Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Electrophysiological techniques were used to characterize responses of afferent fibers in pelvic nerve of adult, virgin female rats to mechanical or chemical stimulation of internal reproductive organs and to mechanical stimulation of other pelvic organs. 2. In an in vivo barbiturate-anesthetized preparation, pelvic nerve afferent fibers responded to a wide variety of mechanical stimulation applied to restricted regions of the vaginal canal, caudal uterus (body and cervix), bladder, ureter, colon, or anus. 3. Single-fiber mechanoreceptive fields were invariably confined to a single organ. Notably, responses could be evoked not only by gentle stimulation of the unit's receptive field directly on the organ itself, but also by stimulating the field indirectly with intense stimulation through the appropriate part of a contiguous organ. This innervation feature is consistent with the separability of pelvic organ functions under innocuous conditions but their confusion under noxious ones. 4. Receptive fields on the reproductive organs extended from the caudal edge of the vagina to the uterine body (including the cervix) but were most often located in the fornix (vaginocervical junction). Most units had no or low levels of spontaneous activity. Their responses to mechanical stimuli were usually slowly or moderately adapting and time-locked to the stimulus. 5. Fibers with vaginal receptive fields (including the fornix) responded best either to vaginal distension with a balloon or, more often, to a probe moving along the internal vaginal surface in a direction toward the cervix. They were observed most frequently during the proestrus stage of the rat's estrous cycle. These fibers, therefore, seem particularly suited for relaying information about stimuli that occur during mating. 6. Fibers with receptive fields on the uterine cervix and body responded best to static pressure and were observed less frequently than those with vaginal fields, regardless of estrous stage. They were, however, sensitized by hypoxia. In addition, irritation of the uterus increased the probability of observing them. These fibers, therefore, may exert their primary function during reproductive conditions different from those of virgin rats, such as parturition. 7. Response activity of most of the mechanoreceptive afferent fibers supplying reproductive organs increased as the stimulus intensity increased into the noxious range; i.e., into a range in which the stimulus momentarily produced ischemia at the stimulus site. In addition, in an in vitro preparation, pelvic nerve fibers responded in a dose-dependent manner to injections through the uterine artery of bradykinin (BRAD) as well as to other algesic chemicals, 5-hydroxytryptamine (5-HT) and KCl.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Functional properties of afferent fibers supplying reproductive and other pelvic organs in pelvic nerve of female rat. 231 44

In studies that attempt to measure intracellular calcium [( Ca2+]i) in the intact heart with the calcium indicator indo 1-AM, a fundamental assumption is that the signals report changes in myocyte [Ca2+]i. We studied isolated perfused rabbit hearts loaded with the calcium probe indo 1-AM and recorded surface fluorescence of the left ventricle during continuous excitation at 360 nm. In cells containing indo 1, an increase in [Ca2+]i is associated with an increase in fluorescence intensity at 400 nm, a decrease in intensity at 500 nm, and an increase in the 400:500 nm ratio. Beat-to-beat fluorescence transients were recorded from the surface of the heart coincident with contraction, indicating that a component of the fluorescence signals is derived from beating myocytes. To evaluate the potential contribution of endothelial cells, we compared the response to increases in [Ca2+]o or bradykinin (10(-5) M). In response to an increase of the [Ca2+] in the perfusate from 0.6 to 3.0 mM, left ventricular developed pressure and +dP/dt increased with a simultaneous increase in the [Ca2+]i-sensitive 400:500 nm ratio. Perfusion with the endothelial cell agonist bradykinin caused no change in left ventricular isovolumic peak systolic pressure or left ventricular dP/dt, whereas bradykinin evoked an immediate elevation in both the diastolic and systolic levels of the [Ca2+]i-sensitive 400:500 nm ratio. In additional experiments with indo 1-loaded isolated beating myocytes, superfusion with bradykinin had no effect on either the fluorescence [Ca2+]i transients or contractility. In contrast, superfusion of indo 1-loaded cultured endothelial cells with bradykinin caused the elevation of [Ca2+]i within seconds. Fluorescence microscopy of unstained frozen tissue sections from indo 1-loaded hearts also suggested the presence of more intense microvascular endothelial cell indo 1 fluorescence relative to that observed in myocytes. These experiments provide evidence that a component of [Ca2+]i-sensitive fluorescence of whole hearts loaded with indo 1 is contributed by nonmyocyte sources, including endothelial cells. These results also raise the caution that the abrupt rise of [Ca2+]i that has been observed during the initial phase of ischemia in whole hearts loaded with indo 1 may be partly derived from endothelial cells rather than myocytes.
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PMID:Contribution of endothelial cells to calcium-dependent fluorescence transients in rabbit hearts loaded with indo 1. 237 80

Intracellular calcium transients were studied prior, during and after 30 min of global ischemia in control and aortic constricted rat hearts, with and without acute treatment with verapamil. Calcium transients [Ca2+]i continued to occur in verapamil treated animals for 18-20 min following the onset of global ischemia, whereas untreated hearts demonstrated calcium transients for only 3-8 min following global ischemia. Following the onset of global ischemia calcium transients continued to occur even though there was no measurable developed pressure. When calcium transients occurred for shorter periods of time during global ischemia the rise in diastolic calcium was greater and recovery was less. Addition of bradykinin to the perfusate showed that an increase in diastolic [Ca2+]i was related to a decrease in amplitude of developed [Ca2+]i transients and a decrease in developed pressure, but not to a change in coronary flow.
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PMID:Influence of ischemia on [Ca2+]i transients following drug therapy in hearts from aortic constricted rats. 239 2

Local chemical factors, such as H+, K+, Ca2+, adenosine, and osmolarity, affect cerebral resistance vessels. Their participation in the regulation of cerebral blood flow is suggested by changes in their concentration in the interstitial space during increased neuronal activity, strong hypoxia, and transient of incomplete ischemia. Such changes are not observed during autoregulation. Possible interactions between several factors must be considered when estimating their role. Autonomic nerves innervating cerebral vessels include: sympathetic nerves releasing the constrictor transmitter noradrenaline; parasympathetic nerves (liberating the dilator transmitter acetylcholine) and other dilator fibers (containing either serotonin, substance P, or vasoactive intestinal polypeptide). Participation of these systems in the adjustment of cerebral blood flow is still a matter of discussion, except for the protective effect of sympathetic nerves on the upper limit of autoregulation and on the blood--brain barrier. Humoral compounds, generated and released within the brain, which can affect cerebral blood flow include: histamine, bradykinin, and prostaglandins. Histamine, bradykinin, prostaglandin E2, and prostacyclin dilate cerebral arteries in situ, while prostaglandin F2 alpha reduces cerebral blood flow. Histamine and bradykinin alter the permeability of the blood--brain barrier and might be involved in pathological events, such as edema.
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PMID:Local chemical, neural, and humoral regulation of cerebrovascular resistance vessels. 240 98

We have noted, recently, that early after experimental intestinal ischemia, endotoxemia or whole-body trauma in rats, that the endothelial cells (EC) lining splanchnic precapillary microvessels (i.e., arterioles and metarterioles) appear to be contorted, often exhibit swelling and appear to have lost a great deal of their normal wetable surfaces as evidenced by sticking of white blood cells and platelets. Using identical circulatory shock and trauma models, we now report that irrespective of the ischemic or traumatic etiology, neither of four vasodilators, e.g., acetylcholine, bradykinin, substance P or histamine, were able to elicit much in the way of vasodilatation of metarterioles (10-12 microns in size) early after induction of intestinal ischemia, endotoxemia or whole-body trauma. Irrespective of the mechanism(s), if our results are seen in other organ regions as well, the end result would be a severe reduction in lumen sizes of the microscopic resistance and capacitance vessels in the lung ("shock lung"), kidneys, liver, etc., resulting in multiple organ failure.
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PMID:Failure of microscopic metarterioles to elicit vasodilator responses to acetylcholine, bradykinin, histamine and substance P after ischemic shock, endotoxemia and trauma: possible role of endothelial cells. 242 37

Components of the renin-angiotensin system (RAS) have been found in heart tissue and it is likely that angiotensin II (ANG II) is generated locally in the heart as in other organs. Pharmacological interference with converting enzyme (CE) inhibitors reduced CE activity and ANG II generation in the heart. To investigate whether local inhibition of CE in the heart with the CE inhibitor ramipril might contribute to the therapeutic effects, experiments were performed in isolated perfused working rat hearts. Acute regional myocardial ischemia was induced by occlusion of the left coronary artery followed by reperfusion. In ischemic isolated rat hearts, both single oral pretreatment with ramipril (1 mg/kg) or perfusion with the active moiety, ramiprilat (10 micrograms/ml), protected against ventricular fibrillation, which invariably occurred in control hearts during reperfusion. Reperfusion arrhythmias were aggravated by perfusion with ANG I and ANG II, but prevented by bradykinin. ANG I-enhanced ventricular fibrillations were completely eliminated during local CE inhibition with ramipril. The CE inhibitor also improved cardiodynamics. Coronary flow, left ventricular pressure, dp/dtmax, and myocardial oxygen consumption were increased in comparison to controls without changes in heart rate. In the perfusate of treated hearts, lactate dehydrogenase, and creatine kinase activities and lactate production, were reduced. Myocardial tissue levels of glycogen, ATP, and creatine phosphate were increased in ramipril-pretreated hearts whereas lactate was decreased. The results of these experiments in rat hearts suggest that local inhibition of CE by ramipril exerts protective effects after ischemia and reperfusion by reducing arrhythmias and improving cardiac function and metabolism, thus probably contributing to the therapeutic effects of CE inhibitors in cardiovascular diseases.
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PMID:Beneficial effects of the converting enzyme inhibitor, ramipril, in ischemic rat hearts. 243 98

In order to further elucidate the mechanisms involved in therapeutic effects of prostacyclin and Iloprost in peripheral ischemic disease, the actions on microvascular tone, capillary density, and increases in venular permeability induced by inflammatory mediators and by ischemia were investigated in the cheek pouch of anaesthetized Syrian hamsters using intravital videomicroscopy and--for quantification of vascular permeability--venular leakage of fluorescein-labelled dextran (FITC-D; Mw 70,000). Iloprost at the nonhypotensive, platelet aggregation-inhibiting dose of 0.5 microgram/kg/min i.v. significantly increased the diameters of arterioles and venules and the density of perfused capillaries and antagonized vasoconstriction and decrease of perfused capillary density as induced by Leukotriene D4 (LTD4; 10(-7) M). Iloprost significantly antagonized venular leakage of FITC-D induced by histamine (10(-5) M), serotonin (10(-5) M), bradykinin (10(-6) M) and reperfusion after 30 min ischemia. Topical application of Iloprost (10(-8) M), intraarterial infusion of Prostaglandin E1 (PGE1; 2.0 micrograms/kg/min), and topical Forskolin (10(-5) M) also attenuated histamine-induced venular FITC-D leakage, while topical PGE1 (10(-7) M) and i.v. infusion of Nifedipine (30 micrograms/kg + 10 micrograms/kg/min) were not effective. It is concluded, that microvascular effects of Iloprost by improvement of tissue perfusion and functional antagonism of mediator-induced tissue edema and vasospasm could contribute to therapeutic effectiveness in ischemic diseases.
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PMID:Action of the stable prostacyclin analogue iloprost on microvascular tone and -permeability in the hamster cheek pouch. 244 31

1. In the present three-part study electrophysiological techniques were used to characterize responses of afferent fibers in the rat hypogastric nerve to mechanical or chemical stimulation of the uterus, and anatomical techniques were used to identify the spinal segments through which uterine afferent fibers enter the spinal cord. 2. In an in vivo barbiturate-anesthetized preparation, hypogastric afferent fibers responded in a time-locked manner to mechanical stimulation confined to restricted regions of the uterus and adjacent ligament. Receptive fields were most often located on the uterine body, particularly over the cervix. The few located on the uterine horn were usually near regions irritated during preparative surgery. Effective mechanical stimuli (pressure, stretching, squeezing, probing, rarely contractions) were typically greater than 5 g and simultaneously accompanied by transient ischemia around the probe or contracted area. Distension, unless extreme, was not an effective stimulus. Retrospective analysis of the data indicated that fibers may be more sensitive to uterine stimulation when rats are in vaginal estrus/proestrus than in diestrus/metestrus. 3. In an in vitro preparation, hypogastric afferent fibers responded in a dose-dependent fashion to injections into the uterine artery of the algesic chemicals bradykinin, 5-hydroxytryptamine, and KCl. They also responded to high doses of CO2 (in saline) and NaCN, but rarely to lower doses. Nearly all fibers responded to more than one chemical with response characteristics unique to each chemical (e.g., latency, duration, peak rate). 4. Injections of horseradish peroxidase into the uterine body and small portions of the adjacent horns in rats in vaginal estrus consistently labeled a small number of cells in the L1-S1 dorsal root ganglia, with peaks at L2 and L6. Virtually no cells were labeled in rats whose estrous cycle had been disrupted (by inadvertently keeping them in constant light conditions for several weeks). 5. These results indicate that uterine afferent fibers travel to the central nervous system through both the hypogastric (e.g., L1-L4 ganglia) and pelvic (e.g., L5-S1 ganglia) nerves in the rat, and that hypogastric fibers are capable of conveying fairly precise information about temporal and spatial aspects of uterine mechanical and chemical stimulation. The results also encourage future research into the possibility that the responses of these fibers vary as a function of estrous stage or other aspects of the condition of the uterus (e.g., its irritation).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Afferent fibers supplying the uterus in the rat. 244 20

Biochemical, pharmacological, and molecular biological data provide evidence for the presence of a cardiac renin-angiotensin system. Tissue angiotensins were demonstrated in all regions of the mammalian heart. Reduction of cardiac angiotensin II formation after oral administration of converting enzyme (CE) inhibitors in nephrectomized animals points to local generation of these peptides. Functional studies in isolated working rat hearts subjected to transient regional ischemia and reperfusion showed that there is aggravation of arrhythmias as well as exhaustion of energy status by angiotensins. This was prevented by CE inhibition and/or perfusion with bradykinin (BK), which in turn could be competitively antagonized with a BK antagonist. Intracoronary infusion of low-dose bradykinin attenuated ischemia-reperfusion injuries and reduced enzyme and lactate release in anesthetized dogs. Oral pretreatment with the CE inhibitor ramipril in rats, in doses that did not affect the elevation of blood pressure caused by aortic constriction, could prevent induction of as well as cause regression of established cardiac hypertrophy. In contrast, pure vasodilation was without effect on cardiac enlargement despite lowering blood pressure, pointing to a possible trophic influence of angiotensin II. Thus, apart from afterload reduction and euvolumia produced by CE inhibition, the outstanding efficacy of this therapeutic approach in congestive heart failure and cardiac hypertrophy and its potential usefulness in myocardial ischemia may also be explained by intracardiac suppression of angiotensin II generation and bradykinin degradation.
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PMID:Pharmacological interference with the cardiac renin-angiotensin system. 248 22

We studied the in vivo effects of Daflon 500 mg on transvascular movement of macromolecules induced by bradykinin (BK) and ischemia. The experimental preparation involved the rat cremaster muscle. The muscle was fashioned as a single bag (new procedure), placed in a transparent chamber and superfused with a bicarbonate buffer solution equilibrated with a 5% CO2 95% N2 gas mixture in order to obtain pH 7.40, PCO2 = 40 mmHg, PO2 = 20-40 mmHg and thermostated at 35 degrees C. FITC-Dextran 150 (MW 150,000) was injected i.v. as a macromolecular tracer. BK was added to the buffer solution at the concentration of 2 micrograms/ml five minutes after a control period of 60 minutes. Ischemia was performed during 60 min by a clamp positioned on the main artery of the cremaster muscle. Animals treated with Daflon 500 mg (100 mg/kg) 18 and 2 hours before experiments showed a significant reduction in FITC-Dextran 150 leakage in both BK and ischemia protocols. Leakage of FITC-Dextran 150 started 2-3 min after application of BK in the two animal groups but the response was less important (+ 270%) and the preparation returned to control appearance after 40 min in the treated rats in contrast with control rats (+ 450% and 70 min). The amplitude of FITC-Dextran 150 leakage was identical just one hour after ischemia in the two animal groups, but microvascular permeability returned to basal state in treated animals (30 min), a fact non observed in non treated animals. These data demonstrate the protective effect of Daflon 500 mg on the microvascular muscle network in vivo.
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PMID:Daflon 500 mg depresses bradykinin-ischemia-induced microvascular leakage of FITC dextran in rat cremaster muscle. 248 28


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