury of the intestinal graft after ischemia-reperfusion. The antagonism of intestinal ET-A receptors by a combination of local and systemic drug delivery offers a rational treatment modality in these conditions.

Animals↗
PubMed1999

Mast cell degranulation prior to ischemia decreases ischemia-reperfusion injury in the canine small intestine.

OBJECTIVE: To determine the impact of previous mast cell degranulation on intestinal ischemia-reperfusion-induced mucosal damaged. MATERIALS: The hemodynamic and morphological consequences of complete arterial occlusion were evaluated in anesthetized dogs. The mast cell degranulator Cremophor-E1 (n = 5) and Compound 48/80 (n = 5) were used to investigate the involvement of gastrointestinal mast cells in ischemia-reperfusion-induced tissue reactions. Seven dogs subjected to complete segmental arterial occlusion served as controls. Intestinal biopsies taken at the end of 120-min ischemia and after 120 min of reperfusion were evaluated histologically. METHODS: The number of mast cells was determined and the degree of mucosal damage was evaluated according to the 5 grade Chiu scale. Mucosal histidine decarboxylase activity was measured in tissue samples and the rate of release of histamine was determined from the venous effluent of the ileal segment. RESULTS: In the control group, 120-min reperfusion significantly increased the plasma histamine level, and induced a severe tissue injury. In the compound 48/80 and Cremophor-E1-pretreated groups, the reduction in the baseline number of mast cells in the villi was 37% and 53%, respectively, and the ischemia-reperfusion-induced release of histamine was significantly decreased. In these groups, the basal mucosal histidine decarboxylase activity was significantly increased and the degree of damage of the intestinal mucosa was significantly reduced. CONCLUSION: It is proposed that mast cell degranulation prior to ischemia may induce a potentially protective mechanism in the small bowel mucosa and decreases ischemia-reperfusion injury in the dog.

Animals↗
PubMed1999

Effects of selective nitric oxide synthase inhibition in hyperdynamic endotoxemia in dogs.

OBJECTIVES: Our aims were to investigate the systemic hemodynamic effects of constitutive endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) inhibitors in hyperdynamic endotoxemia. PATIENTS AND METHODS: Group 1 comprised sham-operated controls, while in group 2, 3 and 4, a hyperdynamic circulatory reaction was elicited by a 2-hour infusion of Escherichia coli endotoxin (ETX) in a dose of 5.3 microg/kg. The animals in group 3 were treated with 12. 5 mg/kg nonselective NOS inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME), and those in group 4 with 2 mg/kg of the specific iNOS inhibitor S-methyl-isothiourea (SMT). Mean arterial pressure (MAP), cardiac output (CO) and myocardial contractility (MC) were measured, and total peripheral resistance (TPR) was calculated. The eNOS and iNOS activities were determined in myocardial biopsy samples taken after 8 h of endotoxemia. RESULTS: ETX induced significant decreases in TPR and MAP, a transient myocardial depression, and increased the myocardial eNOS and iNOS activities. L-NAME decreased the activities of both isoenzymes, increased MC but induced a fall in CO. SMT inhibited iNOS by 60%, without influencing the eNOS activity, increased MAP and contractility in the early phase of endotoxemia, and induced only a slight decrease in CO. CONCLUSIONS: Nonselective NOS inhibition restores the arterial pressure and exerts a positive inotropic effect, but decreases CO. SMT selectively decreases the iNOS activation without disturbing the vasoregulatory function of the eNOS-derived nitric oxide in hyperdynamic endotoxemia in the dog.

Animals↗
PubMed1999

The role of mast cell degranulation in ischaemia-reperfusion-induced mucosal injury in the small intestine.

The role of the intestinal mast cell system in the pathophysiology of postischaemic mucosal lesions is not understood. The present goals were to investigate the contributions of mast cells and mast cell-derived vasoactive mediators to mucosal injury caused by arterial occlusion. We evaluated the intestinal ischaemia-reperfusion-induced local morphological changes in mast cell-depleted anesthetized dogs. Animals subjected to complete segmental intestinal ischaemia and reperfusion served as controls. The selective mucosal-type mast cell degranulator Cremophor-El and the nonselective mast cell depleter Compound 48/80 were used to investigate the involvement of mast cells in reperfusion-induced tissue reactions. Ileal biopsies taken at the end of 120 min of ischaemia and after 120 min of reperfusion were evaluated histologically. The number of mast cells was determined and the degree of mucosal damage was evaluated according to the 0 to 5-grade Chiu scale. Mucosal histidine decarboxylase activity was measured in tissue biopsies and the rate of release of histamine was determined from the venous effluent of the segment. In the control group, 120 min reperfusion induced a severe tissue injury. In the Compound 48/80 and Cremophor-El-pretreated groups, the reduction in the baseline number of mast cells was 37% and 53%, respectively, and the basal mucosal histidine decarboxylase activity was significantly increased. In these groups, the ischaemia-reperfusion-induced release of histamine was significantly decreased, and the degree of damage of the intestinal mucosa was significantly reduced. Mucosal mast cell degranulation plays an important role in the initiation of tissue injury after intestinal ischaemia-reperfusion. Depletion of mast cells prior to ischaemia decreases the severity of mucosal damage, probably in consequence of the stimulation of mucosal histidine decarboxylase activity.

Animals↗
PubMed1998

Endothelin 1 induces leukocyte adhesion in submucosal venules of the rat small intestine.

BACKGROUND & AIMS: The release of endothelin 1 (ET-1) and the activation of leukocytes are involved in the pathophysiology of gastrointestinal ischemia/reperfusion injuries. The aim of this study was to define the in vivo relation between ET-1 and endothelial cell-leukocyte interactions. METHODS: Anesthetized rats were studied to characterize the microvascular effects of increasing doses of local and systemic infusions of ET-1 in all layers of an ileal segment. Leukocyte-endothelial interactions were monitored with intravital fluorescence videomicroscopy. The ETA receptor-selective antagonist BQ 610, the novel ETA-receptor antagonist ETR-PI/fl peptide, and the ETB-receptor antagonist IRL 1038 were used to investigate the roles of receptor subtypes. RESULTS: The functional capillary density of the mucosa was significantly decreased by 3 nmol/kg intravenous ET-1. After 30 minutes the rolling fraction of leukocytes reached 90% in the postcapillary venules, and the number of adherent leukocytes was significantly increased after 90 minutes. ETR-PI/fl peptide inhibited leukocyte rolling by 88%, BQ 610 by 73%, and IRL 1038 by 30%. Both ETA-receptor antagonists prevented ET-1-induced firm adhesion. The ETA-receptor antagonists but not IRL 1038 inhibited the ET-1-induced lymphatic muscle and mucosal capillary perfusion failure. CONCLUSIONS: ET-1 induces leukocyte rolling and adherence through a predominantly ETA receptor-mediated mechanism in the submucosal venules of the intestinal microcirculation.

Animals↗
PubMed1998

Antisense homology box-derived peptides represent a new class of endothelin receptor inhibitors.

Several peptides encoded by the sense and corresponding antisense DNA have been found to recognize and bind to each other. We developed software to search for sense-antisense regions within proteins taking into account the degeneracy of the genetic code, i.e., one amino acid can have several "antisense" counterparts. Using this approach, we searched endothelin receptor type A for intramolecular regions related in sense-antisense fashion. After locating these regions (termed "antisense homology boxes"), several corresponding peptides were synthesized. The four new ET(A) receptor fragment peptides ETR-P1 ("CALSVDRYRAVASW"), ETR-P3 ("QGIGPLITAIEI"), ETR-P4 ("IADNAERYSANLSSHV") and ETR-P6 ("LNRRNGSLRIALSEHLKNRREVA") reported here can inhibit ET-1 activity.

3T3 Cells↗
PubMed1998

Endothelin (ET)-1 induced mucosal damage in the rat small intestine: role of ET(A) receptors.

The role of endothelin (ET)-1 as a mediator of small intestinal mucosal perfusion failure and tissue damage was investigated in the rat using intravital fluorescence videomicroscopy. The effects of intravenous infusion of ET-1 (3 nmol/kg) on functional capillary density, mucosal thickness, and the degree of mucosal damage were evaluated. Administration of ET-1 caused pronounced mucosal injury with a significant reduction of mucosal thickness compared with vehicle-treated control animals. Concomitantly, villous functional capillary density was markedly reduced 30 and 90 min after the infusion of ET-1. ET(A) receptor blockade by pretreatment with BQ 610 or with the novel ET(A) receptor antagonist ETR-P1/FL peptide prevented ET-1 induced capillary perfusion failure and mucosal damage. In contrast, the ET(B) receptor antagonist IRL 1038 was not effective. These results indicate that, acting via the ET(A) receptor, elevated levels of circulating ET-1 under various pathophysiological conditions, such as septic or hemorrhagic shock, might impair nutritive perfusion of the intestinal mucosa and contribute to tissue injury.

Animals↗
PubMed1998

The role of endothelin-1 in circulatory changes during hypodynamic sepsis in the rat.

Our objective was to investigate the significance of endogenous endothelin-1-induced systemic circulatory reactions during hypodynamic sepsis. In the first part of this study, we observed the changes in global hemodynamic parameters in Wistar rats after exogenous endothelin-1 administration in order to test an intervention strategy aimed at preventing the development of hypodynamic cardiovascular derangement during intraabdominal sepsis. Cardiac output, mean arterial blood pressure, and peripheral vascular resistance were recorded, and the endothelin-A receptor antagonist BQ-610 and the endothelin-B receptor antagonist IRL-1038 were used to investigate the role of receptor subtypes in circulatory changes. In addition, the effects of treatment with the novel endothelin-A receptor inhibitor ETR-P1/fl peptide were examined in endothelin-1-treated anesthetized rats. The injection of 1 nmol/kg endothelin-1 induced a significant rise in peripheral vascular resistance, a transient increase in mean arterial pressure, and a decrease in cardiac output. Administration of the endothelin-A receptor antagonist BQ-610 and ETR-P1/fl peptide increased cardiac output and decreased systemic vascular resistance in the controls and in animals treated with exogenous endothelin. In the second part of the study, the animals were instrumented for hemodynamic monitoring and randomized to undergo cecal ligation and perforation for 8 h or control laparotomy. Septic animals with cecal ligation and puncture were normotensive and hypodynamic, with a significantly increased total peripheral resistance throughout the 8 h observation period. ETR-P1/fl peptide treatment started after the induction of sepsis significantly increased cardiac output and decreased systemic vascular resistance almost to control levels. We conclude that endogenous endothelin-1 contributes significantly to the systemic hemodynamic alterations during hypodynamic circulatory response, and the inhibition of endothelin-A receptors may improve global hemodynamic status in this phase of sepsis.

Amino Acid Sequence↗
PubMed1997

Possible relationship between histamine and nitric oxide release in the postischemic flow response following mesenteric ischemia of different durations.

During the postischemic flow response (PFR), vasodilator mediators such as nitric oxide (NO) and histamine are liberated, influencing the blood flow rate at the onset of reperfusion. The possible roles of these two mediators, and the relationship between their release, were examined during segmental intestinal ischemia of different durations and subsequent reperfusion in two series of anesthetized dogs. In series I (untreated ischemia), 15, 30, 60, and 120 min ischemia and 2 h reperfusion were studied. In series II, the same experimental protocol was repeated after pretreatment with the NO synthase inhibitor N-nitro-L-arginine (NNA, 10 mumol/kg, i.e., 2.19 mg/kg). Intramucosal pH (pHi), segmental blood flow and effluent histamine levels were measured, and segmental vascular resistance (SVR) and PFR volumes were calculated. The ischemic periods caused a considerable fall in pHi. Reperfusion resulted in an early return to normal pHi levels following a 15 or 30 min ischemia, but this process took longer after longer occlusions. In the later phase of reperfusion, SVR was elevated. The PFR volume increased in proportion to the duration of occlusion, except after the 120 min ischemia. At the onset of reperfusion, peak histamine levels rose in parallel with the duration of ischemia. During reperfusion, a prolonged decrease in pHi, an increase in SVR, and a reduction in PFR volume, with no significant histamine level elevation, were observed in the NNA-treated groups. This study indicates that both NO and histamine take part in the PFR in the canine small intestine. Inhibition of NO synthesis prevents the postischemic release of histamine.

Animals↗
PubMed1997

The role of mast cells in mucosal permeability changes during ischemia-reperfusion injury of the small intestine.

The objective of this study was to investigate the significance of mast cell-induced reactions in the mucosal functional and morphological alterations induced by 30 min segmental ischemia and 120 min reperfusion in anesthetized dogs. The rates of changes in permeability of the mucosa to sodium fluorescein (NaFL) in the plasma-to-lumen and lumen-to-plasma directions were studied, the local hemodynamics, intramucosal pH (pHi) alterations, mast cell number and degranulation, and degree of tissue injury were determined. The effects of pretreatments with cromolyn (a peritoneal-type mast cell stabilizer), quercetin (a mucosal-type mast cell stabilizer), and dexamethasone (an aspecific membrane stabilizer and mast cell depleter) were evaluated. We found that ischemia-reperfusion induced significant tissue injury, elevated the segmental vascular resistance, and decreased pHi. The plasma-to-lumen clearance of NaFL increased significantly during ischemia and reperfusion. Cromolyn and quercetin pretreatments significantly inhibited the permeability changes, but did not influence the pHi and morphological alterations induced by ischemia-reperfusion. Dexamethasone pretreatment did not influence the number of mast cells, but the degree of mast cell degranulation and fluorescein leakage decreased. We conclude that intestinal mast cells and mast cell-induced reactions contribute to the mucosal permeability alterations during reperfusion, but play only a minor role in ischemia-reperfusion-induced structural injury.

Animals↗
PubMed1997

Effects of antiendothelin treatment on the early hemodynamic changes in hyperdynamic endotoxemia.

We have performed a series of experiments to study the effects of a newly developed antisense homology box-derived endothelin (ET) antagonist peptide (ETR-P1/fl) on the early hemodynamic changes in a hyperdynamic endotoxemic dog model. Mean arterial pressure (MAP), cardiac output (CO) and myocardial contractility (MC) were measured in closed-chest animals. Plasma levels of ET-1,2 were determined by radioimmunassay. A hyperdynamic circulatory response was elicited with a 2-hour infusion of 5.3 micrograms/kg of E. coli endotoxin (ETX). Control and ETX-treated animals received an infusion of ETR-P1/fl (0.1 mg/kg) i.v. ETX treatment decreased MAP and MC, increased initially CO, and a long lasting elevation in the plasma ET level was observed. In ETX-treated animals the administration of ETR-P1/fl significantly prolonged the increase in CO and inhibited the depression of MC. Our results suggest that treatment with the ET antagonist ETR-P1/fl may be advantageous in the early phase of endotoxemia.

Animals↗
PubMed1997

Mucosal permeability changes during intestinal reperfusion injury. The role of mast cells.

The objective of this study was to investigate the role of intestinal mast cells in mucosal functional and morphological alterations induced by 30 min segmental ischemia and 120 min reperfusion in anesthetized dogs. The time course of permeability changes of the mucosa to sodium fluorescein (NaFl) in blood-lumen and lumen-blood directions was studied in two separate series of experiments. Local hemodynamics, intramucosal pH (pHi) alterations, mast cell number and degranulation and the degree of tissue injury were determined. The effects of cromolyn (peritoneal-type mast cell stabilizer), quercetin (mucosal-type mast cell stabilizer), and dexamethasone (aspecific membrane stabilizer and mast cell depleter) pretreatments were evaluated. Ischemia-reperfusion induced significant tissue injury, elevated segmental vascular resistance, and decreased pHi. The blood to lumen clearance of NaFl increased significantly during ischemia and reperfusion. Cromolyn and quercetin pretreatment significantly inhibited permeability changes, but did not influence pHi and morphological alterations induced by ischemia-reperfusion. Dexamethasone pretreatment did not influence the number of mast cells, however, the degree of mast cell degranulation and the degree of mucosal damage decreased. These results demonstrate that mast cells or mast cell-induced reactions contribute to the mucosal permeability alterations and barrier lesions during reperfusion, but play a minor role in reperfusion-induced structural injury.

Animals↗
PubMed1997

Endothelin-1-induced circulatory response in the rat: the role of ETA and ETB receptors.

Production of the powerful vasoconstrictor endothelin-1 (ET1) is increased in a number of pathological conditions. This study was performed 1. to assess the effects of a twofold elevation of circulating ET1 on global hemodynamics and cardiac function, and 2. to determine the ET receptor subtypes that are responsible for this action. We have used the ETA receptor-selective antagonist BQ 610, the novel ETA receptor antagonist ETR-Pl/fl peptide and the specific ETB receptor antagonist IRL 1038 to investigate the role of these receptor subtypes in mediating circulatory changes induced by ET1 in anesthetized Wistar rats. ET1 infusion produced a significant rise in mean arterial pressure (MAP), elevated total peripheral resistance (TPR), and decreased cardiac output (CO). BQ 610 and ETR-Pl/fl pretreatment significantly attenuated the ET1-induced hemodynamic changes. Pretreatment with IRL 1038 had no effect on CO, but significantly reduced MAP and TPR elevation 20 min after ET1 infusion. These results suggest that ET1 may contribute to circulatory failure in conditions with increased ET1 production via a mechanism involving ETA receptors. ETB receptors, albeit to a lesser extent than ETA receptors, are also involved in mediating ET1-induced peripheral vasoconstriction in the rat.

Animals↗
PubMed1996

Effect of nitric oxide synthase inhibition on myocardial contractility in anesthetized normal and endotoxemic dogs.

Nitric oxide (NO) produced by the induced NO synthase (NOS) enzyme has been implicated in the mechanisms of the circulatory changes that occur in the later stages of sepsis. As NO produced by the constitutive form of the enzyme is known to play a role in the regulation of normal circulation, we have performed a series of experiments to study the early circulatory effects of inhibition of NOS in a hyperdynamic endotoxemic dog model. Pentobarbital-anesthetized animals were used. Cardiac output (CO) was measured by thermodilution. Myocardial contractility (MC) was estimated from the slope of the left ventricular end-systolic pressure-diameter relationship obtained from sonomicrometer- and catheter-tip manometer signals in closed chest animals. All animals received a 15 mL/kg/h infusion of Ringer's lactate. A hyperdynamic response was elicited by a 2 h infusion of a total dose of 5.3 micrograms/kg Escherichia coli O55:B5 endotoxin (ETX). CO increased initially by about 25%, and total peripheral resistance decreased by 35%. These changes subsided in 60-90 min, after which a sustained decrease in CO occurred. MC elevated transiently by 25% after the first 30 min of ETX infusion, then decreased gradually below the control level. Administration of 2 mg/kg of the NOS inhibitor N-nitro-L-arginine (NNA) between the 45th and 55th min of the ETX infusion increased MC to the level in the control group, but accelerated the decline of the initially increased CO and caused a sustained increase in total peripheral resistance to about 50% above the control level. In normal (nonendotoxin treated) dogs, NNA also caused a similar increase in MC which, however, lasted at least 3 h. Left ventricular diameter increased in the NNA-treated groups. This increase also occurred in the endotoxin-only group but with a delay of about 2.5 h. Our results demonstrate the participation of constitutive NOS-produced NO in the early hyperdynamic response of endotoxemia. Suppression of NO is associated with increased myocardial contractility. NNA treatment may be favorable for the restoration of depressed cardiac contractility during endotoxemia, but this treatment is probably detrimental for the compensatory systemic flow (CO) increase.

Anesthesia↗
PubMed1996

Comparative study of the circulatory effects of aminoguanidine and N-nitro-L-arginine in hyperdynamic endotoxemia.

We have studied the effects of NG-nitro-L-arginine (NNA) a nitric oxide synthase (NOS) inhibitor, and aminoguanidine (AG) a diamine oxidase inhibitor, on hemodynamic parameters and plasma histamine level using a dog model in which a hyperdynamic circulatory response was elicited with a 2-hour infusion of a low dose (13.75 micrograms/kg) of E. coli 055:B5 endotoxin (ETX). AG (50 mg/kg) or NNA (0.5 mg/kg) was administered intravenously as pretreatment. Hemodynamic variables were studied for 4 hours after the beginning of the ETX infusion. The ETX-elicited hyperdynamic response was abolished by NNA and partially inhibited by AG. AG prevented the increases in cardiac output and heart rate and delayed the early decrease in total peripheral resistance (TPR). The plasma histamine concentration elevation was higher in animals receiving AG than in those receiving only ETX. In the group treated with ETX plus NNA the cardiac output was lower and the TPR was higher than in the ETX plus AG group. In future studies, AG should be considered as one of the possible therapeutic tools in sepsis, as its adverse effect on the compensatory hyperdynamic response is less than that of NOS inhibitors of the L-arginine analog type, while it may favourably influence the deleterious excessive activity of the inducible NOS in the later stages.

Animals↗
PubMed1995

Ischemic time-dependent microvascular changes and reperfusion injury in the rat small intestine.

The significance of the reperfusion period in the pathophysiology of complete occlusion of the intestinal circulation is controversial. Our study was designed to evaluate the exact magnitude of reperfusion-induced intestinal mucosal damage in a standardized rat model of complete segmental arterial ischemia as a function of the occlusion time. Intestinal ischemia was maintained for 15, 30, or 60 min, or ischemia was followed by a 30-min reperfusion period. Intraarterial India ink perfusion was applied to visualize the mucosal vascularity changes induced by ischemia or ischemia-reperfusion. The height of the distributing arterioles of the villi and the average mucosal thickness were recorded by an image analysis system, and the degree of mucosal damage was established on a semiquantitative 0 to 5 grade scale. Ischemia induced erythrocyte obstructions at the villus tip, a progressive decrease in carbon-filled arteriole height, and a concomitant 7, 23, or 35% reduction of the mucosal thickness. The percentage decrease in perfused arteriole height/percentage mucosal thickness reduction ratio was 2.2, 1.5, or 1 during the 15-, 30-, or 60-min ischemia, respectively. Extravasation of the carbon tracer was observed in the 60-min ischemia group. During reperfusion, the mucosal layer was reduced by 27, 38, or 57%, respectively, compared with the baseline values. The arteriole height reduction/mucosal thickness reduction ratio was 1:1 in all ischemic-reperfused groups. The degree of mucosal damage was significantly increased during reperfusion after the 15-min ischemia. Microvessel obstruction is initiated at the villus tip following the onset of arterial occlusion, with subsequent destruction of the surrounding tissues during reperfusion. The reperfusion component of the net mucosal damage may be very significant in early forms of complete occlusion of the mesenteric circulation.

Animals↗
PubMed1995

The antisense homology box: a new motif within proteins that encodes biologically active peptides.

Amphiphilic peptides approximately fifteen amino acids in length and their corresponding antisense peptides exist within protein molecules. These regions (termed antisense homology boxes) are separated by approximately fifty amino acids. Because many sense-antisense peptide pairs have been reported to recognize and bind to each other, antisense homology boxes may be involved in folding, chaperoning and oligomer formation of proteins. The antisense homology box-derived peptide CALSVDRYRAVASW, a fragment of human endothelin A receptor, proved to be a specific inhibitor of endothelin peptide (ET-1) in a smooth muscle relaxation assay. The peptide was able to block endotoxin-induced shock in rats as well. Our finding of endothelin receptor inhibitor among antisense homology box-derived peptides indicates that searching proteins for this new motif may be useful in finding biologically active peptides.

Amino Acid Sequence↗